final updated prasad-reddy ipha diabetes slides › 5752152618172416 › 565316480401… · õ l í...

9/15/2018

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Navigating the Diabetes Armamentarium: New Options for

Glycemic ControlLalita Prasad-Reddy, PharmD, MS, BCPS, BCACP, CDE

Clinical Assistant Professor Chicago State University

Clinical Pharmacy Specialist – Rush University Medical Center

• Dr. Prasad declares no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings and honoraria.

Disclosures and Conflict of Interest

At the conclusion of the program, the pharmacists will be able to:

• Describe recent updates in pharmacotherapy management of diabetes as it relates to cardiovascular disease.

• Discuss advantages and disadvantages of the various medication classes used to treat type 2 diabetes.

• Describe which factors guide therapeutic decision making when adding on to, or replacing metformin in type 2 diabetes.

• Compare and contrast the appropriateness of SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists for glycemic management based on specific patient characteristics.

Pharmacist Objectives

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Questions to Consider in Guiding Treatment Management of Diabetes

What patient and drug factors direct choice of agent? What patient and drug factors direct choice of agent?

What drug(s) are most appropriate to add to metformin for BG control? What drug(s) are most appropriate to add to metformin for BG control?

Are there specific disease-related conditions that dictate patient therapy? Are there specific disease-related conditions that dictate patient therapy?

Patient Case• KP is a 49yo F with type 2 diabetes for 3 years. Denies any symptoms of polyuria,

polyphagia, polydipsia. A1C increased from 7.4% to 8.4% today. She is concerned about the weight gain with insulin

• PMH• Diabetes• Hypertension• Depression• Unstable angina• Hypothyroidism• Frequent UTI’s• CKD

• Medications• Metformin 1000mg BID,• Metoprolol tartrate 50 mg bid• Lisinopril 20 mg daily• Levothyroxine 88mcg daily • Citalopram 20mg daily • Atorvastatin 20mg daily

• Social History• (-) Alcohol/tobacco• Exercise: none• Insurance: Private PPO• Diet: 1 – 2 meals/day + snacks (not watching

carbohydrates or diet)• Lives at home with husband and 3 kids

• Physical examination/Laboratory• Ht: 5’2’’, Weight 180 lbs, BMI: 32.9• BP: 128/78 mm HG• A1C 8.4% today • Notable labs:

• Potassium: 4.5 mEq/L• Serum creatinine: 1.3 mg/dL• eGFR: 44 ml/min• Albumin: Creatinine ratio: 32

– SMBG: 130 - 200 mg/dL

• Which of the following medications would be the best option to add to KP’s medication regimen?

• Liraglutide (Victoza®)

• Pioglitazone (Actos®)

• Sitagliptin (Januvia®)

• Empaglifozin (Jardiance®)

Pre-Test Question # 1 Pre-Test Question # 2

• True/False. Based upon KP’s current condition of CKD, and current estimate of kidney functioning, she is no longer a candidate for metformin therapy.

• True

• False

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Type 2 diabetes mellitus (T2DM)

DiabetesDek 2002 by Infodek

Insulin Deficiency

↓ Glucose-Induced Insulin Secretion

Decreased TissueResponse to Insulin

Insulin Resistance

↑Hepatic Glucose Production

↓Cellular Glucose Uptake

Impaired Beta Cell Function

Post receptor Defect

Hyperglycemia

Pathogenesis of Type 2 Diabetes

Liver

Pancreas

Gut

Muscle

Hyperglycemia

AdiposeTissue

T2DM: A Multisystem Disorder

Increased gluconeogenesis

Decreased glucose uptake

Decreased insulinsecretion

Decreased glucose uptake

Brain

Increasedglucagon secretion

Graphics courtesy of Robb Malone, PharmD, CPP, CDE

Increased glucagon, decreased glucose-dependent insulin

secretion

The Egregious 11

Diabetes Care 2016;39:179–186Schwartz SS, et al. Diabetes Care 2016;39:179-86.

