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Long-term Drug Treatment for Obesity:  A Systematic and Clinical Review

Susan Z. Yanovski, MD1; Jack A. Yanovski, MD, PhD2
[+] Author Affiliations
1Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
2Section on Growth and Obesity, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
JAMA. 2014;311(1):74-86. doi:10.1001/jama.2013.281361.
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Importance  Thirty-six percent of US adults are obese, and many cannot lose sufficient weight to improve health with lifestyle interventions alone.

Objective  To conduct a systematic review of medications currently approved in the United States for obesity treatment in adults. We also discuss off-label use of medications studied for obesity and provide considerations for obesity medication use in clinical practice.

Evidence Review  A PubMed search from inception through September 2013 was performed to find meta-analyses, systematic reviews, and randomized, placebo-controlled trials for currently approved obesity medications lasting at least 1 year that had a primary or secondary outcome of body weight change, included at least 50 participants per group, reported at least 50% retention, and reported results on an intention-to-treat basis. Studies of medications approved for other purposes but tested for obesity treatment were also reviewed.

Findings  Obesity medications approved for long-term use, when prescribed with lifestyle interventions, produce additional weight loss relative to placebo ranging from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92 mg) phentermine plus topiramate–extended release at 1 year. The proportion of patients achieving clinically meaningful (at least 5%) weight loss ranges from 37% to 47% for lorcaserin, 35% to 73% for orlistat, and 67% to 70% for top-dose phentermine plus topiramate–extended release. All 3 medications produce greater improvements in many cardiometabolic risk factors than placebo, but no obesity medication has been shown to reduce cardiovascular morbidity or mortality. Most prescriptions are for noradrenergic medications, despite their approval only for short-term use and limited data for their long-term safety and efficacy.

Conclusions and Relevance  Medications approved for long-term obesity treatment, when used as an adjunct to lifestyle intervention, lead to greater mean weight loss and an increased likelihood of achieving clinically meaningful 1-year weight loss relative to placebo. By discontinuing medication in patients who do not respond with weight loss of at least 5%, clinicians can decrease their patients’ exposure to the risks and costs of drug treatment when there is little prospect of long-term benefit.

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Figure.
Identification of Manuscripts for Systematic Review

A PubMed search was conducted from inception to September 15, 2013, to find long-term (≥1-y) placebo-controlled randomized clinical trials and meta-analyses investigating drugs currently US Food and Drug Administration–approved alone or in combination for an obesity or weight-management indication.aRandomized controlled trials (RCTs) were excluded for the following reasons: nonapproved drug or drug combination, participants were children, not published in English, no placebo group, did not meet criteria for size, duration, or attrition, not an intention-to-treat analysis, or insufficient description of data analysis. Many studies had more than 1 exclusion criterion.

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