1. Farah Hasan MD, FRCP, FACE Section Chief, Endocrinology Advocate Christ Medical Center Clinical Assistant Professor UIC Medical Management of Obesity

2. Overview of Obesity in the U.S. CDC, NCHS Data brief, No 82, January 2012

3. Prevalence * of Self-Reported Obesity Among U.S. Adults 2012 BRFSS, 2012 * 15-20% 20-25%25-30%30-35%>35% Behavioral risk factor surveillance system, CDC

9. MUST BE REALISTIC Goals of Therapy

10.  Ideal is a return to normal body weight  Not realistic*  Degree of weight loss  First month 2 kg  3-6 mos 5-10% TBW  Improvement in risk factors  Diabetes**  Cardiovascular disease*** Goals of Therapy *Foster, et al. J Consult Clin Psychol 1997;65:79 **Knowler, et al. NEJM 2002;346:393. ***Douketis, et al. Int J Obes 2005; 29:1153

11.  Counsel all BMI >25  Diet, lifestyle and goal for weight loss  Pharmacologic therapy  BMI >30 or BMI >27 with comorbidities  Failed diet and exercise alone Approach

12. Drugs than alter fat digestion Seratonin Agonists Sympathomimetic Drugs Antidepressants Hormones Combination Drugs Pharmacologic therapy

14. OrlistatOrlistat Orlistat

15. Prescription Pharmacologic therapy Over the counter

16.  Meta analysis of 12 trials*  Orlistat + behaviour -5-10 kg (8%TBW)  Placebo +behaviour -3-6 kg  Difference of 3 kg  Maintained for 24 to 23 months Orlistat Efficacy *Leblanc ES, et al. Ann Intern Med 2011; 155:434

18.  37% reduction in conversion to diabetes from IGT*  Improves systolic and diastolic blood pressure**  Improves serum lipids*** Orlistat Efficacy *Togerson JS, et al. XENDOS study. Diabetes Care 2004;27:155. **Siebenhofer A, et al. Cochrane Database Syst Rev 2013;3:CD007654. ***Davidson MH, et al. JAMA 1999;281:235.

20.  15-30% GI side effects*  Cramps, fecal incontinence, oily spotting, flatus  Can be avoided with diet <30% fat  Malabsorption of fat soluble vitamins  ADEK and beta-carotene  Give vitamin supplements  Severe Liver injury Rare  Oxalate induced kidney injury** Orlistat Side effects *Padwal R, et al. Cochrane Database Syst Rev 2004;:CD004094 **Courtney AE, et al. Nephrol Dial Transplant 2007;22:621

21.  Serotonin reduces food intake  Lorcaserin is a selective agonist of the serotonin 2C receptor  Nonselective serotonergic agonists such as fenfluramine and dexfenfluramine enhanced weight loss but increased risk of valvular heart disease through serotonin receptor 2B Serotonin Agonists *Padwal R, et al. Cochrane Database Syst Rev 2004;:CD004094 **Courtney AE, et al. Nephrol Dial Transplant 2007;22:621

22.  Approved by FDA 2012  In addition to reduced calorie diet  BMI >30  BMI >27 with DM, HTN,  cholesterol, OSA Lorcaserin

23. Original Article Multicenter, Placebo-Controlled Trial of Lorcaserin for Weight Management Steven R. Smith, M.D., Neil J. Weissman, M.D., Christen M. Anderson, M.D., Ph.D., Matilde Sanchez, Ph.D., Emil Chuang, M.D., Scott Stubbe, M.B.A., Harold Bays, M.D., William R. Shanahan, M.D., and the Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group N Engl J Med Volume 363(3):245-256 July 15, 2010

24. Lorcaserin Efficacy Smith SR et al. N Engl J Med 2010;363:245-256

25. Lorcaserin Efficacy Smith SR et al. N Engl J Med 2010;363:245-256

26. Lorcaserin Efficacy Smith SR et al. N Engl J Med 2010;363:245-256

27.  Beneficial effects on surrogate markers*  Slight decrease in BP  Heart rate  Total and LDL cholesterol  CRP, fibrinogen, fasting glucose and insulin levels  Beneficial effect on A1c and and fasting glucose in patients with DM** Locaserin Efficacy *Smith SR et al. N Engl J Med 2010;363:245-256 **O’Neil, et al. Obesity 2012;20:1426

28.  Headache, URI, nasopharyngitis, dizziness, nausea  No significant increase in serotonin associated valvulopathy by echo at 52 weeks Locaserin Side Effects *Smith SR et al. N Engl J Med 2010;363:245-256

29.  10 mg BID  Response to therapy should be evaluated by week 12  Discontinue if patients do not lose 5% of body weight in 12 weeks*  Do not use if individuals with CrCL<30  Do not use in pregnancy  Do not use with other SSRI, SNRI, TCA’s, MAOI’s Locaserin Dosing FDA Highlights of prescrbing information :BELVIQ. http://www.accessdata.fda.gov

30.  Stimulate the release of norepi or inhibit reuptake  Phenteramine, diethylpropion, benzphetamine, phendimetrazine  Block norepi and serotonin reuptake  Sibutramine (Meridia, withdrawn from market)  Directly act on adrenergic receptors  Phenylpropanolamin (withdrawn from market)  May increase blood pressure Sympathomimetic Drugs