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T2DM Pathogenesis

• Decreased insulin secretion

• Blunted “incretin effect”

• GLP-1 levels decreased in T2DM

• Less glucose-dependent insulin release and more post-prandial glucagon release

• Increased hepatic glucose production

• Insulin resistance

• Muscle

• Adipose tissue

Diabetes Mellitus in the US: Health Impact of the Disease

DiabetesLeading cause of blindness

Leading cause of renal failure

Leading cause of non-traumatic

amputation

Seventh leading cause of death

Cardiovasculardisease 2X to 4X

Healthcare costs $245 billion

30.3 million people affected

Centers for Disease Control and Prevention. National diabetes statistics report, 2017. Atlanta, GA: National Center for Chronic Disease Prevention and .

Metformin is #1• Why metformin?

• Longstanding evidence for efficacy and safety, inexpensive, generally well tolerated

• MOA: Decreases hepatic glucose production, improves insulin sensitivity

• FDA modified renal thresholds – no longer serum creatinine, based upon GFR

• Previously Scr 1.4 mg/dL (women) and Scr 1.5 mg/dL (men)

• Risk of lactic acidosis far less than originally feared

• GI issues(N/V/D): consider long-acting formulation, dose reduction, slow titration

• Monitor vitamin B12 levels and renal functionGeneral Practice Recommendations

eGFR 45 – 60 ml/min

Continue therapy, monitor renal function q 3 – 6 months

eGFR 30 – 45 ml/min

Avoid initiation of metforminConsider dose adjustment, max 500mg BID

American Diabetes Association. Standards of Medical Care in Diabetes –2018. Diabetes Care 2018;41(suppl. 1):S1-159.

But what comes next???

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Management of Hyperglycemia in T2DM

• Metformin remains the first-line option

• Controversial on what is next!!!• Lack of comparative data on different regimens

• Concerns about benefits/risks of intensive control on macrovascular events

• Increasing complexity of therapeutic options

• Potential adverse effects

• Individualization of treatment

• Patient preferences and tolerance


American Diabetes Association (ADA) Treatment Approach

Initial Treatment

• Lifestyle interventions + Metformin are 1st line for most• If A1C≥9%, consider dual therapy (utilize CV risk to determine agent)• IF A1C≥10% or BG>300mg/dL, consider combination or injectable therapy

Not at Goal at 3

months?

• Assess medication taking behavior• Add a 2nd oral agent or long-acting insulin or a GLP-1 receptor agonist

Not at Goal at 6

months?

• Assess medication taking behavior• Add a 3rd oral agent or long-acting insulin or a GLP-1 receptor agonist

cost, potential side effects, weight, comorbidities, Use a patient-centered approach taking into account cost, potential side effects, weight, comorbidities,

hypoglycemia risk, patient preferences, cardiovascular effects


American Diabetes Association (ADA) Treatment Approach


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Metformin

Sulfonylureas

GlyburideGlipizide

Glimeperide

Thiazolidinediones

PioglitazoneRosiglitazone

SGLT-2 Inhibitors

CanagliflozinDapagliflozinEmpagliflozinErtugliflozin

DPP-4 Inhibitors

SitagliptinSaxagliptinLinagliptinAlogliptin

Insulin

Nasal

InsulinRapid, Short

IntermediateBasal

Premixed Nasal

Available Antihyperglycemic Therapies (1st or 2nd line)

GLP-1 RA ExenatideLiraglutide

LixisenatideDulaglutideSemaglutide

And many combinations…



Sulfonylureas

• Second generation: glipizide, glimepiride, glyburide

• MOA: Stimulate beta cells in the pancreas to release insulin

• Adverse effects

• Hypoglycemia

• Weight gain

• Rash

• Beta cell burnout? - Decreased longevity

• Cardiovascular risk?

