1. Beyond Dieting: New Weight Loss Medications & Treatments on the Horizon Daniel Bessesen, MD

2. Currently Available Options Accept weight where it is Diet/Exercise: 3-10% weight loss Drugs: 5-12% weight loss Medically Supervised/Combination of Diet + Drug: 10-15% weight loss Surgery: 15-30% weight loss Low High Effectiveness

3. Currently Available Options Accept weight where it is Diet/Exercise: 3-10% weight loss Drugs: 5-12% weight loss Medically Supervised/Combination of Diet + Drug: 10-15% weight loss Surgery: 15-30% weight loss Low High Risks/Time/Money

4. A Guide to Selecting Treatment Treatment Body Mass Index category 25-26.927-29.930-34.935-39.9  40 Diet, physical activity, and behavior therapy Pharmacotherapy Surgery With co-morbidity With co-morbidity With co-morbidity + + + + + + ++ NIH The Practical Guide. 2000 http://www.nhlbi.nih.gov/guidelines/obesity/ob_gdlns.htm 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee.citation

5. Obesity Treatment Pyramid Surgery Pharmacotherapy Lifestyle Modification Diet Physical Activity

6. PharmacologicalTreatment of Obesity Current medications 5-12% wt loss Benefits only last as long as patient takes the medication. Chronic treatment likely needed. Drugs probably not paid for by insurance so cost is a big issue for patients. Issues of FDA approval, long term safety, and efficacy. Are medications an appropriate treatment modality for obesity?

7. New and Emerging Medications FDA approved –Lorcasarin (Belviq) –Phentermine/topiramate ER (Qsymia) May be approved in near future –Liraglutide –Bupropion/naltrexone

8. Lorcasarin (Belviq) Serotonin 2C receptor agonist Previous serotonin agonists fenfluramine and dexfenfluramine caused cardiac valve disease, removed from market 2C receptor only in the brain not in heart Studies in 1-2,000 people for up to 2 years do not show evidence if valvulopathy with lorcasarin.

9. Lorcasarin (Belviq) Weight loss: 3-5% no better than phentermine or orlistat Side effects: headache, dizziness and nausea Cost: $220/month Unclear if physicians will prescribe off label with phentermine (no data on safety or efficacy)

10. Lorcasarin: Weight Effects N Engl J Med. 2010 Jul 15;363(3):245-56

11. Phentermine/Topiramate Combination gives greater effectiveness with fewer side effects Cost: $150.00/month Side effects: dry mouth, numbness, tingling, insomnia, dizziness, anxiety, irritability and disturbance in attention

12. Lancet. 2011 Apr 16;377(9774):1341-52 Topiramate/Phentermine (Qsymia) Effects on Weight

13. Phentermine/Topiramate Risk of birth defects: women need – pregnancy test on starting and monthly while using. Reduces blood pressure, glucose, insulin, triglycerides and raises HDL Unclear if physicians will prescribe off label using generic phentermine and topiramate. Most effective medication available 10- 12% weight loss.

14. Gastric Bypass Lap Band Effectiveness Risk Low High

15. Comparison of Operations Lap band: 20% weight loss, very low mortality, 1% serious or 2.4% any complication Sleeve gastrectomy: 25% weight loss, 0.1% mortality, 2.4% serious or 6.3% any complication Gastric bypass: 30% weight loss, 0.2% mortality, 2.5% serious or 10% any complication Ann Surg 2013;257: 791–797; Flum DR, N Engl J Med. 2009 Jul 30;361(5):445-54

16. Benefits of Weight Loss Surgery the Swedish Obese Subjects Trial Bariatric Surgery vs. Usual Care Nonrandomized prospective controlled study 2010 pts. had surgery compared to 2037 contemporaneously matched controls Began 1987 Median follow up 14.7 years

17. Weight loss in the SOS JAMA. 2012;307(1):56-65

18. Bariatric Surgery is Associated with a Reduced Mortality: the SOS Study Sjostrom L NEJM 2007: 357-741-752 30% lower risk Of dying MI: 25 in control Group 13 in the Surgery group Cancer: 47 in The control group 29 in the surgery group

19. Benefits of Bariatric Surgery for T2DM N Engl J Med 2012;366:1567-76 150 patients randomized to intensive medical therapy, gastric bypass or sleeve gastrectomy for management of type 2 diabetes Average baseline A1C was 9.2% (diabetes >6.5, goal <7%) Followed for 12 months

20. Stampede Trial: Benefits of Surgery for Type 2 Diabetes ParameterMedical Therapy (n=41) Bypass (n=50) Sleeve (n=49) P Value HbA1c<612%42%37%0.008 HbA1C<6 without DM med 0%42%27%0.003 % change in Tg-14%-44%-42%0.08 % change in HDL11%28% 0.001 N Engl J Med 2012;366:1567-76

21. Who is a Good Candidate? BMI>35 with co-morbidities or >40 without Age 20-60 Co-morbidities: Diabetes, sleep apnea, reflux > Hypertension, DJD Failed other forms of therapy No serious, active cardiac, pulmonary, or psychiatric disease

22. Thank you