31.  Potential for abuse  Approved only for short term use (<12 weeks)  Contraindicated  CAD  HTN  Hyperthyroidism  History of drug abuse Sympathomimetic Drugs

32.  Average weight loss for 4 weeks was 0.23 kg/wk more than placebo*  In trials up to 25 weeks duration net weight loss with diethylpropion compared to placebo ranged from 1-10 kg** Sympathomimetic Drugs Efficacy *Scoville BA, et al. Obesity in Perspective. DHEW Pub No. (NIH 75-708). 1975:441-3 **Bray GA, et al. Ann Intern Med 1993;119:707

34.  Increased heart rate, HTN, insomnia, dry mouth, constipation, nervousness  Sibutramine was withdrawn from the market for increased risk of MI and non fatal stroke*  Phenylpropanoloamine was removed for increased risk of hemorrhagic stroke** Sympathomimetic Drugs Side Effects *FDA Drug Safety Communication, http://www.fda.gov/Drugs **Kernan WN, et al. NEJM 2000;343:1826.

35.  Prolonged duration of action  Found in plants   thermagenesis and  food intake  Not approved for obesity treatment and removed from market* Sympathomimetic Drugs Ephedra/Ma Huang *Shekelle PG, et al. JAMA 2003;289:1537.

36.  Increase body weight, weight neutral or reduce weight  Bupropion is approved for prevention of weight gain when trying to stop smoking  Relative of diethylpropion  Likely acts by modulating norepi*  6 mos trial of bupropion vs placebo resulted in more weight loss** Antidepressants *Gadde KM, et al. Obes Res 2001;9:544 **Anderson JW, et al. Obes Res 2002;10:633

38. hCG *

39.  Advertized to aid in weight loss  No evidence for IM, oral or sublingual drops  Several randomized trials have shown that the hCG diet is not more effective than placebo*  Integral component of the diet is 200-800 calorie diet* hCG *Greenway, et al. West J Med 1977; 127:461 **Bosch B, et al. S Afr Med J 1990; 77:185. ***Stein MR, et al. Am J Clin Nutr 1976; 29:940.

40.  FDA approved in 2012  Adults with BMI > 30 or > 27 with at least one weight related comorbidity Combination Drugs Phentermine-Topiramate

41. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial Kishore M Gadde, MD, David B Allison, PhD, Donna H Ryan, MD, Craig A Peterson, MS, Barbara Troupin, MD, Michael L Schwiers, MS and Wesley W Day, PhD The Lancet Volume 377, Issue 9774, Pages 1341-1352Volume 377, Issue 9774, Pages 1341-1352 (April 2011) DOI: 10.1016/S0140-6736(11)60205-5 Copyright © 2011 Elsevier Ltd Terms and ConditionsTerms and Conditions

42. Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)The Lancet 2011; 377:1341-1352 Terms and Conditions

43. Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)The Lancet 2011; 377:1341-1352 Terms and Conditions

44. Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)The Lancet 2011; 377:1341-1352 Terms and Conditions

45. Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)The Lancet 2011; 377:1341-1352 Terms and Conditions

46. Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)The Lancet 2011; 377:1341-1352 Terms and Conditions

47. Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)The Lancet 2011; 377:1341-1352 Terms and Conditions

48. Garvey WT, et al. Am J Clin Nutr 2012;95:297. 1.8% 9.3% 10.5%

49.  Dry mouth  Constipation  Paresthesia  Depression  Anxiety  Increased heart rate Phentermine-Topiramate Side Effects *FDA Drug Safety Communication, http://www.fda.gov/Drugs **Kernan WN, et al. NEJM 2000;343:1826.

50.  Hyperthyroidism  Glaucoma  Monamine oxidase inhibitors within 14 days  Renal stones (topiramate) Phentermine-Topiramate Contraindications *

51.  Increased risk of orofacial clefts  Pregnancy test before start and monthly after  REMS  Pharmacy certification Phentermine-Topiramate Side Effects

52.  Initial dose 3.75/23 mg for 14 days, followed by 7.5/46 mg*  Increase to 11.25/69 after 12 weeks if 3% body weight loss not achieved for 14 days and then to 15/92 mg  If weight loss of 5% not achieved after 12 weeks on the highest dose, taper off medication gradually  Abrupt withdrawl can cause seizures Phentermine-Topiramate Dosing *http://www.fda.gov/downloads/Drugs/Drugsafety/Postmarketdurgsafetyinformationforpatientsandproviders

54.  Peptides  Leptin (adipose tissue)  Peptide YY (gut hormone)  Oxyntomodulin (gut hormone)  Melanocortin-4 receptor agonists (hypothalmus)  Sympathomimetic  Tesofensine Experimental Drugs *

55.  Diet and lifestyle  BMI > 25 or obese >30 should receive counselling on diet, lifestyle and goals for weight loss Summary and Recommendations

57.  Pharmacotherapy BMI >30 or >27 with comorbidities Orlistat as first line given excellent CV safety profile, and benefits on lipids Use for 2-4 years Lorcaserin for those who can not tolerate orlistat Few longterm safety data Discontinue if <5% body weight loss at 12 weeks Summary and Recommendations

58.  Phenteramine-topiramate for obese men and postmenopausal women without HTN or CAD  Caution in women of childbearing age  Discontinue if <5% body weight loss after 12 weeks on highest dose  Discontinue gradually Summary and Recommendations

60. http://www.cdc.gov/obesity/childhood/basics.html