• Inhibition of myocardial ischemic preconditioning

• Low cost, effective A1C lowering


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Thiazolidendiones(TZD’s)• TZD’s include pioglitazone, rosiglitazone

• MOA: Activates the nuclear transcription factor PPAR-gamma, increases peripheral insulin sensitivity

• Adverse effects

– Bone fractures

– Edema/fluid retention

– Weight gain

– Reported cases of liver failure

• Avoid in NYHA Class III or IV heart failure

• Clinical considerations

• Cardiovascular disease, Bladder Cancer


Incretin Physiology

Plasma Glucose

Tissues

GlucoseDisposal

Rate ofglucose

appearance

Rate ofglucose

disappearance

Stomach

BrainFoodIntake—

GastricEmptying

—

Liver

GLP-1

Gut

PostprandialGlucagon

Pancreas

Insulin

Illustration courtesy of Amylin PharmaceuticalsGedulin BR, et al. Endocrinology 2005; 146:2069-76.

De Leon DD, et al. The International Journal of Biochemistry & Cell Biology 2005 Sep 29Kruger DF. Drugs 2004; 64:1419-32.

DPP-4 Enzyme

Dipetidyl Peptidase-4 (DPP-4) Inhibitors

4 available agents

Sitagliptin(Januvia®)

Saxagliptin(Onglyza®)

Linagliptin(Tradjenta®)

Alogliptin(Nesiba®)

Well tolerated Most common ADR’s: headache, upper respiratory infections, urinary tract infections FDA alerts: pancreatitis, joint pain, heart failure

MOA: Inhibits DPP-4 activity, increasing postprandial incretin (GLP-1, GIP)

concentra ons: ↑ Insulin secre on, ↓ glucagon secre on (glucose dependent)


DPP-IV Agent Comparison

Sitagliptin (Januvia®) Saxagliptin (Onglyza®) Linagliptin(Tradjenta®)

Alogiptin(Nesiba®)

High selectivity for DPP-4 enzyme

Moderate selectivity for DPP-4 enzyme



DPP-4 inhibition ~97% (24 hours post-dose)

DPP-4 inhibition ~80% (24 hours post-dose)

DPP-4 inhibition > 80%

(24 hours post-dose)

DPP-4 inhibition ~ 75% (24 hours post dose)

Dose not undergo appreciable metabolism

Metabolized by CYP3A4 enzyme system

Weak – Moderate Inhibitor of CYP3A4

enzyme system

Not appreciably metabolized

Renal excretion Renal excretion Non-renal excretion Renal excretion

Deacon C.F. Diabetes, Obesity and Metabolism. 2011. 13:7-18.

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DPP-4 Inhibitors: Adverse Effects

• FDA Alert (Aug, 2015): 33 cases from 2006-2013 in FAERS• Occurred 1 day to years after initial use• After discontinuation, symptoms relieved

Joint Pain

• FDA update April 2016 for alogliptin and saxagliptin• EXAMINE: Alogliptin increased HF hospitalizations (3.9% vs 3.3%) • SAVOR-TIMI: Saxagliptin increased hospitalization rates for HF (3.5% vs. 2.8%,)

Heart Failure

• FDA alert in 2009 due to post-market reports• Higher rates in clinical trials compared to placebo• Also seen with GLP-1 receptor agonists

Pancreatitis

https://www.fda.gov/Drugs/DrugSafety/ucm459579.htmPL Detail-Document, DPP-4 Inhibitors (Gliptins) and Risk of Heart Failure. Pharmacist’s Letter/Prescriber’s Letter. June 2016.

https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm494252.htm Accessed 4/13/17

Glucagon-Like-1 Receptor Agonists (GLP-1 RA)

• MOA: Activates GLP-1 Receptors

– ↑ Insulin secretion (glucose dependent)

– ↓ Glucagon secretion (glucose dependent)

– Slows gastric emptying

– ↑ Sa ety

• Supra-therapeutic levels of GLP-1

– Higher levels achieved compared to DPP-4 inhibitors

• Common adverse effects

• Nausea/vomiting, injection site reactions, weight loss, increased heart rate

• Bydureon®: SQ nodules

• Warnings include pancreatitis, thyroid C-cell tumors, gallstonesDiabetes Care 2017;40(Suppl. 1):S64–S74.

