Medical Management
of Obesity
Farah Hasan MD, FRCP,
FACE
Section Chief, Endocrinology
Advocate Christ Medical Center
Clinical Assistant Professor UIC
Overview of Obesity in the U.S.
CDC, NCHS Data brief, No 82, January 2012
Prevalence* of Self-Reported Obesity Among U.S. Adults 2012
BRFSS, 2012
*
15-20%
20-25%
Behavioral risk factor surveillance system, CDC
25-30%
30-35%
>35%
Goals of Therapy
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***
*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
Approach

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
Pharmacologic therapy

Drugs than alter fat digestion

Seratonin Agonists

Sympathomimetic Drugs

Antidepressants

Hormones

Combination Drugs
Orlistat
Pharmacologic therapy
Prescription
Over the counter
Orlistat Efficacy

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
*Leblanc ES, et al. Ann Intern Med 2011; 155:434
Orlistat Efficacy

37% reduction in conversion to diabetes from IGT*

Improves systolic and diastolic blood pressure**

Improves serum lipids***
*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.
Orlistat Side effects


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**
*Padwal R, et al. Cochrane Database Syst Rev 2004;:CD004094
**Courtney AE, et al. Nephrol Dial Transplant 2007;22:621
Serotonin Agonists



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
*Padwal R, et al. Cochrane Database Syst Rev 2004;:CD004094
**Courtney AE, et al. Nephrol Dial Transplant 2007;22:621
Lorcaserin




Approved by FDA
2012
In addition to reduced
calorie diet
BMI >30
BMI >27 with DM,
HTN, cholesterol,
OSA
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
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
Locaserin Efficacy


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**
*Smith SR et al. N Engl J Med 2010;363:245-256
**O’Neil, et al. Obesity 2012;20:1426
Locaserin Side Effects


Headache, URI, nasopharyngitis, dizziness, nausea
No significant increase in serotonin associated
valvulopathy by echo at 52 weeks
*Smith SR et al. N Engl J Med 2010;363:245-256
Locaserin Dosing



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
FDA Highlights of prescrbing information :BELVIQ. http://www.accessdata.fda.gov
Sympathomimetic Drugs

Stimulate the release of norepi or inhibit reuptake


Block norepi and serotonin reuptake


Sibutramine (Meridia, withdrawn from market)
Directly act on adrenergic receptors


Phenteramine, diethylpropion, benzphetamine,
phendimetrazine
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 Efficacy


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**
*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
Sympathomimetic Drugs Side Effects



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**
*FDA Drug Safety Communication, http://www.fda.gov/Drugs
**Kernan WN, et al. NEJM 2000;343:1826.
Sympathomimetic Drugs Ephedra/Ma Huang




Prolonged duration
of action
Found in plants
 thermagenesis and 
food intake
Not approved for
obesity treatment and
removed from
market*
*Shekelle PG, et al. JAMA 2003;289:1537.
Antidepressants


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**
*Gadde KM, et al. Obes Res 2001;9:544
**Anderson JW, et al. Obes Res 2002;10:633
hCG
*
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*
*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.
Combination Drugs
Phentermine-Topiramate


FDA approved in 2012
Adults with BMI > 30 or > 27 with at least one
weight related comorbidity
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 1341-1352 (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
1.8%
9.3%
10.5%
Garvey WT, et al. Am J Clin Nutr 2012;95:297.
Phentermine-Topiramate
Side Effects

Dry mouth

Constipation

Paresthesia

Depression

Anxiety

Increased heart rate
*FDA Drug Safety Communication, http://www.fda.gov/Drugs
**Kernan WN, et al. NEJM 2000;343:1826.
Phentermine-Topiramate
Contraindications
*

Hyperthyroidism

Glaucoma

Monamine oxidase inhibitors within 14 days

Renal stones (topiramate)
Phentermine-Topiramate
Side Effects




Increased risk
of orofacial
clefts
Pregnancy test
before start and
monthly after
REMS
Pharmacy
certification
Phentermine-Topiramate
Dosing




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
*http://www.fda.gov/downloads/Drugs/Drugsafety/Postmarketdurgsafetyinformationforpatientsandproviders
Experimental Drugs


Peptides

Leptin (adipose tissue)

Peptide YY (gut hormone)

Oxyntomodulin (gut hormone)

Melanocortin-4 receptor agonists (hypothalmus)
Sympathomimetic

*
Tesofensine
Summary and Recommendations

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
http://www.cdc.gov/obesity/childhood/basics.html