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PRACTICE PEARLSInsight on

medical barriersto weight loss

MEDICAL UPDATE ON WEIGHT MANAGEMENT

PRACTICE PEARLSInsight on

medical barriersto weight loss Treating obesity

with a tailored approach

CONQUERING AN OBESOGENIC ENVIRONMENT

WeightManagement_Saxenda_Fall2018_5PAGEAD.indd 1 8/16/18 1:43 PM

MEDICAL UPDATE ON WEIGHT MANAGEMENT

TABLE OF CONTENTS 3 Treating overweight and obesity

with a patient-centered approach How tailoring a patient’s weight-loss plan can improve outcomes

8 Overcoming medical barriers to weight lossFrom hormonal disorders to obstructive sleep apnea, experts explain how to manage the conditions that can interfere with weight loss

17 Helping patients conquer an obesogenic environmentTechniques to avoid the everyday situations that entice people to eat more and move less

20 Case studiesInsight on managing patients who have regained their initial weight loss

22 Expert Q&AExploring the role of pharmacotherapy

24 Office screening toolEvaluating patients for obesity treatment

Obesity treatment: Improving outcomes with a patient-centered approach

2 HEALTH MONITOR MEDICAL UPDATE

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❖ M O D E L O F C A R E

Obesity treatment: Improving outcomes with a patient-centered approach

goals rather than health-related improvements. “A lot of patients think they need to achieve a ‘normal’ body weight, which is not a real-istic goal for many people with obesity,” says Elise Brett, MD, an endocrinologist and asso-ciate clinical professor at the Icahn School of Medicine at Mount Sinai in New York City and coauthor of the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) guidelines for the medical care of patients with obesity.2

A goal of reducing body weight by 5% to 10% is appropriate for most patients, says Dr. Brett. The health benefits of this more-attainable weight loss are well documented (see Table 1 on p. 5). For example, in the Diabetes Prevention Program (DPP) a median weight loss of 5.5% body weight achieved and maintained for almost three years reduced the likelihood of a patient converting from prediabetes to type 2 diabetes by 58%.3

Likewise, the Look AHEAD trial reported that losing 10% of body weight over one year reduced the risk for cardiovascular events (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hos-pitalization for angina) by 21%.4 Therefore, it’s important to guide patients toward goals that are based on improving comorbidities, physical functioning and overall quality of life. Points to keep in mind: • Manage expectations and discuss plateaus.

Even a successful weight-reduction effort will reach a plateau eventually as physiolog-ic adaptations and psychosocial challenges

3

P atients with overweight and obesity present a clinical challenge, but there’s abundant scientific evidence that a

well-crafted plan for weight reduction and maintenance can dramatically reduce their risk for a range of chronic diseases. Research also makes clear that no single approach to obesity treatment works for everyone. Tailoring therapy is essential, as is perse-verance in finding a treatment plan that works. “We can’t get discouraged,” empha-sizes George Bray, MD, endocrinologist at the Pennington Biomedical Research Center of Louisiana State University in Baton Rouge and lead author for The Endocrine Society’s 2018 scientific statement on obesity manage-ment.1 “We have to keep plugging away to help these patients.”

The good news: With an array of evidence-based treatments available—from lifestyle and behavioral therapy to weight-loss medications and surgery—you have numerous options to help patients achieve their goals and mini-mize the risk of weight-related complications. The first step in devising a plan: Establish the patient’s severity of obesity (see Figure 1 on p. 4). Based on this classification, consider the following treatment strategies, taking into account your patient’s medical history, psy-chosocial needs and individual preferences.

1. Individualize goals. Patients who start weight-loss treatment are often overly ambitious, striving for cosmetic


make it difficult to drop more pounds. Plateaus can leave patients disappointed to the point of abandoning their weight-loss efforts, cautions Dr. Bray, particularly if they have out-of-pocket costs associated with treatment, such as a gym membership or medication co-pay. When this happens, reinforce the positive health benefits of maintaining their weight loss.

• Encourage self-monitoring and regular follow-up. Studies indicate that patients who keep food diaries and track activity levels are more likely to achieve and maintain weight-loss goals.1 Also, treatment efficacy should be evaluated early. AACE guidelines recommend that patients should strive for at least a 2.5% loss of body weight in the first month after making behavioral and lifestyle changes.2 If a patient has not met that goal, try another approach.

2. Help patients choose a realistic eating plan. Fad diets usually limit or emphasize specific macronutrients. “But it’s not the macronu-trients that make the most difference,” notes Dr. Bray, who was a principal investigator for several landmark weight-reduction trials. “It’s the calories.” A 2009 study by Dr. Bray and col-leagues found that overweight adults randomly assigned to eat one of four calorie-reduced diets with varying levels of carbs, fat and protein all lost about 7% of body weight, on average, after six months. Most later regained some of the weight, but there was no difference between the four groups.5

The AACE guidelines recommend a meal plan that creates a deficit of 500 to 750 calories daily. A registered dietitian can help patients set daily goals for caloric intake and design specific meal plans. In addition, reduced-calorie diets are more likely to succeed if you take the following steps:• Build on what they already eat. A patient’s

personal and cultural preferences should be considered when choosing a meal plan. For

example, the Mediterranean diet, which is rich in plant foods, limits meat and replaces butter with olive oil, has been proven effective for weight loss. However, research suggests this depends on the patient: Participants whose baseline diets were dramatically different from the Mediterranean diet were less likely to lose weight because their adherence was low.6 The takeaway: Ask what patients usually eat on an average day and discuss if it’s easier for them to cut food portions versus cutting out certain foods entirely.

• Encourage healthy choices. “Eating more fruits and vegetables increases bulk in the diet, so patients feel more full,” notes Dr. Brett. Increased satiety leaves less room for unhealthy choices such as foods high in sugar, saturated fat and trans fat.

• Consider increasing protein intake. Calories are king, says Dr. Brett, but high-protein foods (e.g., fish, skinless chicken and lean meats) induce satiety, resulting in consump-tion of fewer calories. Moreover, people who eat a low-protein diet store slightly more body fat than those who consume higher levels, says Dr. Bray, noting that a healthy diet can include up to one quarter of calories from protein. One caveat: Certain popular diets recommend protein consumption that exceeds 25% of calories, which should be avoided in patients with renal dysfunction.

• Take advantage of technology. Using a smart-phone app to record all calories can help patients stay on track. When they have to take note of every morsel consumed, says Dr. Brett, “it might deter them from eating that cookie.” She recommends the apps Lose It! and MyFitnessPal.

3. Discuss the benefits of physical activity. Caloric restriction is essential for eliminating excess body fat, but patients who also adopt regular exercise regimens have the best chance of maintaining long-term weight loss, according to the findings of the Diabetes Prevention Program,



Figure 1. Weight management based on a complications-centric approach1

SCREENING CRITERIA• BMI

– Overweight = BMI 25 to <30 kg/m2 – Obese = BMI ≥30 kg/m2

• Abdominal obesity – Waist circumference: ≥40 inches for men, ≥35 inches for women

• Physical exam, review of systems, lab tests

STAGING AND TREATMENTNormal weight: BMI <25Requires prevention (healthy eating, physical activity, sleep hygiene)

Stage 0 obesity: BMI ≥25 with no complications Lifestyle/behavioral therapy (clinician/RD counseling, web/remote program, structured multidisciplinary program); may consider weight-loss medication based on risk factors/severity of obesity

Stage 1 obesity: BMI ≥25 with mild to moderate complication(s)Lifestyle/behavioral therapy, weight-loss medication as indicated

Stage 2 obesity: BMI ≥25 with severe complication(s)Lifestyle/behavioral therapy, weight-loss medication as indicated

BMI ≥35: Consider bariatric surgery with weight-related complication(s)

Note: Weight-related complications include hypertension, hyperlipidemia, obstructive sleep apnea, etc. See AACE guidelines for more details.


make it difficult to drop more pounds. Plateaus can leave patients disappointed to the point of abandoning their weight-loss efforts, cautions Dr. Bray, particularly if they have out-of-pocket costs associated with treatment, such as a gym membership or medication co-pay. When this happens, reinforce the positive health benefits of maintaining their weight loss.

• Encourage self-monitoring and regular follow-up. Studies indicate that patients who keep food diaries and track activity levels are more likely to achieve and maintain weight-loss goals.1 Also, treatment efficacy should be evaluated early. AACE guidelines recommend that patients should strive for at least a 2.5% loss of body weight in the first month after making behavioral and lifestyle changes.2 If a patient has not met that goal, try another approach.

2. Help patients choose a realistic eating plan. Fad diets usually limit or emphasize specific macronutrients. “But it’s not the macronu-trients that make the most difference,” notes Dr. Bray, who was a principal investigator for several landmark weight-reduction trials. “It’s the calories.” A 2009 study by Dr. Bray and col-leagues found that overweight adults randomly assigned to eat one of four calorie-reduced diets with varying levels of carbs, fat and protein all lost about 7% of body weight, on average, after six months. Most later regained some of the weight, but there was no difference between the four groups.5

The AACE guidelines recommend a meal plan that creates a deficit of 500 to 750 calories daily. A registered dietitian can help patients set daily goals for caloric intake and design specific meal plans. In addition, reduced-calorie diets are more likely to succeed if you take the following steps:• Build on what they already eat. A patient’s

personal and cultural preferences should be considered when choosing a meal plan. For

example, the Mediterranean diet, which is rich in plant foods, limits meat and replaces butter with olive oil, has been proven effective for weight loss. However, research suggests this depends on the patient: Participants whose baseline diets were dramatically different from the Mediterranean diet were less likely to lose weight because their adherence was low.6 The takeaway: Ask what patients usually eat on an average day and discuss if it’s easier for them to cut food portions versus cutting out certain foods entirely.

• Encourage healthy choices. “Eating more fruits and vegetables increases bulk in the diet, so patients feel more full,” notes Dr. Brett. Increased satiety leaves less room for unhealthy choices such as foods high in sugar, saturated fat and trans fat.

• Consider increasing protein intake. Calories are king, says Dr. Brett, but high-protein foods (e.g., fish, skinless chicken and lean meats) induce satiety, resulting in consump-tion of fewer calories. Moreover, people who eat a low-protein diet store slightly more body fat than those who consume higher levels, says Dr. Bray, noting that a healthy diet can include up to one quarter of calories from protein. One caveat: Certain popular diets recommend protein consumption that exceeds 25% of calories, which should be avoided in patients with renal dysfunction.

• Take advantage of technology. Using a smart-phone app to record all calories can help patients stay on track. When they have to take note of every morsel consumed, says Dr. Brett, “it might deter them from eating that cookie.” She recommends the apps Lose It! and MyFitnessPal.

3. Discuss the benefits of physical activity. Caloric restriction is essential for eliminating excess body fat, but patients who also adopt regular exercise regimens have the best chance of maintaining long-term weight loss, according to the findings of the Diabetes Prevention Program,


Look AHEAD and other studies. And of course, many health parameters improve with increased physical activity regardless of pounds lost (e.g., decreased blood pressure and decreased triglycerides, improved glucose tolerance). Beginning an exercise program is often a struggle for patients, but work-outs become easier once they have lost a few pounds, notes Dr. Bray. Considerations to keep in mind: • Start simple. For patients who have been

physically inactive, Dr. Bray recommends 30 minutes of walking at least three days a week as a good initial goal, but any amount the patient can commit to is helpful.