Detail-Document, Comparison of GLP-1 Agonists. Pharmacist’s Letter/Prescriber’s Letter. December 2014Lixisenatide. Micromedex 2.0. Available at: http://www.micromedexsolutions.com. Accessed April, 2017.

AvailableGLP-1RAsGLP-1 RA Dosing (All SQ) Clinical Considerations

Exenatide (Byetta®)

5 – 10 mcg BID • Primarily affects postprandial glucose due to delays in gastric emptying• High risk of GI adverse effects, may take longer than long-acting GLP-1 agonists to become

nausea free• Dose escalation precautions required for CKD

Liraglutide(Victoza®)

0.6 – 1.8 mg daily

• More pronounced effects on fasting blood glucose• Administer at anytime of the day• Dose adjustments not recommended

Lixisenatide(Aldyxin®)

10 – 20 mcg daily

• Administer 1 hour prior to first meal of day• Although administered once daily, half life is short with most robust effect on postprandial

glucoses• Dose adjustments not recommended, but gastrointestinal disturbances and dehydration can

worsen renal concerns

Exenatide QW (Bydureon®)

2 mg once weekly

• Available as two formulations - one prefilled pen, and one that requires patient reconstitution• Steady state concentrations are not reached until week 7• Dose escalation precautions required for CKD

Dulaglutide(Trulicity®)

0.75 – 1.5 mg weekly

• Achieves therapeutic concentrations faster than other agents (3 - 7 days)• Less efficacy in reducing satiety (presumably due to less effect on CNS through limited passage

in the blood-brain barrier

Semaglutide (Ozempic®)

0.25 mg weekly • Potential concerns of progression of diabetic retinopathy with this agent• Dose adjustments not required

GLP-1 RA: Adverse Effects

Gallbladder Disease• Increased risk of bile duct and

gallbladder disease possibly due to rapid weight loss

• Higher rates seen in the SCALE and LEADER studies

• Patient counseling

– Diet modifications and warning signs of right upper quadrant pain that can radiate to the shoulder

Thyroid Disease• Thyroid C-cell tumors have occurred in

rats and mice at clinically relevant exposures

– Black Box Warning

– Higher rates with increased dose and duration

– Avoid use in multiple endocrine neoplasia syndrome type 2 or personal or family history of medullary thyroid carcinoma

Professional Resource, GLP-1 Agonists and Gallbladder Disease. Pharmacist’s Letter/Prescriber’s Letter. October 2016. Liraglutide package insert, Dulaglutide package insert.

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Sodium-Glucose Co-Transportor-2 (SGLT-2) Inhibitors

Pros• Unique MOA

• Lowers BP

• Weight loss

• Low risk of hypoglycemia

• Positive CV outcome data (Jardiance®, Canagliflozin®)

Cons

PL Detail-Document, Drugs for Type 2 Diabetes. Pharmacist’s Letter/Prescriber’s Letter. September 2016

MOA: Inhibits SGLT-2 in the proximal renal tubule; blocks glucose reabsorption by the kidney, increasing glucosuria

Canagliflozin(Invokana®)

Dapagliflozin(Farxiga®)

Empagliflozin (Jardiance®)

Ertugliflozin(Steglartro®)

• Genitourinary tract infections

• Hypovolemia

• Bone fractures

• Leg/foot amputations

• Acute kidney injury

• Euglycemic DKA

SGLT2-Inhibitors: Adverse Effects

• FDA warning added to canagliflozin in Sept 2015• A pooled analysis of 9 trials over 85 weeks compared canagliflozin to placebo: more bone fractures

with Cnagligflozin (1.5 vs. 1.1) per 100 patient-years

Bone loss

• FDA warning updated June 2016 for canagliflozin, dapagliflozin• 2013-2015, FDA received 101 confirmed cases of acute kidney injury

Acute Kidney Injury

• FDA warning added Dec 2015• 19 cases of life-threatening urosepsis and pyelonephritis with canagliflozin(n=10) and

dapagliflozin(n=9)

