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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
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Overview of Obesity in the U.S.
CDC, NCHS Data brief, No 82, January 2012
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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
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MUST BE REALISTIC
Goals of Therapy
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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
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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
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Drugs than alter fat digestion Seratonin Agonists Sympathomimetic Drugs Antidepressants Hormones Combination Drugs
Pharmacologic therapy
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Orlistat
Orlistat
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Prescription
Pharmacologic therapy
Over the counter
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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
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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.
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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
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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
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Approved by FDA 2012
In addition to reduced calorie diet
BMI >30 BMI >27 with DM,
HTN, cholesterol, OSA
Lorcaserin
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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
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Lorcaserin Efficacy
Smith SR et al. N Engl J Med 2010;363:245-256
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Lorcaserin Efficacy
Smith SR et al. N Engl J Med 2010;363:245-256
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Lorcaserin Efficacy
Smith SR et al. N Engl J Med 2010;363:245-256
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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
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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
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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
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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
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Potential for abuse Approved only for short term use (<12 weeks) Contraindicated
CAD HTN Hyperthyroidism History of drug abuse
Sympathomimetic Drugs
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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
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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.
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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.
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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
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hCG
*
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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.
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FDA approved in 2012 Adults with BMI > 30 or > 27 with at least one
weight related comorbidity
Combination DrugsPhentermine-Topiramate
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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
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Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)
Terms and Conditions
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Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)
Terms and Conditions
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Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)
Terms and Conditions
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Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)
Terms and Conditions
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Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)
Terms and Conditions
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Source: The Lancet 2011; 377:1341-1352 (DOI:10.1016/S0140-6736(11)60205-5)
Terms and Conditions
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Garvey WT, et al. Am J Clin Nutr 2012;95:297.
1.8%
9.3%
10.5%
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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.
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Hyperthyroidism Glaucoma Monamine oxidase inhibitors within 14 days Renal stones (topiramate)
Phentermine-TopiramateContraindications
*
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Increased risk of orofacial clefts
Pregnancy test before start and monthly after
REMS Pharmacy
certification
Phentermine-TopiramateSide Effects
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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
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Peptides Leptin (adipose tissue) Peptide YY (gut hormone) Oxyntomodulin (gut hormone) Melanocortin-4 receptor agonists (hypothalmus)
Sympathomimetic Tesofensine
Experimental Drugs
*
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Diet and lifestyle BMI > 25 or obese >30 should receive counselling on
diet, lifestyle and goals for weight loss
Summary and Recommendations
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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
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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
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http://www.cdc.gov/obesity/childhood/basics.html