• Encourage use of a pedometer, and advise them to aim for 10,000 steps a day. A recent meta-analysis concluded that in patients with overweight and obesity, participants who wore a pedometer increased their steps by about one mile a day compared with those who did not use a pedometer.7

• Suggest strength training. Resistance exer-cise with machines, free weights or exercise

5

ComplicationProportion of weight loss

needed to achieve therapeutic benefits

Diabetes prevention 3% to 10%

Hypertension 5% to >15%

Dyslipidemia 3% to >15%

Elevated A1C 3% to >15%

Nonalcoholic fatty liver disease 10%

Sleep apnea 10%

Osteoarthritis 5% to 10%

Stress incontinence 5% to 10%

Gastroesophageal reflux disease

5% to 10%

Polycystic ovary syndrome 5% to 15% (>10% optimal to treat anovulation)

Table 1. The health benefits of modest weight loss2,9



bands improves muscle tone and appears to promote fat loss by increasing resting met-abolic rate.1 AACE guidelines recommend that patients engage in a training regimen that targets all major muscle groups two to three times per week, performing one set of each exercise. Working with a fitness trainer can help prevent injury and get the best results.

4. Add pharmacotherapy to lifestyle changes as needed. “Patients have to fight against the physi-ologic mechanisms that lead to weight gain,” notes W. Timothy Garvey, MD, professor and chair of the department of nutrition sciences at the University of Alabama, Birmingham, and lead author of the AACE obesity management guide-lines. “We shouldn’t be afraid of prescrib-ing interventions that counteract those pathways.” Unfortunately, a 2018 study found that 81% of primary care physi-cians surveyed do not offer weight-loss medications to their patients with obesity.8 The reason, suggests Dr. Brett: The broader medical community has not fully embraced the idea that obesity is a chronic disease, with many clinicians (and patients) con-tinuing to believe that a failure of willpower is to blame for weight gain. What’s more, she believes that the market withdrawal of older obesity drugs may be responsible

for some clinicians’ reluctance to prescribe weight-loss medications. Yet the latest medi-cations approved for long-term treatment of obesity have good safety records, and studies consistently indicate that combining pharma-cotherapy with lifestyle changes can increase a patient’s chances of attaining a weight-loss goal, says Dr. Brett.

There are five medications indicated for long-term treatment in patients with a BMI ≥30 kg/m2 or ≥27 kg/m2 with at least one weight-related complication. Options include liraglutide (3-mg daily dose), lorcaserin, naltrexone/bupropion sustained release, orlistat and phentermine/topiramate extend-ed release. A number of older appetite sup-pressants (e.g., phentermine monotherapy) are approved for short-term use (less than 12 weeks).2 The following strategies can help your patients gain the most benefit from pharmacotherapy:• Consider the patient’s medical history and

current medication regimen. When decid-ing on which weight-loss medication to prescribe, start by reviewing the drug’s con-traindications and precautions, which may rule out certain options, notes Dr. Bray. For example, a patient with hypertension may not be a good candidate for weight-loss medications associated with increases in blood pressure.

• Monitor response closely. “Don’t put someone on a medication and let them

“You have to tailor weight-loss treatment and monitor the patient to see if he or she actually responds.” —George Bray, MD


7

REFERENCES1. Bray GA, et al. The Science of Obesity Management: An Endocrine Society Scientific

Statement. Endocr Rev. 2018;39(2):79-132.

2. Garvey WT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr Pract. 2016;22(suppl 3):1-203.

3. Knowler WC, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677-1686.

4. Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol. 2016;4(11):913-921.

5. Sacks FM, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360:859-73.

6. Beunza JJ, et al Adherence to the Mediterranean diet, long-term weight change, and incident overweight or obesity. Am J Clin Nutr. 2010;92(6):1484-1493.

7. Schock D, et al. Do pedometers increase activity and improve health outcomes? J Fam Pract. 2017;66(1):48-53.

8. Simon R, et al. Provider practice habits and barriers to care in obesity management in a large multicenter health system. Endocr Pract. 2018;24(4):321-328.

9. Daniel S, et al. A complications-based clinical staging of obesity to guide treatment modality and intensity. Curr Opin Endocrinol Diabetes Obes. 2013;20(5):377-388.


for some clinicians’ reluctance to prescribe weight-loss medications. Yet the latest medi-cations approved for long-term treatment of obesity have good safety records, and studies consistently indicate that combining pharma-cotherapy with lifestyle changes can increase a patient’s chances of attaining a weight-loss goal, says Dr. Brett.

There are five medications indicated for long-term treatment in patients with a BMI ≥30 kg/m2 or ≥27 kg/m2 with at least one weight-related complication. Options include liraglutide (3-mg daily dose), lorcaserin, naltrexone/bupropion sustained release, orlistat and phentermine/topiramate extend-ed release. A number of older appetite sup-pressants (e.g., phentermine monotherapy) are approved for short-term use (less than 12 weeks).2 The following strategies can help your patients gain the most benefit from pharmacotherapy:• Consider the patient’s medical history and

current medication regimen. When decid-ing on which weight-loss medication to prescribe, start by reviewing the drug’s con-traindications and precautions, which may rule out certain options, notes Dr. Bray. For example, a patient with hypertension may not be a good candidate for weight-loss medications associated with increases in blood pressure.

• Monitor response closely. “Don’t put someone on a medication and let them

go,” says Dr. Bray. “You have to monitor the patient and see if he or she actually responds.” In general, if a patient does not lose at least 5% of their body weight with-in three months of starting the medica-tion, consider switching to another one—patients who don’t benefit from an initial obesity drug frequently respond well to a second choice, notes Dr. Bray.

• Be persistent. Trial and error may be neces-sary to find a medication that aids weight loss without intolerable side effects. “If one causes side effects, that doesn’t mean another one will,” says Dr. Brett, as each of the five weight-loss medications for long-term use has a different mechanism of action.

5. Consider bariatric surgery for certain patients.Each year, U.S. surgeons perform roughly 200,000 bariatric procedures, which are a prov-en intervention to induce weight loss for severe

obesity, defined as a BMI ≥40 or a BMI ≥35 (or ≥30 for laparoscopic gastric banding) with at least one obesity-related complication. Two points that are important to keep in mind when discussing surgery with patients:• Be sure they understand that dietary chang-

es are mandatory. “Surgery isn’t magic,” says Dr. Garvey. “There can be complications and weight regain. A person must continue to follow lifestyle changes, and the proce-dure requires lifelong medical follow-up.”

• Get family members involved to increase the odds of success. Dr. Bray notes that it is also important to ensure that a patient’s family will support their decision to have the procedure and help them follow the strict dietary plan the patient must follow after-ward. In addition, it is helpful if family mem-bers—especially the person who does most of the cooking—improve their own eating habits to make dietary adherence easier for the patient. —Timothy Gower


❖ P R A C T I C E P E A R L S

Cardiovascular and pulmonary diseases. Patients with asthma, heart failure, chronic obstructive pulmonary disease or angina can become tired or short of breath after a few min-utes of activity. Also, exercise can trigger symp-toms for patients with certain types of asthma.

Irritable bowel syndrome (IBS). Fear of diarrhea can discourage patients with IBS from enjoying walks or other outdoor exercise, Dr. Greenway notes. In addition, bloating, flatu-lence and other abdominal symptoms can prompt patients to avoid certain foods, such as high-fiber cereals and beans, making healthy eating more difficult.

Depression is common in patients with over-weight and obesity.1,6 “A person who is feel-ing depressed will have trouble finding the motivation to do all the hard work involved with losing weight and keeping it off,” says Ethan Lazarus, MD, director of the Clinical Nutrition Center in Denver and vice president of the Obesity Medicine Association. Indeed, symptoms such as fatigue, low energy, poor sleep and overeating often go hand in hand with depression.

Medication side effects. Certain anticon-vulsants, mood stabilizers, corticosteroids and other types of medication can cause weight gain, either by stimulating appetite, slowing metabolism or changing how the body stores glucose and other nutrients.8

Identifying medical issuesPrompt detection of weight-related comorbidi-ties is crucial, both to starting treatment of the illness and getting weight loss back on track. The following can point toward a diagnosis or suggest the need for further testing:

The workupAll patients with overweight/obesity should have an annual physical exam, says Dr. Lazarus, which is often the first step in diag-

Overcoming medical barriers to weight loss


W hen a patient can’t lose weight despite several attempts, it can be frustrating for both you and

the patient. One issue could be the patient’s own unawareness of certain behaviors, such as miscalculating portion sizes. Yet there’s another likely culprit: A comorbid medical condition may be thwarting their efforts. “If you don’t address the underlying physiologic issue that is causing obesity, it’s unlikely that a weight-loss program will be successful over the long term,” says Frank Greenway, MD, professor and chief medical officer at Pennington Biomedical Research Center at Louisiana State University.

What’s more, carrying excess weight increas-es the risk of developing problems such as glucose intolerance, type 2 diabetes, osteoarthri-tis, nonalcoholic fatty liver disease and depres-sion.1-6 These conditions can alter metabolism and/or result in symptoms (e.g., pain, fatigue, trouble sleeping) that interfere with the patient’s ability to make the necessary lifestyle changes to lose weight. This creates a vicious cycle: Their comorbidity leads to weight gain, which in turn may worsen their comorbidity and hamper their ability to follow a weight-loss plan.

Common weight-related complicationsDr. Greenway urges providers to suspect a comorbid illness in any patient with over-weight (BMI ≥25) or obesity (BMI ≥30), echoing the clinical practice guidelines from the American Association of Clinical Endocrinologists (AACE) for treating patients with obesity.7 The following diseas-

es can be associated with weight gain and/or interfere with a weight-loss program:

Type 2 diabetes. Insulin resistance alters glu-cose and lipid metabolism and promotes fat cell storage. Also, some classes of antihyperglyce-mics, such as sulfonylureas, thiazolidinediones and insulin, can cause weight gain.

Hypothyroidism. Low levels of thyroid hor-mone can slow metabolism.

Polycystic ovary syndrome (PCOS). This condition, marked by elevated androgen levels, irregular periods and/or multiple ovarian cysts, afflicts 1 in 10 women of childbearing age. A common symptom is weight gain that is not caused by excessive eating; others include acne, excessive facial hair, thinning hair and diffi-culty getting pregnant.

Obstructive sleep apnea (OSA) and other sleep issues. The breathing interruptions typical of OSA can leave patients sleep-deprived, inattentive, less able to manage their behavior and less motivated to exercise or eat properly, Dr. Greenway says. Further, sleep deprivation raises cortisol and decreas-es leptin, leading to metabolic changes that increase appetite and promote weight gain.

Chronic pain due to arthritis and other conditions makes exercise difficult. “Pain is a strong physiologic deterrent,” Dr. Greenway says. “Patients think about the pain and not the reasons for losing weight.” Plus, the result-ing immobility reduces muscle mass and aero-bic fitness, further deterring activity.


