MARGARITA SIANOSYAN, DOCTOR OF PHARMACY CANDIDATE, LECOM COLLEGE OF PHARMACY

GLP-1 Analogs and Lifestyle Modifications

Overview

GLP-1 analog’s role in the body Available GLP-1 analogs on the market Advantages over other anti-diabetic agents Benefits when combined with lifestyle

modifications Importance of healthy diet, physical activity,

and sleep with GLP-1 analogs Nutrition and physical activity

recommendations

GLP-1 in Type 2 Diabetes

Ganda, Om. Diabetes and the GI Tract: Important Interrelationship. Medscape reference. WebMD 2011.

GLP-1 Analogs

Synthetic and structurally-altered version of naturally produced hormone

Mimic physiological actions of GLP-1 Naturally produced GLP-1 are rapidly

inactivated by (dipeptidyl-peptidase 4) DPP-4 enzyme

Half life is 1-2 minutes GLP-1 analogs are resistant to inactivation by

DPP-4 enzyme and stay longer in the body Work only in presence of glucose

Dungan K. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA 2012.

Mechanisms of Action

Glucose-dependent insulin production

Stimulates beta-cells and causes insulin secretion

Inhibits glucagon secretion

Delays gastric emptying Induces satiety and

decreases food intake Improves beta-cell

function and proliferation (animal studies)

Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/features/12372http://www.soc-bdr.org/e4/e887/volRdsVolumes5237/issRdsIssues5874/chpRdsChapters5886/strRdsArticles5887/index_en.html?preview=preview&showfulltext=1

Satiety and Food Intake

Long term weight loss Exact mechanism is unclear

Acts on hypothalamic feeding centers

Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/features/12372http://www.funderstanding.com/educators/brain-anatomy/

GLP-1 Analogs on the Market

Used as an adjunct to diet and exercise to improve glycemic control

Administered by subcutaneous injection Byetta (Exenatide) – twice daily SQ

injection Victoza (Liraglutide) – once daily SQ

injection Bydureon (extended-release Exenatide) –

once weekly SQ injection

Dungan K. Glucagon-like peptide-1-based therapies for the treatment of type 2 diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA 2012.

Safety Profile

Mild or moderate nausea Titrating dose may limit nausea

Diarrhea Headaches Dizziness Hypoglycemia when taken with sulfonylureas Rare cases of acute pancreatitis and renal

dysfunction Exenatide should not be used in patients with

creatinine clearance <30 mL/min

McCulloch DK, Munshi M. Treatment of type 2 diabetes mellitus in the elderly patient. In UptoDate, Nathan DM, Schmader KE (Ed), UpToDate, Waltha, MA.2012.http://www.uptodate.com/contents/treatment-of-type-2-diabetes-mellitus-in-the-elderly-patient

GLP-1 with other Anti-diabetics

Can be used alone or in combination with other anti-diabetic agents

Combination with dipeptidyl-peptidase-4 (DPP-4) inhibitors is not recommended and is not FDA approved

Hester, SA. Pharmacist’s Letter. Combining a GLP-1 Agonist and a DPP-4 Inhibitor for Type 2 Diabetes. Stockton, CA: Therapeutic Research Faculty; [online] http://www.pharmacistsletter.com. September 5, 2012.http://www.ehow.com/how_7433049_use-byetta-pen.html

In Comparison to Other Anti-diabetics

Less incidence of hypoglycemia

Greater reduction in A1C levels

Weight reduction Undesirable effects of

other anti-diabetic agents can lead to non-adherence to medications

Diabetes Obes Metab. (2012, April 9). GLP-1 a Good Choice for Glycemic Control?. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/53-diabetes-news/12658-glp-1-a-good-choice-for-glycemic-controlhttp://www.freediabetestestsupplies.com/cinnamon-diabetes-natural-cure/

Cardiovascular Health

Primary cause of death in Type 2 Diabetes patients is cardiovascular disease (CVD)

