Transcript Obesity Rates Are Projected to Double Over the Next 30 Years

The Obesity/Diabetes Epidemic:
Adiposopathy & ‘Obesity’- The New
Disease!
Weight Management in Obesity and DM:
Emphasis on New Medical Therapies
Part 4
Stan Schwartz MD, FACP, FACE
Private Practice, Ardmore
Obesity Program
Cardiometabolic Diabetes Center and Affiliate,
Main Line Health System
Emeritus, Clinical Associate Professor
University of Pennsylvania
? Explains benefit of Smartphone APPs
DRUGS
Long-Term Pharmacotherapy
• Pharmacotherapy typically used to induce
weight loss but greater benefit may be for
maintenance of weight loss
• Use weight loss medication chronically, in
same manner as medications for other chronic
conditions
• Orlistat, a lipase inhibitor: 8% loss at 2 years
Medications
• Short-term obesity management
• Sympathomimetics (Phentermine, Diethylpropion, Benzphetamine)
• Long-term obesity management
• Lipase inhibitors (Orlistat)
• Recently approved obesity medications
• Serotonin agonists (Locaserin)- BELVIQ
• Combination agents (Phentermine-topiramate)-QSYMIA
Phentermine (Suprenza)
Type: sympathomimetic
Mechanism of action: stimulates the hypothalamus to suppress appetite
Year of approval: 1959
FDA approved indication: short-term (< 12 weeks) adjunct to exercise and caloric restriction for
BMI ≥ 30 or ≥ 27 in the presence of other risk factors such as hypertension, diabetes or
hyperlipidemia
Efficacy: 3.6 kg mean weight loss beyond that achieved by placebo at 2-24 weeks (meta-analysis
of six placebo-controlled trials; Int J Obes Relat Metab Disord 2002;26:262-73)
Adverse effects: risk of dependence and abuse, hypertension, dry mouth, insomnia, tremor, GI
disturbance, primary pulmonary hypertension (rare, associated with combined use of
fenfluramine in “fen-phen”), valvular heart disease (rare), psychosis (rare)
Contraindications: history of CV disease, MAOIs, hyperthyroidism, glaucoma, history of drug
abuse, pregnancy, breastfeeding
Orlistat (Xenical, Alli)
Type: lipase inhibitor
Mechanism of action: inhibits the breakdown of triglycerides into absorbable free fatty acids by
lipase enzymes in the stomach and pancreas, resulting in less fat being absorbed
Year of approval: 1999 (Xenical – prescription 120 mg TID), 2007 (Alli – OTC 60 mg)
FDA approved indication: as an adjunct to a reduced-calorie and low-fat diet for weight loss or to
lower the risk of regaining weight after prior weight loss
Efficacy: 2.9 kg mean weight loss (Xenical) beyond that achieved by placebo at one year (metaanalysis of 15 trials; Ann Intern Med 2005;142:532-46)
Adverse effects: significant diarrhea, fecal incontinence, oily spotting, flatulence, bloating,
dyspepsia (all can be reduced with avoidance of fat-rich foods), reduced absorption of fat-soluble
vitamins, serious liver injury (rare)
Contraindications: malabsorption, cholestasis, impaired liver function, pancreatic disease,
pregnancy (added in 2012)
Lorcaserin (Belviq)
Type: serotonin agonist
Mechanism of action: activates 5-HT2C receptors in the hypothalamus, resulting in increased
proopiomelanocortin (POMC) production, which promotes satiety
Year of approval: 2012
FDA approved indication: treatment of obesity for adults with BMI ≥ 30 or ≥ 27 in the presence
of other risk factors such as hypertension, diabetes or hyperlipidemia
Efficacy: 3.6 kg mean weight loss beyond that achieved by placebo (5.8 kg vs. 2.2 kg) at one year
(Phase 3 RCT; N Engl J Med 2010; 363:245-256)
Adverse effects: headache, nasopharyngitis
Contraindications: pregnancy, MAOIs, SSRIs (caution)
Phentermine-topiramate (Qsymia)
Year of approval: 2012
FDA approved indication: chronic weight management, as an adjunct to a reduced-calorie diet
and exercise, for BMI ≥ 30 or ≥ 27, in the presence of other risk factors such as hypertension,
diabetes or hyperlipidemia
Efficacy: 10.7 kg mean weight loss beyond that achieved by placebo (12.6 kg vs. 1.9 kg) at one
year (Phase 3 RCT; Obesity (2012); 20 2, 330–342)
Adverse effects: tachycardia, insomnia, paresthesias, dizziness, distorted taste sensation,
constipation, dry mouth, anxiety, suicidality (rare), acute angle closure glaucoma (rare), metabolic
acidosis (rare), increased serum creatinine (rare)
Contraindications: pregnancy, glaucoma, hyperthyroidism, MAOIs, history of suicide attempt
Comparative Drug Efficacy