Urosepsis

• FDA warning added May 2015 (updated Dec 2015)• 73 cases of DKA reported in FAERS

Diabetic Ketoacidosis

Amputations

FDA Drug Safety Communication:. Available from:https://www.fda.gov/Drugs/DrugSafety/ucm461449.htm Accessed 4/13/17https://www.fda.gov/Drugs/DrugSafety/ucm505860.htm Accessed 4/13/17

FDA Drug Safety Alert. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm446845.htm. Accessed: 3/20/17

Drug Selection: A Balancing Act

Clinical Outcomes

Patient Safety

Considerations in Drug Selection

Mechanism of Action

Effects on A1C, FBG,

PPG

Cost Effects on Weight

Hepatic/Renal Thresholds

Medication Adherence

Adverse Effects

Risk of Hypoglycemia

Patient Preferences

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Impact on A1C and Glucose

•Think: how low do you need to go? Ex: More A1C lowering with GLP-1 RA vs. DPP4 inhibitor

• Insulin has the most A1C lowering potentialA1C Lowering

•Metformin, TZD’s, SGLT-2 inhibitors, long acting GLP-1 RA’s, long acting insulinFBG Coverage

PPG Coverage

•Sulfonylureas, long acting GLP-1 RA’s FBG/PPG Coverage

• DPP-4 inhibitors, short-acting GLP-1 RA’s, alpha-glucosidase inhibitors, meglitinides, rapid/short-acting insulin

A. American Diabetes Association. 9. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2018. Dibetes Care 2018;41(uppl. 1):S86-104.

Macrovascular Complications

Patients with DM have 2 – 6 times higher risk of development of CV diseaseCHD risk equivalent

Treatment may be less efficacious than general population

Poorer prognosis than individuals without clinically apparent DM Protective effect for females is lost in women

with DM

Landmark TrialsStandards of Care, 2018 Guidelines

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Objective Study Design Results

To assess the long-term effects of liraglutide on cardiovascular outcomes and other clinically important events in patients with T2DM and high risk of cardiovascular disease• Primary outcome:

composite of CV death, nonfatal MI, nonfatal stroke

Multicenter, double-blind, placebo-controlled trial at 410 sites in 32 countries

Patients randomized to 2 week placebo run in period, then randomized 1:1 to liraglutide 1.8mg or placebo once daily + standard of care

The primary composite outcome occurred in fewer patients in the liraglutide group 13.0% than in the placebo group 14.9% (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority)

Death from cardiovascular causes occurred in fewer patients in the liraglutide group (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007)

The rate of death from any cause was also lower in the liraglutidegroup than in the placebo group ( (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02)

LEADER Trial

Marso SP, et al. N Engl J Med. 2016:375:311-322.

Hazard ratio (95% CI) P value

Primary composite endpoint* 0.87 (0.78-0.97) 0.01

Expanded composite endpoint† 0.88 (0.81-0.96) 0.005

Death from any cause 0.85 (0.74-0.97) 0.02

CV death 0.78 (0.66-0.93) 0.007

Fatal or nonfatal MI 0.86 (0.73-1.00) 0.046

Nephropathy 0.78 (0.67-0.92) 0.003

Clinical Outcomes with Liraglutide

LEADER(N=9340)


0.00 0.20 0.40 0.60 0.80 1.00 1.20

Median follow-up: 3.5 years

LEADER Trial –OUTCOMES


LEADER: Selected Safety Results

Adverse Event Liraglutide (%) Placebo (%) P-Value

Any ADE 62.3 60.8 0.12

Serious ADE 49.7 50.4 0.51

Confirmedhypoglycemia

43.7 45.6 0.06

Severe hypoglycemia 2.4 3.3 0.02

Acute gallstone disease 3.1 1.9 < 0.001

Injection site reaction 0.7 0.3 0.002

ADE leading to discontinuation of trial

9.5 7.3 <0.001


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Objective Study Design

To assess the effects of empagliflozin an in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk

Multicenter, randomized, double blind, placebo controlled at 590 sties in 42 countries