Complication Identification based on information available in initial evaluation

Metabolic syndrome Waist circumference, blood pressure, triglycerides, HDL cholesterol, fasting glucose (presence of 3 or more)

Prediabetes Fasting glucose

Type 2 diabetes Fasting glucose

Dyslipidemia Fasting triglycerides and HDL with lipid panel

Hypertension Systolic and diastolic sitting blood pressures

Nonalcoholic fatty liver disease

Liver function tests, imaging studies

Polycystic ovary syndrome

Physical exam, review of systems

Obstructive sleep apnea Physical exam, review of systems

Osteoarthritis Physical exam, review of systems

Urinary stress incontinence


Gastroesophageal reflux disease


Disability/immobility Physical exam, review of systems

Psychological disorder and/or stigmatization


Obesity secondary to genetic syndromes, hormonal disease, iatrogenic medications

Physical exam, review of systems, review of medications and supplements, family history

* Initial evaluation in patients with overweight/obesity includes: history, physical examination, review of systems, blood pressure, waist circumference, fasting glucose, fasting lipid panel (total cholesterol, LDL, HDL, triglycerides), creatinine and hepatic transaminases.

Cardiovascular and pulmonary diseases. Patients with asthma, heart failure, chronic obstructive pulmonary disease or angina can become tired or short of breath after a few min-utes of activity. Also, exercise can trigger symp-toms for patients with certain types of asthma.

Irritable bowel syndrome (IBS). Fear of diarrhea can discourage patients with IBS from enjoying walks or other outdoor exercise, Dr. Greenway notes. In addition, bloating, flatu-lence and other abdominal symptoms can prompt patients to avoid certain foods, such as high-fiber cereals and beans, making healthy eating more difficult.

Depression is common in patients with over-weight and obesity.1,6 “A person who is feel-ing depressed will have trouble finding the motivation to do all the hard work involved with losing weight and keeping it off,” says Ethan Lazarus, MD, director of the Clinical Nutrition Center in Denver and vice president of the Obesity Medicine Association. Indeed, symptoms such as fatigue, low energy, poor sleep and overeating often go hand in hand with depression.

Medication side effects. Certain anticon-vulsants, mood stabilizers, corticosteroids and other types of medication can cause weight gain, either by stimulating appetite, slowing metabolism or changing how the body stores glucose and other nutrients.8

Identifying medical issuesPrompt detection of weight-related comorbidi-ties is crucial, both to starting treatment of the illness and getting weight loss back on track. The following can point toward a diagnosis or suggest the need for further testing:

The workupAll patients with overweight/obesity should have an annual physical exam, says Dr. Lazarus, which is often the first step in diag-

Table 1. Assessment of weight-related complications*2

es can be associated with weight gain and/or interfere with a weight-loss program:

Type 2 diabetes. Insulin resistance alters glu-cose and lipid metabolism and promotes fat cell storage. Also, some classes of antihyperglyce-mics, such as sulfonylureas, thiazolidinediones and insulin, can cause weight gain.

Hypothyroidism. Low levels of thyroid hor-mone can slow metabolism.

Polycystic ovary syndrome (PCOS). This condition, marked by elevated androgen levels, irregular periods and/or multiple ovarian cysts, afflicts 1 in 10 women of childbearing age. A common symptom is weight gain that is not caused by excessive eating; others include acne, excessive facial hair, thinning hair and diffi-culty getting pregnant.

Obstructive sleep apnea (OSA) and other sleep issues. The breathing interruptions typical of OSA can leave patients sleep-deprived, inattentive, less able to manage their behavior and less motivated to exercise or eat properly, Dr. Greenway says. Further, sleep deprivation raises cortisol and decreas-es leptin, leading to metabolic changes that increase appetite and promote weight gain.

Chronic pain due to arthritis and other conditions makes exercise difficult. “Pain is a strong physiologic deterrent,” Dr. Greenway says. “Patients think about the pain and not the reasons for losing weight.” Plus, the result-ing immobility reduces muscle mass and aero-bic fitness, further deterring activity.



nosing a comorbidity. This should include basics such as checking vital signs, weight and height; heart, lung and abdominal exam; and a review of systems (see Table 1 on p. 9). Along with calculating BMI, key diagnostics include:• Blood tests, which can reveal problems

that are not only caused or worsened by excess weight, such as diabetes and nonal-coholic fatty liver disease, but also ones that increase the risk of weight gain, particularly hormonal imbalances such as hypothyroid-ism. Note: Be sure to test thyroid function in men, says Dr. Lazarus. “Many men liv-ing with obesity have never been properly screened,” he says, since thyroid deficiencies are more common in women.9

• Waist measurement. Suspect diabetes, predia-betes or insulin resistance if waist circumfer-ence is ≥35 inches in women or ≥40 inches in men, says Dr. Lazarus.

• Weight distribution check. Abdominal weight gain is a major risk factor for car-diovascular disease, diabetes and metabolic


syndrome.10-12 Whereas abdominal obesity is more prevalent in men, women are more prone to peripheral obesity, which is “less likely to cause metabolic disease than central fat, but it can still cause fatigue, immobil-ity, edema and functional problems,” Dr. Lazarus says.

• Neck circumference. Dr. Lazarus notes that a neck circumference exceeding 16 inches in women or 17 inches in men may signal obstructive sleep apnea.

• Medication review. Check to see if weight gain is a possible side effect of any medication the patient is taking (see Table 2). If possible, consider switching to a weight-neutral agent.

The patient interviewAsking patients about their overall well-being can also uncover clues to undiagnosed comor-bidities, notes Dr. Lazarus. Questions that may be helpful include:1. How are you feeling? Ask about energy level and mood, and consider using the Patient Health Questionnaire (PHQ), which can indi-cate depression. Start with the PHQ-2, suggests Dr. Lazurus, which asks: Over the past two weeks, how often have you been bothered by 1) little interest or pleasure in doing things, and 2) feeling down, depressed or hopeless? If the answers suggest depression, perform the extended PHQ-9 and/or refer to a psychiatrist.

In addition, listen for complaints about both-ersome but potentially serious symptoms. For example, morning headaches or a spouse’s report of loud snoring could signal OSA.

2. Are you sleeping well? How many hours does the patient sleep each night? Does sleep get interrupted? Does the patient feel tired during the day or while driving? Depression or OSA could be the cause.

3. Do you smoke or use alcohol? Because these high-risk behaviors are associated with weight gain, find out if or how often the patient engages in these behaviors, advises Dr. Greenway.

Antidiabetic agents (sulfonylureas, insulin, TZDs, other insulin secretagogues, e.g., glitinides)

Antidepressants (tricyclics, MAOIs, mirtazapine and certain SSRIs, including fluvoxamine, paroxetine, sertraline)

Antihistamines (azelastine, diphenhydramine)

Antipsychotics and phenothiazines (clozapine, fluphenazine, loxapine, olanzapine, quetiapine, risperidone)

Antiepileptic medications (valproic acid, carbamazepine, gabapentin)

Beta-blockers

Corticosteroids

Hormones (certain contraceptives, e.g., progestins)

Mood stabilizers (e.g., lithium)

Opiates

Osteoporosis treatment (e.g., raloxifene)

Table 2. Medications associated with weight gain8


REFERENCES1. Pereira-Miranda E, et al. Overweight and obesity associated

with higher depression prevalence in adults: a systematic review and meta-analysis. J Am Coll Nutr. 2017;36(3):223-233.

2. Martin-Rodriguez E, et al. Comorbidity associated with obesity in a large population: the APNA study. Obes Res Clin Pract. 2015;9:435-447.

3. Pickett-Blakely O. Obesity and irritable bowel syndrome: a comprehensive review. Gastroenterol Hepatol (NY). 2014;10(7):411-416.

4. Camilleri M, et al. Gastrointestinal complications of obesity. Gastroenterology. 2017;152(7):1656-1670.

5. Freedhoff Y, et al. Chapter 5: Medical barriers. In: Best Weight: A Practical Guide to Office-based Obesity Management; 2010.

6. Pratt LA, et al. Depression and obesity in the U.S. adult household population, 2005-2010. CDC NCHS Data Brief Number 167; October 2014. Available at CDC.gov.

7. Garvey WT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocr Pract. 2016;22(suppl 3):1-203.

8. Apovian CM, et al. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(2):342-362.

9. Garber JR, et al. Clinical Practice Guidelines For Hypothyroidism in Adults; Cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocr Pract. 2012;18(6):988-1028.

10. Lee JJ, et al. Association of changes in abdominal fat quality and quality with incident cardiovascular disease risk factors. J Am Coll Cardiol. 2016;68:1509-1521.

11. Freemantle N, et al. How strong is the association between abdominal obesity and the incidence of type 2 diabetes? Int J Clin Pract. 2008;62(9):1391-1396.

12. Despres JP, et al. Abdominal obesity and metabolic syndrome: contribution to global cardiometabolic risk. Arteroscler Thromb Vasc Biol. 2007;27: 2276-2283.


syndrome.10-12 Whereas abdominal obesity is more prevalent in men, women are more prone to peripheral obesity, which is “less likely to cause metabolic disease than central fat, but it can still cause fatigue, immobil-ity, edema and functional problems,” Dr. Lazarus says.

• Neck circumference. Dr. Lazarus notes that a neck circumference exceeding 16 inches in women or 17 inches in men may signal obstructive sleep apnea.

• Medication review. Check to see if weight gain is a possible side effect of any medication the patient is taking (see Table 2). If possible, consider switching to a weight-neutral agent.

The patient interviewAsking patients about their overall well-being can also uncover clues to undiagnosed comor-bidities, notes Dr. Lazarus. Questions that may be helpful include:1. How are you feeling? Ask about energy level and mood, and consider using the Patient Health Questionnaire (PHQ), which can indi-cate depression. Start with the PHQ-2, suggests Dr. Lazurus, which asks: Over the past two weeks, how often have you been bothered by 1) little interest or pleasure in doing things, and 2) feeling down, depressed or hopeless? If the answers suggest depression, perform the extended PHQ-9 and/or refer to a psychiatrist.

In addition, listen for complaints about both-ersome but potentially serious symptoms. For example, morning headaches or a spouse’s report of loud snoring could signal OSA.

2. Are you sleeping well? How many hours does the patient sleep each night? Does sleep get interrupted? Does the patient feel tired during the day or while driving? Depression or OSA could be the cause.

3. Do you smoke or use alcohol? Because these high-risk behaviors are associated with weight gain, find out if or how often the patient engages in these behaviors, advises Dr. Greenway.

4. Did your parents have health problems? Many serious diseases such as diabetes are hered-itary, notes Dr. Greenway, so family history may predict current or future health problems.

Tailoring the weight-loss regimenIf a comorbid illness is diagnosed in a patient with overweight or obesity, assess the sever-ity of the comorbidity and, if necessary, focus on getting that under control first, advises Dr. Lazarus. In the case of diabetes, medications can be tailored to help with weight loss as well as glucose control. Once the patient’s condition is stabilized, the following strategies can help them work toward their weight-loss goals:• Adjust their diet to support treatment. For

example, a lower-carb diet with four to five smaller daily meals that include at least 2 oz. of protein to promote satiety can work for many patients with insulin resistance, Dr. Lazarus says. And a diet rich in soluble fiber (e.g., oats, psyllium) could be helpful for IBS patients who confront frequent diarrhea, adds Dr. Greenway; also consider referring to a dieti-tian, as some foods can trigger IBS symptoms.