GLP-1 agonists lower blood pressure and cholesterol

Increased cardiac contractility and protection against ischemia

Spellman CW. (2010). Pharmacology of GLP-1 Agonists: Describing the Therapeutic Potential to Patients. The Journal of the American Osteopathic Association, 11(2), eS10-eS14. Retrieved September 5, 2012 from http://www.jaoa.org/content/111/2_suppl_1/eS10.full http://www.virtua.org/health/cardiovascular-health.aspx

Adjunct to Diet and Weight Control

Works best when combined with healthy diet and physical activity

Diet and weight control

Slows progression to Type 2 diabetes

Prevents complications

Conetta C, Patel, M. (2012, February 22). GLP-1 Analogs and DeFronzo's Octet. Diabetes in Control. Retrieved September 5, 2012, from http://www.diabetesincontrol.com/articles/features/12372http://www.northcentraliaredcross.org/wp-content/uploads/2012/03/Healthy-Foods_C.gif

Medical Nutrition Therapy (MNT)

“Nutritional diagnostic, therapy, and counseling services for the purpose of disease management, which are furnished by a registered dietitian or nutrition professional.”

Key component in preventing diabetes, managing diabetes, and preventing associated complications

Covered by Medicare and many other private and state insurance plans

American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18

Medical Nutrition Therapy (MNT)

Current literature supports MNT as an effective method for treating diabetes

18 studies reviewed by ADA 8 were randomized controlled

trials Intervention groups had greater

improvements in A1C levels and fasting plasma glucose

Lifestyle modifications play an important role in managing diabetes

American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://www.cvmc.org/hospital/departments-services/patient-support-services/nutrition-diabetes-counseling

Diet

Important to reinforce healthy diet

Types of foods Limiting foods high in sugar,

salt, and fat Frequency

Eating smaller portions throughout the day

Portion control Keeping track of carbohydrate

intake

American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://www.saintshealthymarriages.com/healthy-diet-plans/

Nutrition

Complex carbohydrates (55%), protein (20%), healthy fats (25%)

High fiber carbohydrate foods

Saturated fat intake of <7% of total calories

Minimal trans fat intake

American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://concordweightloss.com/2011/05/03/downsize-portions-for-better-weight-control/

Physical Activity

At least 150 minutes per week of moderate-intensity aerobic physical activity

50-70% of maximum heart rate

Resistance training three times a week

American Diabetes Association. Medical Nutrition Therapy: A Key to Diabetes Management and Prevention-2010. Clinical Diabetes. 2010;28:12-18 http://extrachapter.com/exercise-and-diabetes/

Weight Control

Even small amounts of weight loss can improve glycemic control

Changes in BMI can reduce A1C and blood pressure

Improve lipid levels Reduce cardiovascular

risk factors

American Diabetes Association. Weight Loss, Glycemic Control, and Changes in Cardiovascular Biomarkers in Patients With Type 2 Diabetes Receiving Incretin Therapies or Insulin in a Large Cohort Database-2010. Diabetes Care. 2010; 33:1759-1765. http://www.askcms.com/weight-loss/natural-weight-loss-supplements/

Sleep

In addition to healthy diet and exercise, sleep also has an important role in weight control

Study found that middle-aged, overweight men who slept 8.5 hours burned more fat than patients that slept 5.5 hours

Elevated levels of ghrelin in the blood

Ann Intern Med. 2010;153:435-441, 475-476www.adultspancounseling.com/wp-content/uploads/2008/04/ManSleeping.jpg

Conclusion

GLP-1 analogs have several mechanisms of action in the body.

GLP-1 analogs’ advantages over other anti-diabetic agents include less hypoglycemia, better A1C control, no weight gain, and cardioprotection.

GLP-1 analog therapy is used as an adjunct to healthy diet and exercise.

Healthy lifestyle modifications are necessary for successful treatment.