The primary outcome occurred in 10.5% in the pooled empagliflozin group and in 12.1% in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P=0.04 for superiority)

Empagliflozin was associated with significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction)

EMPA-REG (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes)

Hazard ratio (95% CI) P value

Primary composite endpoint* 0.86 (0.74-0.99) 0.04

Secondary composite endpoint† 0.89 (0.78-1.01) 0.08

Death from any cause 0.68 (0.57-0.82) <0.001

CV death 0.62 (0.49-0.77) <0.001

Fatal or nonfatal MI 0.87 (0.70-1.09) 0.23

Hospitalization for HF 0.65 (0.50-0.85) 0.002

Hospitalization for HF or CV death 0.66 (0.55-0.79) <0.001

Clinical Outcomes with Empagliflozin

EMPA-REG OUTCOME Pooled Analysis(N=7020)

Zinman B, et al. N Engl J Med. 2015;373:2117-2128.

0.00 0.20 0.40 0.60 0.80 1.00 1.20

Primary Outcome Results – EMPA-REGSafety Outcomes with Empagliflozin

Zinman B, et al. N Engl J Med. 2015;373:2117-2128.

Event Pooled Empagliflozin (%) Placebo (%)

Any adverse event 90.2 91.7

Serious adverse event 38.2 42.3

Death 3.8 5.1

Any hypoglycemia 27.8 27.9

Severe hypoglycemia 1.3 1.5

Urinary tract infection Male 18.0 18.1

Genital infection 6.4 1.8

Volume depletion 5.1 4.9

Diabetic ketoacidosis 0.1 <0.1

Bone fracture 3.8 3.9

Acute kidney failure 5.2 6.6

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Objective Study Design Results

To assess the effects of empagliflozin an in addition to standard care, on cardiovascular,renal, and safety outcomes in patients with type 2 diabetes at high cardiovascular risk• Primary outcome

composite of CV death, nonfatal MI (excluding silent MI), or nonfatal stroke

Multicenter, randomized, double blind, placebo controlled at 667 sites in 30 countries

The primary outcome was significantly lower with patients treated with canagliflozin than with placebo (occuring in 26.9 vs. 31.5 participants per 1000 patient years; HR 0.86, 95% CI (0.75-0.97), p <0.001 for noninferirotiy; p = 0.02 for superiority)

Canagliflozin was associated lower progression of albuminuria,the need for renal-replacement therapy, and death from renal causes.

Canagliflozin was associated with an increased risk of amputation at the toe or metatarsal

Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

Neal B, et al. NEJM 2017;377:644-657

Hazard ratio (95% CI)

Primary composite endpoint* 0.86 (0.75-0.97)

CV death 0.87 (0.72-1.06)

Nonfatal MI 0.85 (0.69-1.05)

Nonfatal stroke 0.90 (0.71-1.15)

Fatal or nonfatal MI 0.89 (0.73-1.09)

Fatal or nonfatal stroke 0.87 (0.69-1.09)

HF hospitalization 0.67 (0.52-0.87)

CV death or HF hospitalization 0.78 (0.67-0.91)

All-cause death 0.87 (0.74-1.01)

Progression of albuminuria 0.73 (0.67-0.79)

40% reduction in eGFR, renal replacement therapy, or renal death

0.60 (0.47-0.77)

Clinical Outcomes with Canagliflozin

0.00 0.50 1.00 1.50

Neal B, et al. NEJM 2017;377:644-657

Adverse Events with Canagliflozin

Event Canagliflozin Placebo P value

Events per 1000-patient years

All serious adverse events 104.3 120.0 0.04

Adverse events leading to discontinuation 35.5 32.8 0.07

Diabetic ketoacidosis (adjudicated) 0.6 0.3 0.14

Amputation 6.3 3.4 <0.001

Bone fracture (adjudicated) 15.4 11.9

Infection of male genitalia 34.9 10.8 <0.001

Osmotic diuresis 34.5 13.3 <0.001

Volume depletion 26.0 18.5 0.009

Mycotic genital infection in women 68.8 17.5 <0.001

Urinary tract infection 40.0 37.0 0.38

Acute kidney injury 3.0 4.1 0.33

Neal B, et al. NEJM 2017;377:644-657American Diabetes Association. 9. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2018. Dibetes Care 2018;41(uppl. 1):S86-104.