• Make physical activity easier. To circumvent limitations imposed by arthritis or chronic pain, Dr. Greenway suggests having patients start by walking 10 minutes a day and then increasing time and intensity as tolerated. For patients who have trouble walking, suggest swimming or water exercises. Referral to a physical therapist should also be considered.

• Start or resume weight-loss medication in patients with a BMI ≥30 kg/m2 or ≥27 kg/m2 plus at least one weight-related complication, Dr. Lazarus says.

• Evaluate the effects of weight loss on treatment. Dr. Greenway says that weight loss may necessitate dosage adjustment of medica-tions. For example, hypertension and diabetes usually improve as the patient loses weight, which may require a lowering or stopping of medication to avoid effects such as hypoten-sion and hypoglycemia.

• Follow-up early and often. Monitor patients fre-quently after starting a new weight-loss plan, advises Dr. Greenway. Also, be aware that patients lose water in the early stages of weight loss, so watch closely for decreases in blood pres-sure, electrolyte deficiency, constipation and other effects of dehydration. If weight loss is progressing and comorbidities are stabilized, Dr. Greenway suggests decreasing the frequen-cy of visits (e.g., every three months) once the patient achieves goal weight and moves into the weight maintenance phase. —Pete Kelly


DISKRELEASE

CONCENTRICHX FILE NAME: 118SAXP1018_HCP_ad_7.5x10.5 COLORS

FILE DESCRIPTION: Journal ad with 3 pages brief summary

MECH: CW 080218 DISK: CW 080918

Print Scale: NONECLIENT: NOVO NORDISK

BLEED: TRIM: SAFETY: SPREAD SIZE:

7.75"w x 10.75"h 7.5"w x 10.5"h 7"w x 10"h15"w x 10.5"h

C M Y K

Saxenda® and Victoza® are registered trademarks of Novo Nordisk A/S.Novo Nordisk is a registered trademark of Novo Nordisk A/S.© 2018 Novo Nordisk Printed in the U.S.A. US18SX00175 September 2018

Please see Brief Summary of Information about Saxenda® on the following pages.References

1. Saxenda® [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2017.2. Sumithran P, Prendergast LA, Delbridge E, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011;365(17):1597-1604.3. le Roux CW, Astrup A, Fujioka K, et al; for the SCALE Obesity and Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight

management in individuals with prediabetes: a randomised, double-blind trial [published online February 22, 2017]. Lancet. doi:10.1016/S0140-6736(17)30069-7.

Indications and UsageSaxenda® (liraglutide) injection 3 mg is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (eg, hypertension, type 2 diabetes mellitus, or dyslipidemia)

Limitations of Use• Saxenda® is not indicated for the treatment of type 2 diabetes• Saxenda® and Victoza® both contain the same active ingredient, liraglutide, and therefore should not be used together. Saxenda® should not be used in combination

with any other GLP-1 receptor agonist• Saxenda® has not been studied in patients taking insulin. Saxenda® and insulin should not be used together• The effects of Saxenda® on cardiovascular morbidity and mortality have not been established• The safety and effi cacy of Saxenda® in combination with other products for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations,

have not been established• Saxenda® has not been studied in patients with a history of pancreatitis

Important Safety InformationWARNING: RISK OF THYROID C-CELL TUMORSLiraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda®.

ContraindicationsSaxenda® is contraindicated in:• Patients with a personal or family history of MTC or MEN 2• Patients with a prior serious hypersensitivity reaction to liraglutide or to any of the product components• Pregnancy

Warnings and Precautions• Risk of Thyroid C-cell Tumors: If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules

noted on physical examination or neck imaging should also be further evaluated• Acute Pancreatitis: Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been

observed in patients treated with liraglutide. After initiation of Saxenda® observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, Saxenda® should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confi rmed, Saxenda® should not be restarted

Important Safety Information (cont’d)• Acute Gallbladder Disease: Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in

patients treated with Saxenda® than with placebo even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated

• Risk of Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy: When Saxenda® is used with an insulin secretagogue (eg, a sulfonylurea) serious hypoglycemia can occur. Consider lowering the dose of the insulin secretagogue to reduce the risk of hypoglycemia. Monitor blood glucose parameters prior to starting Saxenda® and during Saxenda® treatment in patients with type 2 diabetes mellitus

• Heart Rate Increase: Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed with routine clinical monitoring in patients treated with Saxenda® compared to placebo in clinical trials. Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should inform healthcare providers of palpitations or feelings of a racing heartbeat while at rest during Saxenda® treatment. For patients who experience a sustained increase in resting heart rate while taking Saxenda®, Saxenda® should be discontinued

• Renal Impairment: In patients treated with GLP-1 receptor agonists, including Saxenda®, there have been reports of acute renal failure and worsening of chronic renal failure, usually in association with nausea, vomiting, diarrhea, or dehydration, which may sometimes require hemodialysis. Use caution when initiating or escalating doses of Saxenda® in patients with renal impairment

• Hypersensitivity Reactions: Serious hypersensitivity reactions (eg, anaphylaxis and angioedema) have been reported during postmarketing use of liraglutide. If a hypersensitivity reaction occurs, patients should stop taking Saxenda® and promptly seek medical advice

• Suicidal Behavior and Ideation: In the Saxenda® clinical trials, 9 (0.3%) of 3,384 patients treated with Saxenda® and 2 (0.1%) of the 1,941 with placebo reported suicidal ideation; one of the patients treated with Saxenda® attempted suicide. Patients treated with Saxenda® should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Saxenda® in patients who experience suicidal thoughts or behaviors. Avoid Saxenda® in patients with a history of suicidal attempts or active suicidal ideation

Adverse Events• The most common adverse reactions, reported in ≥5% are: nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue,

dizziness, abdominal pain, and increased lipase

Drug Interactions• Oral Medications: Saxenda® causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral

medications. Monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda®

Use in Specifi c Populations• There are no data on the presence of liraglutide in human breast milk; liraglutide was present in the milk of lactating rats• Safety and effectiveness of Saxenda® have not been established in pediatric patients. Saxenda® is not recommended for use in pediatric patients• Saxenda® slows gastric emptying. Saxenda® has not been studied in patients with preexisting gastroparesis

Important Safety Information (cont’d)

When patients with obesity lose weight, one response of their bodies involves an increase in the hunger hormone, and a decrease in satiety hormones including glucagon-like peptide (GLP-1)—undermining their ability to lose weight and keep it off.2

Saxenda®, which is 97% similar to the native gut hormone GLP-1, activates receptors in the braina to increase satiety and thereby reduce food intake.1,a

Half of patients taking Saxenda® who achieved ≥5% body weight loss at 1 year maintained it at 3 years in a 3-year study (vs 25% and 10% for placebo, respectively).1,b

Give them the power to choose a way forward by adding Saxenda®.

To manage the chronic disease of obesity, willpower alone isn’t enough. Combined with a reduced-calorie meal plan and increased physical activity, Saxenda® can help patients lose weight and keep it off.1

WHEN IT COMES TO LOSING WEIGHT AND KEEPING IT OFF

WE HAVE THE NOW YOU CAN GIVE US THE

WILL. POWER.

Not actual patients. aShown in animal models.1

b A 160-week, randomized, double-blind, placebo-controlled study that evaluated the percentage of patients who achieved ≥5% weight loss at both 1 and 3 years. Adults with pre-diabetes and a BMI of ≥30 or ≥27 with at least one weight-related comorbidity were randomized to receive once-daily Saxenda® (n=1,505) or placebo (n=749), added to lifestyle intervention, including increased physical activity and a 500-kcal/day-defi cit diet. Study included: 4 weeks of dose escalation; 156 weeks at full dose; and 12-week off-drug observational period. Mean baseline body weight was 233.9 lb; mean BMI was 38.3. 817 Saxenda® patients vs 182 on placebo, and 391 patients on Saxenda® and 74 on placebo lost ≥5% at 1 and 3 years, respectively.1,3

People living with obesity want you to ask them about their weight-loss attempts.

Tell them how adding Saxenda® can help them lose weight and keep it off.

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Saxenda® (liraglutide) injectionRx OnlyBRIEF SUMMARY. Please consult package insert for full prescribing information.

WARNING: RISK OF THYROID C-CELL TUMORS: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions]. Saxenda® is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC with use of Saxenda® and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda® [see Contraindications, Warnings and Precautions].

INDICATIONS AND USAGE: Saxenda® is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obese), or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia). Limitations of Use: Saxenda® is not indicated for the treatment of type 2 diabetes mellitus. Saxenda® and Victoza® both contain the same active ingredient, liraglutide, and therefore should not be used together. Saxenda® should not be used in combination with any other GLP-1 receptor agonist. Saxenda® has not been studied in patients taking insulin. Saxenda® and insulin should not be used together [see Warnings and Precautions]. The effects of Saxenda® on cardiovascular morbidity and mortality have not been established. The safety and effectiveness of Saxenda® in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established. Saxenda® has not been studied in patients with a history of pancreatitis [see Warnings and Precautions].CONTRAINDICATIONS: Saxenda® is contraindicated in: Patients with a personal or family history of medullary thyroid carcinoma (MTC) or patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions]; Patients with a prior serious hypersensitivity reaction to liraglutide or to any of the product components [see Warnings and Precautions]; Pregnancy [see Use in Specific Populations]WARNINGS AND PRECAUTIONS: Risk of Thyroid C-cell Tumors: Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas and/or carcinomas) at clinically relevant exposures in both genders of rats and mice. Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether Saxenda® will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Cases of MTC in patients treated with liraglutide have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. Saxenda® is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of Saxenda® and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda®. Such monitoring may increase the risk of unnecessary procedures, due to low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin may indicate MTC, and patients with MTC usually have calcitonin values greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated. Acute Pancreatitis: Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide. After initiation of Saxenda®, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, Saxenda® should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, Saxenda® should not be restarted. In Saxenda® clinical trials, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291 Saxenda-treated patients and 2 (0.1%) of 1843 placebo-treated patients. In addition, there were 2 cases of acute pancreatitis in Saxenda-treated patients who prematurely withdrew from these clinical trials, occurring 74 and 124 days after the last dose. There were 2 additional cases in Saxenda-treated patients, 1 during an off-treatment follow-up period within 2 weeks of discontinuing Saxenda®, and 1 that occurred in a patient who completed treatment and was off-treatment for 106 days. It is unknown

