When Diet and Exercise Aren t Enough: Pharmacologic Management of Obesity

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2 When Diet and Exercise Aren t Enough: Pharmacologic Management of Obesity Casey Bonaquist, DO Saturday, April 30 th, th Annual Primary Care & Cardiovascular Symposium

3 Learning Objectives After participating in this lecture, healthcare providers will be able to: Select appropriate patients for anti-obesity pharmacotherapy Understand the metabolic effects of therapy Compare the profiles of anti-obesity agents Utilize shared decision making with patients

4 Obesity Recognized as a Disease Obesity is a chronic disease, and both the patient and practitioner need to understand that successful treatment requires a life-long effort. National Institutes of Health (1998)

5 Obesity as a Disease Recognized By: Food and Drug Administration American Medical Association (2013) Internal Revenue Service

6 Goals of Medical Weight Loss 5 to 10% Weight Loss - Reduces Cardiovascular Disease Risk Factors - Prevents/Delays Progression of diseases such as Type II Diabetes - Improves Obesity Related Conditions NIH

7 Guidelines for Medication Use o ADJUNCT TO OTHER THERAPIES o NUTRITIONAL, PHYSICAL ACTIVITY AND BEHAVIORAL o BMI 30 kg/m 2 o If comorbidities, BMI 27 kg/m 2 o Reassessment after 12 weeks o Not pregnant US Department of Health and Human Services (2013)

8 Anti-Obesity Pharmacotherapy Approved by the FDA Agents Action Approval Phentermine Noradrenergic Sympathomimetic 1959 Orlistat Pancreatic Lipase Inhibitor 1997 Lorcaserin Serotonin-2C Receptor Agonist 2012 Phentermine -Topiramate ER Sympathomimetic/Anticonvulsant 2012 Naltrexone SR-Bupropion SR Opioid Receptor Antagonist/ Dopamine and Norepinephrine Reuptake Inhibitor 2014 Liraglutide GLP-1 Agonist 2014

9 FDA Criteria 1. 5% or more decrease in body weight compared to placebo 2. 35% or more study participants lost at least 5% of body weight 3. Benefits outweigh harms

10 Short-Term Use (3 Months) Sympathomimetic Amines: Phentermine Mechanism of Action: Increases satiety Stimulation of Hypothalamus Release norepinephrine

11 Phentermine o Side Effects o Palpitations, tachycardia, increased blood pressure, insomnia, dysphoria o Precautions o CAD, Arrhythmias, Uncontrolled HTN, hyperthyroidism and substance abuse hx o Schedule IV

12 Phentermine Frequently prescribed off label for longer Most widely prescribed Meta Analysis of 6 studies Timeframe: 2 to 24 weeks Total weight loss 6.3 Kg Similar weight loss in continuous vs. intermittent

13 Long-Term Use Orlistat Lorcaserin Phentermine -Topiramate ER Naltrexone - Buproprion ER Liraglutide

14 Orlistat Mechanism of Action o Inhibits 1/3 of fat absorption Side Effects o Common: Gastrointestinal oimproved with Metamucil o Rare: Severe liver disease Precautions o Multi-vitamin Roche Laboratories 2009

15 ~4 kg 1 year Torgerson J S et al. Dia Care 2004;27: Copyright 2014 American Diabetes Association, Inc.

16 Does Orlistat Meet the FDA Standards? 1. 5% or more loss of body weight? No, average 3% 2. 35% or more participants lost at least 5%? Almost 13-34% 3. Benefits outweigh harm? Likely (Yanovski 2013)

17 Eisai Inc Locaserin Mechanism of Action: Selective Serotonin 2C Receptor Agonist

18 Locaserin o Side Effects: Headache, dizziness, fatigue, nausea o Potential drug interactions: Serotonergic or antidopaminergic agents o Warnings- Valvular heart disease, psychiatric disorders, cognitive impairment o Schedule IV

19 Locaserin How to evaluate patient response? After 3 months, is weight loss more than 5% body? Smith et al. 2010

20 Does Locaserin Meet the FDA Standards 1. 5% or more loss of body weight? No, average is 3% 2. 35% or more participants lost at least 5%? No, 25% of participants 3. Benefits outweigh harm? Unsure, post marketing studies

21 Phentermine - Topiramate ER o Mechanism of Action: Appetite Suppression o Side Effects: Paresthesia, dizziness, insomnia, taste alterations o Precautions- Alcohol use, non-potassium sparing diuretics o Contraindication- Glaucoma, Hyperthyroidism, MAOIs o Pregnancy Category X: Cleft Palate o Monthly Pregnancy testing o Schedule IV o Monitoring o CO 2, K +, Glucose

22 SEQUEL Study: Weight Loss Percentage Per BMI Garvey WT, et al. Am J Clin Nutr. 2012;95:

23 Does Phentermine Topiramate ER Meet the FDA Standards? 1. 5% or more loss of body weight? Yes, average of 7% weight loss 2. 35% or more participants lost at least 5%? Yes, 43% lost 5% or more 3. Benefits outweigh harm? Unsure, Postmarketing studies required

24 Naltrexone SR - Bupropion SR Mechanism of Action: Naltrexone: Opioid Antagonist Bupropion: Dopamine and Norepinephrine uptake inhibitor Regulation of food intake Hypothalamus Mesolimbic Dopaminergic Contraindications: Uncontrolled HTN, Seizure disorders, Chronic opioid use, Side effects: Nausea, constipation, headache, vomiting

25 Naltrexone SR Buproprion SR Efficacy (COR-1 Change in Body Weight) Greenway F et al, Lancet. 2010:376 (9741):

26 Naltrexone SR Buproprion SR 1. 5% or more loss of body weight? 2. 35% or more participants lost at least 5%? 3. Benefits outweigh harm? Unsure

27 Liraglutide Mechanism of Action: Insulin sensitizer, GLP-1 Receptor Agonist Originally marketed for diabetes Increased risk of pancreatitis

28 Liraglutide Efficacy with Low Calorie Diet (SCALE Study) Wadden T et al 2013

29 Non- FDA Regulated Supplements Unknown Safety and Efficacy Green Coffee Bean Extract Garcinia Cambogia Raspberry Ketones Unicorn hair, ect