Farah Farah Hasan MD, FRCP, Hasan MD, FRCP, FACEFACE

Section Chief, EndocrinologySection Chief, EndocrinologyAdvocate Christ Medical CenterAdvocate Christ Medical CenterClinical Assistant Professor UICClinical Assistant Professor UIC

Medical Management of Obesity

Medical Management of Obesity

Overview of Obesity in the U.S.

CDC, NCHS Data brief, No 82, January 2012

Prevalence* of Self-Reported Obesity Among U.S. Adults 2012BRFSS, 2012

*

15-20% 20-25% 25-30% 30-35% >35%

Behavioral risk factor surveillance system, CDC

MUST BE REALISTIC

Goals of Therapy

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

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

Drugs than alter fat digestion Seratonin Agonists Sympathomimetic Drugs Antidepressants Hormones Combination Drugs

Pharmacologic therapy

Orlistat

Orlistat

Prescription

Pharmacologic therapy

Over the counter

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

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.

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

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

Approved by FDA 2012

In addition to reduced calorie diet

BMI >30 BMI >27 with DM,

HTN, cholesterol, OSA

Lorcaserin

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 MedVolume 363(3):245-256

July 15, 2010

Lorcaserin Efficacy

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

Lorcaserin Efficacy

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

Lorcaserin Efficacy

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

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

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

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

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

Potential for abuse Approved only for short term use (<12 weeks) Contraindicated

CAD HTN Hyperthyroidism History of drug abuse

Sympathomimetic Drugs

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

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.

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.

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

hCG

*

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.

FDA approved in 2012 Adults with BMI > 30 or > 27 with at least one

weight related comorbidity

Combination DrugsPhentermine-Topiramate

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 LancetVolume 377, Issue 9774, Pages 1341-1352 (April 2011)

DOI: 10.1016/S0140-6736(11)60205-5

Copyright © 2011 Elsevier Ltd Terms and Conditions

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

Terms and Conditions

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

Terms and Conditions

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

Terms and Conditions

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

Terms and Conditions

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

Terms and Conditions

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

Terms and Conditions

Garvey WT, et al. Am J Clin Nutr 2012;95:297.

1.8%

9.3%

10.5%

Dry mouth Constipation Paresthesia Depression Anxiety Increased heart rate

Phentermine-TopiramateSide Effects

*FDA Drug Safety Communication, http://www.fda.gov/Drugs**Kernan WN, et al. NEJM 2000;343:1826.

Hyperthyroidism Glaucoma Monamine oxidase inhibitors within 14 days Renal stones (topiramate)

Phentermine-TopiramateContraindications

*

Increased risk of orofacial clefts

Pregnancy test before start and monthly after

REMS Pharmacy

certification

Phentermine-TopiramateSide Effects

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-TopiramateDosing

*http://www.fda.gov/downloads/Drugs/Drugsafety/Postmarketdurgsafetyinformationforpatientsandproviders

Peptides Leptin (adipose tissue) Peptide YY (gut hormone) Oxyntomodulin (gut hormone) Melanocortin-4 receptor agonists (hypothalmus)

Sympathomimetic Tesofensine

Experimental Drugs

*

Diet and lifestyle BMI > 25 or obese >30 should receive counselling on

diet, lifestyle and goals for weight loss

Summary and Recommendations

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

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

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