whether patients with a history of pancreatitis are at increased risk for pancreatitis while using Saxenda®, since these patients were excluded from clinical trials. Acute Gallbladder Disease: In Saxenda® clinical trials, 2.2% of Saxenda-treated patients reported adverse events of cholelithiasis versus 0.8% of placebo-treated patients. The incidence of cholecystitis was 0.8% in Saxenda-treated patients versus 0.4% in placebo-treated patients. The majority of Saxenda-treated patients with adverse events of cholelithiasis and cholecystitis required cholecystectomy. Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in Saxenda-treated patients than in placebo-treated patients even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated. Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy: The risk for serious hypoglycemia is increased when Saxenda® is used in combination with insulin secretagogues (for example, sulfonylureas) in patients with type 2 diabetes mellitus. Therefore, patients may require a lower dose of sulfonylurea (or other concomitantly administered insulin secretagogues) in this setting [see Adverse Reactions]. Saxenda® should not be used in patients taking insulin. Saxenda® can lower blood glucose. Monitor blood glucose parameters prior to starting Saxenda® and during Saxenda® treatment in patients with type 2 diabetes. If needed, adjust co-administered anti-diabetic drugs based on glucose monitoring results and risk of hypoglycemia. Heart Rate Increase: Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed with routine clinical monitoring in Saxenda-treated patients compared to placebo in clinical trials. More patients treated with Saxenda®, compared with placebo, had changes from baseline at two consecutive visits of more than 10 bpm (34% versus 19%, respectively) and 20 bpm (5% versus 2%, respectively). At least one resting heart rate exceeding 100 bpm was recorded for 6% of Saxenda-treated patients compared with 4% of placebo-treated patients, with this occurring at two consecutive study visits for 0.9% and 0.3%, respectively. Tachycardia was reported as an adverse reaction in 0.6% of Saxenda-treated patients and in 0.1% of placebo-treated patients. In a clinical pharmacology trial that monitored heart rate continuously for 24 hours, Saxenda® treatment was associated with a heart rate that was 4 to 9 bpm higher than that observed with placebo. The clinical significance of the heart rate elevation with Saxenda® treatment is unclear, especially for patients with cardiac and cerebrovascular disease as a result of limited exposure in these patients in clinical trials. Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should inform health care providers of palpitations or feelings of a racing heartbeat while at rest during Saxenda® treatment. For patients who experience a sustained increase in resting heart rate while taking Saxenda®, Saxenda® should be discontinued. Renal Impairment: In patients treated with GLP-1 receptor agonists, including Saxenda®, there have been reports of acute renal failure and worsening of chronic renal failure, sometimes requiring hemodialysis [see Adverse Reactions]. Some of these events were reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, or diarrhea leading to volume depletion. Some of the reported events occurred in patients receiving one or more medications known to affect renal function or volume status. Altered renal function has been reversed in many of the reported cases with supportive treatment and discontinuation of potentially causative agents, including liraglutide. Use caution when initiating or escalating doses of Saxenda® in patients with renal impairment [see Use in Specific Populations]. Hypersensitivity Reactions: There have been reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in patients treated with liraglutide [see Adverse Reactions]. If a hypersensitivity reaction occurs, the patient should discontinue Saxenda® and other suspect medications and promptly seek medical advice. Angioedema has also been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of angioedema with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to angioedema with Saxenda®. Suicidal Behavior and Ideation: In Saxenda® clinical trials, 9 (0.3%) of 3384 Saxenda-treated patients and 2 (0.1%) of the 1941 placebo-treated patients reported suicidal ideation; one of these Saxenda-treated patients attempted suicide. Patients treated with Saxenda® should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Saxenda® in patients who experience suicidal thoughts or behaviors. Avoid Saxenda® in patients with a history of suicidal attempts or active suicidal ideation.ADVERSE REACTIONS: The following serious adverse reactions are described below or elsewhere in the prescribing information: Risk of Thyroid C-Cell Tumors [see Warnings and Precautions]; Acute Pancreatitis [see Warnings and Precautions]; Acute Gallbladder Disease [see Warnings and Precautions]; Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy [see Warnings and Precautions]; Heart Rate Increase [see Warnings and Precautions]; Renal Impairment [see Warnings and Precautions]; Hypersensitivity Reactions [see Warnings and Precautions]; Suicidal Behavior and Ideation [see Warnings and Precautions]. Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Saxenda® was evaluated for safety in 5 double-blind, placebo controlled trials that included 3384 overweight or obese patients treated with Saxenda® for a treatment period up to 56 weeks (3 trials), 52 weeks (1 trial), and 32 weeks (1 trial). All patients received study drug in addition to diet and exercise counseling. In these trials, patients received Saxenda® for a mean treatment

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duration of 46 weeks (median, 56 weeks). Baseline characteristics included a mean age of 47 years, 71% women, 85% white, 39% with hypertension, 15% with type 2 diabetes, 34% with dyslipidemia, 29% with a BMI greater than 40 kg/m2, and 9% with cardiovascular disease. In one of the 56-week trials, a subset of patients (with abnormal glucose measurements at randomization) were enrolled for a placebo-controlled 160-week period instead, followed by a 12-week off-treatment follow-up. For those participating in this 160-week period, patients received Saxenda® for a mean treatment duration of 110 weeks (median, 159 weeks). For all trials, dosing was initiated and increased weekly to reach the 3 mg dose. In clinical trials, 9.8% of patients treated with Saxenda® and 4.3% of patients treated with placebo prematurely discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were nausea (2.9% versus 0.2% for Saxenda® and placebo, respectively), vomiting (1.7% versus less than 0.1%), and diarrhea (1.4% versus 0%). Adverse reactions reported in greater than or equal to 2% of Saxenda-treated patients and more frequently than in placebo-treated patients are shown in Table 3.Table 3. Adverse Reactions Reported in Greater Than or Equal to 2% of Saxenda-treated Patients and More Frequently than with Placebo*

Placebo N = 1941

%

Saxenda N = 3384

%Gastrointestinal Disorders

Nausea 13.8 39.3Diarrhea 9.9 20.9Constipation 8.5 19.4Vomiting 3.9 15.7Dyspepsia 2.7 9.6Abdominal Pain 3.1 5.4Upper Abdominal Pain 2.7 5.1Gastroesophageal Reflux Disease 1.7 4.7Abdominal Distension 3.0 4.5Eructation 0.2 4.5Flatulence 2.5 4.0Dry Mouth 1.0 2.3

Metabolism and Nutrition DisordersHypoglycemia in T2DM1 12.7 23.0Decreased Appetite 2.3 10.0

Nervous System DisordersHeadache 12.6 13.6Dizziness 5.0 6.9

General Disorders and Administration Site ConditionsFatigue 4.6 7.5Injection Site Erythema 0.2 2.5Injection Site Reaction 0.6 2.5Asthenia 0.8 2.1

Infections and InfestationsGastroenteritis 3.2 4.7Urinary Tract Infection 3.1 4.3Viral Gastroenteritis 1.6 2.8

InvestigationsIncreased Lipase 2.2 5.3

Psychiatric DisordersInsomnia 1.7 2.4Anxiety 1.6 2.0

1 Documented symptomatic (defined as documented symptoms of hypoglycemia in combination with a plasma glucose less than or equal to 70 mg/dL) in patients with type 2 diabetes (Study 2). See text below for further information regarding hypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus

* Adverse reactions for trials with treatment period up to 56 weeks Hypoglycemia: Saxenda® can lower blood glucose. In a clinical trial involving patients with type 2 diabetes mellitus and overweight or obesity, severe hypoglycemia (defined as requiring the assistance of another person) occurred in 3 (0.7%) of 422 Saxenda-treated patients and in none of the 212 placebo-treated patients. Each of these 3 Saxenda-treated patients was also taking a sulfonylurea. In the same trial, among patients taking a sulfonylurea, documented symptomatic hypoglycemia (defined as documented symptoms of hypoglycemia in combination with a plasma glucose less than or equal to 70 mg/dL) occurred in 48 (43.6%) of 110 Saxenda-treated patients and 15 (27.3%) of 55 placebo-treated patients. The doses of sulfonylureas were reduced by 50% at the beginning of the trial per protocol. The frequency of hypoglycemia may be higher if the dose of sulfonylurea is not reduced. Among patients not taking a sulfonylurea, documented symptomatic hypoglycemia

occurred in 49 (15.7%) of 312 Saxenda-treated patients and 12 (7.6%) of 157 placebo-treated patients. In Saxenda® clinical trials involving patients without type 2 diabetes mellitus, there was no systematic capturing or reporting of hypoglycemia, as patients were not provided with blood glucose meters or hypoglycemia diaries. Spontaneously reported symptomatic episodes of unconfirmed hypoglycemia were reported by 46 (1.6%) of 2962 Saxenda-treated patients and 19 (1.1%) of 1729 placebo-treated patients. Fasting plasma glucose values obtained at routine clinic visits less than or equal to 70 mg/dL, irrespective of hypoglycemic symptoms, were reported as “hypoglycemia” in 92 (3.1%) Saxenda-treated patients and 13 (0.8%) placebo-treated patients. Gastrointestinal Adverse Reactions: In the clinical trials, approximately 68% of Saxenda-treated patients and 39% of placebo-treated patients reported gastrointestinal disorders; the most frequently reported was nausea (39% and 14% of patients treated with Saxenda® and placebo, respectively). The percentage of patients reporting nausea declined as treatment continued. Other common adverse reactions that occurred at a higher incidence among Saxenda-treated patients included diarrhea, constipation, vomiting, dyspepsia, abdominal pain, dry mouth, gastritis, gastroesophageal reflux disease, flatulence, eructation and abdominal distension. Most episodes of gastrointestinal events were mild or moderate and did not lead to discontinuation of therapy (6.2% with Saxenda® versus 0.8% with placebo discontinued treatment as a result of gastrointestinal adverse reactions). There have been reports of gastrointestinal adverse reactions, such as nausea, vomiting, and diarrhea, associated with volume depletion and renal impairment [see Warnings and Precautions]. Asthenia, Fatigue, Malaise, Dysgeusia and Dizziness: Events of asthenia, fatigue, malaise, dysgeusia and dizziness were mainly reported within the first 12 weeks of treatment with Saxenda® and were often co-reported with gastrointestinal events such as nausea, vomiting, and diarrhea. Immunogenicity: Patients treated with Saxenda® may develop anti-liraglutide antibodies. Anti-liraglutide antibodies were detected in 42 (2.8%) of 1505 Saxenda-treated patients with a post-baseline assessment. Antibodies that had a neutralizing effect on liraglutide in an in vitro assay occurred in 18 (1.2%) of 1505 Saxenda-treated patients. Presence of antibodies may be associated with a higher incidence of injection site reactions and reports of low blood glucose. In clinical trials, these events were usually classified as mild and resolved while patients continued on treatment. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to Saxenda® cannot be directly compared with the incidence of antibodies of other products. Allergic Reactions: Urticaria was reported in 0.7% of Saxenda-treated patients and 0.5% of placebo-treated patients. Anaphylactic reactions, asthma, bronchial hyperreactivity, bronchospasm, oropharyngeal swelling, facial swelling, angioedema, pharyngeal edema, type IV hypersensitivity reactions have been reported in patients treated with liraglutide in clinical trials. Cases of anaphylactic reactions with additional symptoms such as hypotension, palpitations, dyspnea, and edema have been reported with marketed use of liraglutide. Anaphylactic reactions may potentially be life-threatening. Injection Site Reactions: Injection site reactions were reported in approximately 13.9% of Saxenda-treated patients and 10.5% of placebo-treated patients. The most common reactions, each reported by 1% to 2.5% of Saxenda-treated patients and more commonly than by placebo-treated patients, included erythema, pruritus, and rash at the injection site. 0.6% of Saxenda-treated patients and 0.5% of placebo-treated patients discontinued treatment due to injection site reactions. Breast Cancer: In Saxenda® clinical trials, breast cancer confirmed by adjudication was reported in 17 (0.7%) of 2379 Saxenda-treated women compared with 3 (0.2%) of 1300 placebo-treated women, including invasive cancer (13 Saxenda- and 2 placebo-treated women) and ductal carcinoma in situ (4 Saxenda- and 1 placebo-treated woman). The majority of cancers were estrogen- and progesterone-receptor positive. There were too few cases to determine whether these cases were related to Saxenda®. In addition, there are insufficient data to determine whether Saxenda® has an effect on pre-existing breast neoplasia. Papillary Thyroid Cancer: In Saxenda® clinical trials, papillary thyroid carcinoma confirmed by adjudication was reported in 8 (0.2%) of 3291 Saxenda-treated patients compared with no cases among 1843 placebo-treated patients. Four of these papillary thyroid carcinomas were less than 1 cm in greatest diameter and 4 were diagnosed in surgical pathology specimens after thyroidectomy prompted by findings identified prior to treatment. Colorectal Neoplasms: In Saxenda® clinical trials, benign colorectal neoplasms (mostly colon adenomas) confirmed by adjudication were reported in 20 (0.6%) of 3291 Saxenda-treated patients compared with 7 (0.4%) of 1843 placebo-treated patients. Six positively adjudicated cases of malignant colorectal neoplasms were reported in 5 Saxenda-treated patients (0.2%, mostly adenocarcinomas) and 1 in a placebo-treated patient (0.1%, neuroendocrine tumor of the rectum). Cardiac Conduction Disorders: In Saxenda® clinical trials, 11 (0.3%) of 3384 Saxenda-treated patients compared with none of the 1941 placebo-treated patients had a cardiac conduction disorder, reported as first degree atrioventricular block, right bundle branch block, or left bundle branch block. Hypotension: Adverse reactions related to hypotension (that is, reports of hypotension, orthostatic hypotension, circulatory collapse, and decreased blood pressure) were reported more frequently with Saxenda® (1.1%) compared with placebo (0.5%) in Saxenda® clinical trials. Systolic blood pressure decreases to less than 80 mmHg were observed in 4 (0.1%) Saxenda-treated patients compared with no placebo-treated patients. One of the Saxenda-treated patients had hypotension