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CVDCVD CKDCKD ObesityObesity

Heart FailureHeart Failure OsteoporosisOsteoporosis

Drug-Disease Considerations • KP is a 49yo F with type 2 diabetes for 3 years. Denies any symptoms of polyuria,

polyphagia, polydipsia. A1C increased from 7.4% to 8.4% today. She is concerned about the weight gain with insulin

• PMH• Diabetes• Hypertension• Depression• Unstable angina• Hypothyroidism• Frequent UTI’s• CKD

• Medications• Metformin 1000mg BID• Metoprolol tartrate 50 mg bid• Lisinopril 20 mg daily• Levothyroxine 88mcg daily • Citalopram 20mg daily • Atorvastatin 20mg daily

• Social History• (-) Alcohol/tobacco• Exercise: none• Insurance: Private PPO• Diet: 1 – 2 meals/day + snacks (not watching

carbohydrates or diet)• Lives at home with husband and 3 kids

• Physical examination/Laboratory• Ht: 5’2’’, Weight 180 lbs, BMI: 32.9• BP: 128/78 mm HG• A1C 8.4% today • Notable labs:

• Potassium: 4.5 mEq/L• Serum creatinine: 1.3 mg/dL• eGFR: 44 ml/min• Albumin: Creatinine ratio: 32

– SMBG: 130 - 200 mg/dL

Back to the Patient Case

• Which of the following medications would be the best option to add to KP’s medication regimen?

• Liraglutide (Victoza®)

• Pioglitazone (Actos®)

• Sitagliptin (Januvia®)

• Empaglifozin (Jardiance®)

Liraglutide is the only appropriate option for KP in this case. Given her history of ASCVD, liraglutide or empaglifozin are both options. However, she has a frequent history of UTI’s, so in this case, the GLP-1 agonist would provide the greatest benefit to

her A1C, as well as prevent CVD mortality.

Post-Test Question # 1 Post-Test Question # 2

• True/False. Based upon KP’s current condition of CKD, and current estimate of kidney functioning, she is no longer a candidate for metformin therapy.

• True

• False

The guidelines for metformin dosing have changed! While previously metformin was dosed based upon Serum Creatinine as an index, GFR now serves as the dosing guide for metformin. Given her degree of CKD, it would be prudent to decrease the overall dose to decrease the overall risk of lactic acidosis.

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Individualization for therapy after metformin should be based upon current disease state, degree of A1C lowering desired, and other co-morbid conditions.

For patients with history of ASCVD, SGLT-2 inhibitors, as well as GLP-1 agonists have demonstrated reduction in overall cardiovascular mortality.

Clinicians should utilize an individual approach when selecting add-on therapy to patients’ diabetes regimens.

Medications should never substitute appropriate patient counseling on self-care behaviors.

TAKE HOME POINTS References ADA Standards of Care. American Diabetes Association. Standards of Medical Care in Diabetes – 2018. Diabetes Care 2018;41(suppl. 1):S1-159.

AACE . Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Management Algorithm. Endocrine Practice. 2018;24(1): 91- 120.

Cefalu et al. Cardiovascular Outcomes Trials in Type 2 Diabetes: Where Do We Go From Here? Reflections from a Diabetes Care Editors’ Expert Forum. Diabetes Care. 2018;41(1): 14-31.

Chaudhury et al. Clinical Review of Antidiabetic Drugs: Implications for Type 2 Diabetes Mellitus Management. Front Endocrinol (Lausanne). 2017;8(6).

Lalita Prasad-Reddy, PharmD, MS, BCPS, BCACP, CDE

[email protected]

final updated prasad-reddy ipha diabetes slides › 5752152618172416 › 565316480401… · õ l í...

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