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associated with gastrointestinal adverse reactions and renal failure [see Warnings and Precautions]. Laboratory Abnormalities: Liver Enzymes: Increases in alanine aminotransferase (ALT) greater than or equal to 10 times the upper limit of normal were observed in 5 (0.15%) Saxenda-treated patients (two of whom had ALT greater than 20 and 40 times the upper limit of normal) compared with 1 (0.05%) placebo-treated patient during the Saxenda® clinical trials. Because clinical evaluation to exclude alternative causes of ALT and aspartate aminotransferase (AST) increases was not done in most cases, the relationship to Saxenda® is uncertain. Some increases in ALT and AST were associated with other confounding factors (such as gallstones). Serum Calcitonin: Calcitonin, a biological marker of MTC, was measured throughout the clinical development program [see Warnings and Precautions]. More patients treated with Saxenda® in the clinical trials were observed to have high calcitonin values during treatment, compared with placebo. The proportion of patients with calcitonin greater than or equal to 2 times the upper limit of normal at the end of the trial was 1.2% in Saxenda-treated patients and 0.6% in placebo-treated patients. Calcitonin values greater than 20 ng/L at the end of the trial occurred in 0.5% of Saxenda-treated patients and 0.2% of placebo-treated patients; among patients with pre-treatment serum calcitonin less than 20 ng/L, none had calcitonin elevations to greater than 50 ng/L at the end of the trial. Serum Lipase and Amylase: Serum lipase and amylase were routinely measured in the Saxenda® clinical trials. Among Saxenda-treated patients, 2.1% had a lipase value at anytime during treatment of greater than or equal to 3 times the upper limit of normal compared with 1.0% of placebo-treated patients. 0.1% of Saxenda-treated patients had an amylase value at anytime in the trial of greater than or equal to 3 times the upper limit of normal versus 0.1% of placebo-treated patients. The clinical significance of elevations in lipase or amylase with Saxenda® is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions]. Post-Marketing Experience: The following adverse reactions have been reported during post-approval use of liraglutide, the active ingredient of Saxenda®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Neoplasms: Medullary thyroid carcinoma [see Warnings and Precautions]; Gastrointestinal Disorders: Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death [see Warnings and Precautions]; Metabolism and Nutrition Disorders: Dehydration resulting from nausea, vomiting and diarrhea [see Adverse Reactions]; Renal and Urinary Disorders: Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis [see Warnings and Precautions]; General Disorders and Administration Site Conditions: Allergic reactions: rash and pruritus [see Adverse Reactions]; Immune System Disorders: Angioedema and anaphylactic reactions [see Warnings and Precautions]; Hepatobiliary Disorders: Elevations of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis [see Adverse Reactions]DRUG INTERACTIONS: Oral Medications: Saxenda® causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda®.USE IN SPECIFIC POPULATIONS: Pregnancy: Risk Summary: Saxenda® is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm [see Clinical Considerations]. There are no available data with liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage. Saxenda® should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Saxenda® should be discontinued. Animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 3 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD [see Animal Data]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations: Disease-associated maternal and/or embryofetal risk: A minimum weight gain, and no weight loss, is recommended for all pregnant women, including those who are already overweight or obese, due to the necessary weight gain that occurs in maternal tissues during pregnancy. Animal Data: Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison. Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison. Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities

and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day. Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group. In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times exposure in obese humans at the MRHD of 3 mg/day, based on plasma AUC comparison. A slight delay in parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. Group mean body weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutide-treated rats compared to F2 generation rats descended from controls, but differences did not reach statistical significance for any group. Lactation: Risk Summary: There are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats (see Data ). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Saxenda® and any potential adverse effects on the breastfed infant from Saxenda® or from the underlying maternal condition. Data: In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations. Pediatric Use: Safety and effectiveness of Saxenda® have not been established in pediatric patients. Saxenda® is not recommended for use in pediatric patients. Geriatric Use: In the Saxenda® clinical trials, 232 (6.9%) of the Saxenda-treated patients were 65 years of age and over, and 17 (0.5%) of the Saxenda-treated patients were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal Impairment: There is limited experience with Saxenda® in patients with mild, moderate, and severe renal impairment, including end-stage renal disease. However, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure with liraglutide, which may sometimes require hemodialysis [see Warnings and Precautions and Adverse Reactions]. Saxenda® should be used with caution in this patient population. Hepatic Impairment: There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, Saxenda® should be used with caution in this patient population. Gastroparesis: Saxenda® slows gastric emptying. Saxenda® has not been studied in patients with pre-existing gastroparesis.OVERDOSAGE: Overdoses have been reported in clinical trials and post-marketing use of liraglutide. Effects have included severe nausea and severe vomiting. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.More detailed information is available upon request.

Date of Issue: April, 2017 Version: 4Saxenda® and Victoza® are registered trademarks of Novo Nordisk A/S.PATENT Information: http://novonordisk-us.com/patients/products/product-patents.htmlManufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, DenmarkFor information about Saxenda® contact: Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536 1-844-363-4448© 2014-2018 Novo Nordisk USA18SAM01105 4/2018

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them maximize their chances of sustainably eating better, moving more and leading healthier lives,” says Scott Kahan, MD, Director of the National Center for Weight & Wellness at Johns Hopkins University and Chair of the Clinical Committee for The Obesity Society. “This includes working with them to address their environments, such as setting up their homes and workplaces to make healthier options easi-er.” Research shows it’s worth the effort: Patients with obesity who received a behavioral intervention designed to reduce exposure to obesogenic cues in their environment had significantly greater weight loss and increased physical activity—and were more likely to maintain their weight loss—compared with patients who did not receive behavioral support.3,4

The following strategies can help you empower patients to change their environments to support weight-loss therapy.

Take a team-based approach“Helping patients change their habits takes time, which healthcare providers often lack,” notes Brehm. “Lifestyle coaches are often helpful for patients,” she says, as are dietitians and physical therapists, whose services are often covered by insurance for certain comorbidities.

In addition, encourage patients to build their own support network, including at the office. “Workplace food environments are often unhealthy, which makes getting through the day eating well a challenge for many,” notes Dr. Kahan. To avoid temptation during the workday, he suggests that patients enlist the help of coworkers. “Make a pact to minimize junk foods,” Dr. Kahan says. “Plan for each participant to stock the office with healthier snack options to have on hand, rather than needing to default to the vending machines.”

P erhaps the least addressed factor contribut-ing to the obesity epidemic is the world we live in. Modern industrial and technological

changes have fostered an obesogenic environment that encourages people to eat more, move less and unconsciously adopt unhealthy habits. “Preventing weight gain and losing weight in an obesogenic environment can be like swimming upstream,” says Barbara Brehm, professor of exercise and sport stud-ies at Smith College in Northampton, MA. “Nature has given us a taste for foods that are sweet, fatty and salty, so the companies that design food products cater to those tastes.”

Numerous studies link environmental factors to weight gain. For example, a powerful prime for automatic eating is advertising, which has been shown to influence more than just brand preference: A study in Health Psychology found that adults con-sumed more unhealthy snacks after being exposed to advertising that promoted snacking and/or fun foods compared with ads that promoted better nutrition or non-food products.1

Even our near-constant exposure to digital screens could impact weight in surprising ways: When researchers at Northwestern University in Chicago simulated the blue light that’s emitted by electronic devices and LED/fluorescent lights, they discovered that a single three-hour expo-sure in the evening increased hunger levels for several hours—and also decreased sleepiness and increased insulin resistance, possibly due to altera-tions in circadian rhythm.2

The good news: Patients can increase their odds of weight-loss success by altering their environment to avoid factors that promote overeating and seden-tary behavior while making changes that encourage better choices. “We have to support patients to help

Helping patients combat an obesogenic

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❖ PAT I E N T E N G A G E M E N T

associated with gastrointestinal adverse reactions and renal failure [see Warnings and Precautions]. Laboratory Abnormalities: Liver Enzymes: Increases in alanine aminotransferase (ALT) greater than or equal to 10 times the upper limit of normal were observed in 5 (0.15%) Saxenda-treated patients (two of whom had ALT greater than 20 and 40 times the upper limit of normal) compared with 1 (0.05%) placebo-treated patient during the Saxenda® clinical trials. Because clinical evaluation to exclude alternative causes of ALT and aspartate aminotransferase (AST) increases was not done in most cases, the relationship to Saxenda® is uncertain. Some increases in ALT and AST were associated with other confounding factors (such as gallstones). Serum Calcitonin: Calcitonin, a biological marker of MTC, was measured throughout the clinical development program [see Warnings and Precautions]. More patients treated with Saxenda® in the clinical trials were observed to have high calcitonin values during treatment, compared with placebo. The proportion of patients with calcitonin greater than or equal to 2 times the upper limit of normal at the end of the trial was 1.2% in Saxenda-treated patients and 0.6% in placebo-treated patients. Calcitonin values greater than 20 ng/L at the end of the trial occurred in 0.5% of Saxenda-treated patients and 0.2% of placebo-treated patients; among patients with pre-treatment serum calcitonin less than 20 ng/L, none had calcitonin elevations to greater than 50 ng/L at the end of the trial. Serum Lipase and Amylase: Serum lipase and amylase were routinely measured in the Saxenda® clinical trials. Among Saxenda-treated patients, 2.1% had a lipase value at anytime during treatment of greater than or equal to 3 times the upper limit of normal compared with 1.0% of placebo-treated patients. 0.1% of Saxenda-treated patients had an amylase value at anytime in the trial of greater than or equal to 3 times the upper limit of normal versus 0.1% of placebo-treated patients. The clinical significance of elevations in lipase or amylase with Saxenda® is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions]. Post-Marketing Experience: The following adverse reactions have been reported during post-approval use of liraglutide, the active ingredient of Saxenda®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Neoplasms: Medullary thyroid carcinoma [see Warnings and Precautions]; Gastrointestinal Disorders: Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death [see Warnings and Precautions]; Metabolism and Nutrition Disorders: Dehydration resulting from nausea, vomiting and diarrhea [see Adverse Reactions]; Renal and Urinary Disorders: Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis [see Warnings and Precautions]; General Disorders and Administration Site Conditions: Allergic reactions: rash and pruritus [see Adverse Reactions]; Immune System Disorders: Angioedema and anaphylactic reactions [see Warnings and Precautions]; Hepatobiliary Disorders: Elevations of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis [see Adverse Reactions]DRUG INTERACTIONS: Oral Medications: Saxenda® causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda®.USE IN SPECIFIC POPULATIONS: Pregnancy: Risk Summary: Saxenda® is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm [see Clinical Considerations]. There are no available data with liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage. Saxenda® should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Saxenda® should be discontinued. Animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 3 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD [see Animal Data]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations: Disease-associated maternal and/or embryofetal risk: A minimum weight gain, and no weight loss, is recommended for all pregnant women, including those who are already overweight or obese, due to the necessary weight gain that occurs in maternal tissues during pregnancy. Animal Data: Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison. Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison. Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities

and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day. Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group. In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times exposure in obese humans at the MRHD of 3 mg/day, based on plasma AUC comparison. A slight delay in parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. Group mean body weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutide-treated rats compared to F2 generation rats descended from controls, but differences did not reach statistical significance for any group. Lactation: Risk Summary: There are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats (see Data ). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Saxenda® and any potential adverse effects on the breastfed infant from Saxenda® or from the underlying maternal condition. Data: In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations. Pediatric Use: Safety and effectiveness of Saxenda® have not been established in pediatric patients. Saxenda® is not recommended for use in pediatric patients. Geriatric Use: In the Saxenda® clinical trials, 232 (6.9%) of the Saxenda-treated patients were 65 years of age and over, and 17 (0.5%) of the Saxenda-treated patients were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal Impairment: There is limited experience with Saxenda® in patients with mild, moderate, and severe renal impairment, including end-stage renal disease. However, there have been postmarketing reports of acute renal failure and worsening of chronic renal failure with liraglutide, which may sometimes require hemodialysis [see Warnings and Precautions and Adverse Reactions]. Saxenda® should be used with caution in this patient population. Hepatic Impairment: There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, Saxenda® should be used with caution in this patient population. Gastroparesis: Saxenda® slows gastric emptying. Saxenda® has not been studied in patients with pre-existing gastroparesis.OVERDOSAGE: Overdoses have been reported in clinical trials and post-marketing use of liraglutide. Effects have included severe nausea and severe vomiting. In the event of overdosage, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms.More detailed information is available upon request.

Date of Issue: April, 2017 Version: 4Saxenda® and Victoza® are registered trademarks of Novo Nordisk A/S.PATENT Information: http://novonordisk-us.com/patients/products/product-patents.htmlManufactured by: Novo Nordisk A/S, DK-2880 Bagsvaerd, DenmarkFor information about Saxenda® contact: Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536 1-844-363-4448© 2014-2018 Novo Nordisk USA18SAM01105 4/2018

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Make portion control easierStart by asking patients to briefly track their daily habits, suggests Brehm. “Many clients benefit from writing down what they eat for a few days. We then assess their eating habits and decide on a few changes.” The key, she says, is to structure goals so they require the least amount of effort to become habits. For example, if a patient drinks four sugar-sweetened bever-ages a day, cutting them out altogether means rethinking their daily drink choices—and self-control tends to decline later in the day, Brehm notes. Therefore, suggest that patients replace two sugary drinks with noncaloric beverages such as flavored seltzer, and let them choose when to do it (for example, it may be easier to make the switch at lunch than dinner).

In addition, Dr. Kahan advises creating bar-riers to overeating, particularly with snacks. “It’s easy to take a bag of snack food, sit in front of the TV and eat mindlessly,” he notes. “When you do that, the most likely stopping point is when you’ve eaten the whole bag. Instead, take a portion, put it on a plate and then eat. If you want more, you have to go get it.” By creating these and other stopping points—say, dishing out single servings at the stove versus putting large food bowls on the table—a patient can still enjoy favorite foods in moderation while avoiding cues to overeat.

And when patients can’t control the serving size, says Dr. Kahan, planning ahead is vital. For example, restaurants tend to offer oversized portions, so he tells patients to do this: “Ask the

waiter to only serve a half portion, rather than a whole portion. Or ask for a box and put part of your serving into it before you even start eating. That way, you won’t be tempted to keep eating when you otherwise might be full.”

Guard against visual temptationSince snacks and treats like bagels and leftover cake are often readily available at the office, Dr. Kahan advises patients to stay away from the kitchen, vending machine and areas of possible temptation—such as the coworker who keeps a bowl of chocolates on his desk—to minimize exposure to unhealthy snacks. “For example, rather than walking past the kitchen to get to the bathroom, take the long way around so that you avoid the cue to grab foods that are off your plan.”

The same idea applies when patients eat out. Some type of processed starch—white-flour rolls, salty tortilla chips, crispy Chinese noodle strips—is often complimentary at restaurants, notes Dr. Kahan, and it takes willpower and decision-making energy to say no. In turn, he says, that depletes some of the mental energy needed to make healthier choices later in the meal. Therefore, patients should tell the waiter not to put the bread basket or similar item on the table, or at the very least, put it at the other end of the table and cover it with a napkin.

Store food to cue healthy choices“The way we set up our kitchens and homes can have a real impact on our behaviors,”

18 HEALTH MONITOR MEDICAL UPDATE18 HEALTH MONITOR MEDICAL UPDATE

“There are hundreds of opportunities every day—at work, at home, at restaurants—where healthier options can be set as the default.” —Scott Kahan, MD


asserts Dr. Kahan. “When healthier behaviors are easier and more automatic, we tend to do those more often.” Dr. Kahan offers this example: “If food is stored in front at eye level, you will notice it and eat it. If it’s in the back of the cupboard on the top shelf, you know it’s there but there are far fewer cues to eat it,” he says. Therefore, patients should store high-calorie items out of sight, and put healthier items like fruits and vegetables in plain sight, “so every time they open the fridge, it’s right there. These simple rearrangements do make a difference,” notes Dr. Kahan. “I tell patients to wash, peel and cut fruits and vegetables as soon as they buy them, and put the items in a nice, attractive bowl front and center. When they come home tired and hungry, the first thing they see is healthy food and there are virtually no barriers to eating it.”

Focus on increasingactivity vs. exercising “When I think of exercise, I have a frown on my face. I think of sweating, hard work, not a lot of fun,” Dr. Kahan says. “But if you think of playing a sport or being active, that has more positive connotations. Think of more fun things to do, and it is more likely you will go out and do them.” Brehm agrees and often brainstorms with clients to uncover their activ-ity preferences, such as being outside, working out with a partner or learning something new, such as yoga or tai chi.

Dr. Kahan also advises patients to find more ways to incorporate movement into their day. In fact, non-exercise activities, such as fidgeting or standing up frequently, are considered helpful for burning more daily calories. However, patients with obesity may unconsciously avoid extra movement: A small study at the Mayo Clinic reported that compared with normal-weight peers, people with obesity sat, on average, 150 minutes more each day—and subsequently burned 350 fewer calories a day.5 This isn’t necessarily a lack of motivation, noted the authors, but rather a lack of biological drive to move, and “most likely reflects a brain chemical differ-

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ence because our study shows that even when obese people lose weight, they remain seated the same number of minutes per day.”

To counteract this tendency, Dr. Kahan tells patients to look for ways to take extra steps at work—for example, by sending files to a printer that’s farther away. “Getting up a few times daily or a few times per hour and walking the extra steps to pick up what you printed can make a difference,” Dr. Kahan says. “That may seem meaningless, but it really isn’t.” In fact, studies show that moving for just a couple of minutes every hour leads to improvements in stress hormones, blood pressure and other parameters.6,7

Adds Dr. Kahan: “Many of these suggestions may seem too simple, even silly,” he acknowl-edges. “And it’s unlikely that any will, by itself, make a huge dent in weight for most people. But there are hundreds of opportunities every day—at work, at home, at restaurants, at meetings—where healthier options can be set as the default. Taken together, many of these can add up significantly.” —David Levine

❖ PAT I E N T E N G A G E M E N T

REFERENCES1. Harris JL, et al. Priming effects of television food advertising on

eating behavior. Health Psychol. 2009;28(4):404-413.

2. Cheung IN, et al. Morning and evening blue-enriched light exposure alters metabolic function in normal weight adults. PLoS ONE. 2016;11(5):e0155601.

3. Carels RA, et al. Taking control of your personal eating and exercise environment: a weight maintenance program. Eat Behav. 2008;9(2):228-237.

4. Carels RA, et al. Using motivational interviewing as a supplement to obesity treatment: a stepped-care approach. Health Psychol. 2007;26(3):369-374.

5. Levine JA, et al. Interindividual variation in posture allocation: possible role in human obesity. Science. 2005;307(5709):584-586.

6. Henson J, et al. Breaking up prolonged sitting with standing or walking attenuates the postprandial metabolic response in postmenopausal women: a randomized acute study. Diabetes Care. 2016;39:130-138.

7. Dempsey PC, et al. Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes. J Hypertens. 2016;34(12):2376-2382.


❖ CASE STUDIES

“She stopped her medication—and gained back all the weight”

“An increase in hunger had derailed weight maintenance”

History: Margaret had struggled with obe-sity for most of her life, and the consequences had severely impacted her health. Her medical history included a heart attack, high blood pressure, obstructive sleep apnea, recurrent kidney stones, depression and knee arthritis, which required her to use a cane to walk. About 13 years ago, at her highest weight of 354 lbs. with a BMI of 61, Margaret decided to have an open gastric bypass surgery. She did well after the procedure without any complications, and she eventually lost 140 lbs., which she maintained for eight years while following the prescribed diet with regular exercise. However, Margaret’s efforts at weight maintenance were hindered by progressing knee pain, which caused her to reduce her daily activity, and she started noticing some weight regain about five years ago. Then about three years ago, she noticed an increase in her appetite and, despite trying to make healthy food choices, she ended up regaining 60 lbs. rapidly. Her surgeon performed an upper GI endoscopy, which showed an anatomic breakdown in the bypass—essentially, her stomach and intestines had reconnected. Her surgeon recommended another procedure to correct it but Margaret was very scared of surgery and was referred to our medical weight-loss clinic for evaluation.

Initiating treatment: I recommended that Margaret start a weight-loss medication to help control her appetite. I reviewed her medi-cal history and saw that several of the avail-able agents were contraindicated due to her heart disease and kidney stones, as well as the antidepressant she was taking. I started her on metformin, which she tolerated well without any GI side effects. Margaret reported some

reduction in her appetite and lost about 14 lbs. before her weight stabilized. I then added on an injectable weight-loss agent, a GLP-1 agonist, which acts like the intestinal hormone GLP-1, thereby decreasing hunger and increasing sati-ety. Margaret was initially hesitant to take an injection but was pleasantly surprised that the pen was easy to use. She titrated the dosage as directed and, for the first time since she started regaining weight, Margaret felt that her excess hunger was under control. Interestingly, she had felt that same type of reduction in hunger after her bypass surgery, possibly because the procedure has been reported to work at least partially by increasing the GLP-1 response. After 11 months, Margaret had lost 60 lbs.—all the weight she had regained—and now weighs 206 lbs., the lowest she has ever been since surgery. Her ability to walk has improved and her quality of life is significantly better.

Considerations: As bariatric surgery has become more common, we see an increasing number of these patients who have regained weight. Possible physiological reasons for this, such as anatomic reversal and medications that cause weight gain, need to be assessed before attributing it to behavioral causes. One of the indicators for a physiological cause of weight regain is a sudden increase in hunger and weight after a long period of weight stability. Use of weight-loss medication in gastric bypass patients can give results that are just as reward-ing as in patients who haven’t had surgery. In Margaret’s case, finding a medication that worked prevented her from needing repeat surgery, which demonstrates how these agents can be useful in a variety of patients, even those who have undergone bariatric procedures.

PHYSICIAN: Sriram Machineni, MD, director of the obesity treatment programat University of North Carolina, Chapel Hill

PATIENT: Margaret, 62, weighed 274 lbs. with a BMI of 51.8 when she came to our clinic for treatment.



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PHYSICIAN: Gitanjali Srivastava, MD, director of the obesity medicine fellowship program/obesity medicine education at Boston University Medical Center

PATIENT: Susan, 32, weighed 198 lbs. with a BMI of 37. She has a history of anemia and bilateral knee andfoot pain.

“She stopped her medication—and gained back all the weight”

“An increase in hunger had derailed weight maintenance”

History: At her first visit, Susan com-plained of having a very difficult time losing weight despite self-directed lifestyle changes, including structured exercise and dietary pro-grams such as Atkins, Jenny Craig and others. She said that whenever she’s gone on a diet, she would lose a few pounds then gain it right back. And no matter what Susan tried, she always felt hungry. At workup, there were no signs of an eating disorder and her diet looked nutritionally balanced. She also walked 20 to 30 minutes on a treadmill several times week. Her blood pressure was 126/79 with a pulse of 82. She had no history of hypertension, diabetes or other comorbidities except knee and foot pain.

I explained to Susan that the body’s fat tissue is not inert; it is creating “negative” chemicals and hormonal signals that affect metabolism, which makes it harder to lose weight. The body tries to defend its weight “settling point” like a thermostat regulating temperature in a house. Because her BMI was above 30 and she had not responded well to numerous attempts at lifestyle changes, she was a good candidate for weight-loss medication.

Initiating treatment: I started her on an appetite suppressant, prescribing a low dose for four weeks and titrating to the full dose as tol-erated. Susan responded very well and did not have any of the common side effects, which can include increased blood pressure, migraines, shortness of breath and sleeplessness. After nine months, Susan had lost 35 lbs. and her BMI was 29.8. In addition, Susan’s knee and foot pain had resolved.

Needless to say, Susan was thrilled. Unfortunately, she was doing so well, she

stopped coming for follow-up visits—and stopped taking her medication. When she came back to see me two years later, she had regained 41 lbs.—more than the amount of weight she had initially lost, and was now 204 lbs. Not surprisingly, her foot and knee pain had returned as well.

We restarted Susan’s weight-loss medi-cation at the same dosage. At her recent four-week follow-up visit, Susan had lost 5 lbs. and was relieved to be moving in the right direction. We agreed that she would follow up monthly, and I told her that when she reaches a plateau—as most patients eventually do—our next step is to consider combination therapy with another weight-loss medication. Susan is now committed to long-term treatment, including both pharmacotherapy and lifestyle changes.

Considerations: Most weight-loss medications are intended to be taken long term, just like hypertension medication. Unfortunately, Susan’s case is very com-mon, and some may stop their medica-tion once they have reached their goal weight. However, it’s important not to blame patients or make them feel guilty. I always tell my patients who have regained weight that it is not their fault and we just need to get them back on track. I reinforce that this is a chronic disease and they are fighting the metabolic adaptations that drive weight gain. I also emphasize that losing weight doesn’t mean they’re “cured.” They still have to put 110% effort into maintaining healthy behaviors and continue taking their weight-loss medication to help their biology work the way it is supposed to work.


Q A&POTENTIAL CANDIDATES

Q Which patients might be eligible for weight-loss medication, and

how do these agents work?

A Pharmacotherapy for obesity is indi-cated in patients who have a body

mass index (BMI) ≥30 kg/m2 or those with a BMI ≥27 kg/m2 who have at least one weight-related health problem, such as hyperten-sion, diabetes or prediabetes, dyslipidemia, osteoarthritis, etc. For patients who meet these indications, do not have drug con-traindications and who have tried to lose weight on their own unsuccessfully, pharma-cotherapy should be strongly considered. In most cases, these medications decrease appe-tite, increase satiety or decrease cravings. In this way, it can help people stick with their intended diets or meal plans when hunger or cravings—which often increase in response to reduced caloric intake—would otherwise throw them off track.

—Scott Kahan, MD, Director, National Center for Weight & Wellness,

Johns Hopkins University; and Chair, Clinical Committee,

The Obesity Society

BROACHING THE TOPIC

Q When do you discuss the possible use of weight-loss medication with

your patients?

A First, it’s important to talk about life-style therapy and stress that diet and

exercise are the cornerstone of treatment. I let them know there are guidelines for when

Exploring the role of pharmacotherapy in obesity management

to consider adding on weight-loss medica-tion—and you need to have that discussion up front. I tell patients that we’re going to do the agreed upon diet and exercise plan for three months, and if that’s not working, then we can talk about pharmacotherapy.

You also have to set realistic goals. For example, if I say, “We’ve got to get 100 pounds off you,” patients will just shut down. Instead, I tell them that studies show just a 3% weight loss can improve their blood sugar and tri-glycerides. When the patient is successful, we’ll discuss reaching a goal of 5%, then 10%, etc. This motivates them to keep going and improves adherence.

—Ruchi Mathur, MD, endocrinologist and clinical researcher at the Cedars-

Sinai Diabetes & Obesity Research Institute, Los Angeles

INITIATING TREATMENT

Q How do you decide on which agent to prescribe? What patient

counseling do you provide?

A We discuss the available options, risks and benefits of pharmacotherapy in

general. Then we review each specific agent approved for weight loss in detail and what to look for when they start a medication, which includes both anticipated beneficial effects on weight as well as potential side effects. Most side effects are mild (e.g., nau-sea) if the appropriate medication is cho-sen based on patients’ pre-existing medical issues and will resolve on their own. I find that when patients are aware of potential



side effects they are more likely to weather the storm without stopping the medication and losing out on the potential benefits.

It’s important to discuss with patients that medications work as an adjunct to healthy eating and physical activity, so we work with them to have a plan in place for these impor-tant behavioral changes, and we follow up with them to support them if they are hav-ing a hard time keeping on their path. I help them appreciate the likely range of weight loss that can be expected—5% to 15% in most cases—which may not sound like a lot but usually is more than enough to improve a number of comorbidities such as hyper-cholesterolemia, hypertension and diabetes, and also enough to improve how people feel and function, including improved quality of life, better mobility and better sleep.

—Scott Kahan, MD

MANAGING EXPECTATIONS

Q How do you address patient expectations about pharma-

cotherapy? What do you do if their weight-loss goal is not achieved?

A Clinical practice guidelines on man-agement of obesity clearly state that

no weight-loss medication will work with-

out lifestyle modification and that it should be used as an adjunct rather than by itself. Many people are seeking the “easy pill solution,” so I tell patients from the start, “Don’t try to get out of this the easy way, as there is no miracle weight-loss drug.” At the same time, I reassure them, “We now have multiple tools to help you through the process and we will be in this process together. All I expect from you is that you give your best effort and I will give my best with the tools that are available.”

Fortunately, we have several options for pharmacotherapy, but you have to individualize the medication to each patient depending on their challenges and comorbid conditions—for example, some medications may raise blood pressure, cause arrhythmia or affect mood disorders. One size doesn’t fit all. Patients can respond very differently to the same medication. Reassess them frequently and consider alternative options if they don’t meet the expected weight-loss target and/or struggle with medication tolerance.

—Ji Hyun Chun (CJ), PA-C, BC-ADM, OptumCare Medical

Group, Endocrine Division, Orange County, CA; and President, American Society of Endocrine PAs

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“In most cases, weight-loss medications decrease appetite, increase satiety or decrease cravings, which can help people stick with their meal plans.” —Scott Kahan, MD


❖ E X A M T O O L


Screening for overweight/obesity

Does the patient have a body mass index (BMI) that indicates the need for weight-loss treatment?

BMI ≥30 (obesity); in certain ethnicities, the cutoff is ≥25, e.g., South Asians

BMI ≥27 (overweight) with at least one weight-related complication, such as:• Prediabetes or

type 2 diabetes• Metabolic syndrome• Hypertension• Dyslipidemia• Cardiovascular disease• Nonalcoholic fatty

liver disease• Obstructive sleep apnea• Asthma/reactive

airway disease• Osteoarthritis• Hormonal issues

(e.g., polycystic ovary syndrome, hypogonadism)

• GERD• Urinary stress incontinence

The American Association of Clinical Endocrinologists recognizes obesity as a chronic disease and recommends annual screening of BMI and other health parameters. When a patient presents with excess weight, use the checklist below to gauge the need for medical intervention, including lifestyle therapy and, when appropriate, weight-loss medication or surgery. And keep in mind: The success of treatment should be measured not solely by number of pounds lost but also by improvements in weight-related complications and overall health.

Note: For detailed recommendations on weight management, see Garvey WT, et al. AACE/ACE Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocrine Practice. 2016;22(suppl 3):1-203.

Is waist circumference indicative of cardiometabolic disease, based on these cutoffs:

Women: ≥35 inches Men: ≥40 inches

Has the patient tried lifestyle therapy (e.g., reducing calories, exercising) but was unsuccessful?

Yes No

Does the patient understand that obesity is a chronic condition due in part to genetics as well as metabolic changes?

Yes No

Is the patient motivated to set weight-loss goals and work with you on a personalized plan?

Yes No


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