Prescription Drug Treatment for Obesity
Abstract & Commentary
By Mary Elina Ferris, MD, Clinical Associate Professor, University of Southern California. Dr. Ferris reports no financial relationship to this field of study.
Synopsis: A review of 79 clinical trials involving diet plus medications for treating obesity with BMI > 27 found modest weight loss at 1 year with sibutramine, orlistat, phentermine, bupropion, and topiramate when compared to placebo pills, and probably also for diethylpropion and fluoxetine.
Source: Li Z, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005:142;532-546.
As part of a larger evidence report for the Agency for Healthcare Research and Quality on both pharmacologic and surgical treatment of obesity, an extensive literature search and analysis was conducted for the following drugs chosen by a technical expert panel: sibutramine, orlistat, phentermine, diethylpropion (all approved by the FDA for weight loss), and also fluoxetine, bupropion, sertraline, topiramate, and zonisamide. All are appetite suppressants except orlistat which is a lipase inhibitor. Fluoxetine and sertraline are SSRIs, bupropion is another antidepressant type (norepinephrine and dopamine receptors), and topiramate and zonisamide were first approved as anticonvulsants.
Starting with 1064 articles, 79 were analyzed which met the criteria of controlled clinical trials with BMI > 27 and at least 6-month outcomes. Medications were always combined with diet and sometimes exercise. All but one assessed the efficacy of the medications compared to placebo; the exception compared head-on the medications sibutramine, orlistat, and metformin and all reported significant weight loss of 8-13 kg, with the sibutramine group losing 4-5 kg more than the other groups.
Sibutramine, orlistat, and phentermine had the strongest supporting data, and probably diethylpropion, fluoxetine, bupropion and topiramate were also effective for weight loss at 6 months compared to placebo when combined with diet. The most studied and strongest supported was sibutramine with mean weight changes of -4.45 kg, and orlistat with -2.75 kg. Phentermine had changes of -3.6 kg, diethylpropion -3 kg, and bupropion -2.77 kg. Fluoxetine had ranges from -14.5 kg to +0.4 kg, and was used in larger doses (60 mg) than those for depression. Topiramate was reported as 6.5% of pretreatment weight lost.
Significant side effects were reported for all drugs: orlistat with GI side effects, sibutramine with increase in heart rate and blood pressure, phentermine with both cardiovascular and GI side effects, fluoxetine with GI effects, agitation and nervousness, bupropion with paresthesias and insomnia, and topiramate with paresthesias and taste changes.
The weakest data were for zonisamide and sertraline where only one acceptable study each was identified; zonisamide had a 5% increased weight loss compared to placebo, but for sertraline there was no significant difference between drug and placebo.
Commentary
This summary of drug treatment for obesity provides a much-needed scientific approach to the management of this epidemic problem. It confirms probable efficacy for modest weight loss for at least 7 drugs when used in combination with diet. Unfortunately current evidence does not support any one particular drug as more effective, so the choice of drug will most likely be determined by individual tolerance to the particular side effect profile.
This study is accompanied in the same issue by a similar meta-analysis for surgical treatment of obesity,1 and by a new Clinical Practice Guideline from the American College of Physicians (ACP)2 for the management of obesity in primary care.
The new guidelines were developed for obese patients with BMI > 30, and they begin with the US Preventive Services Task Force recommendations for diet and exercise and individualized goal determination. If weight loss is insufficient, the guidelines suggest that patients should be offered pharmacologic therapy after a discussion of risks, benefits and lack of long-term safety data, along with continued promotion of diet and exercise. The drugs recommended by the ACP are sibutramine, orlistat and phentermine, diethylpropion, fluoxetine, and bupropion. While topiramate and zonisamide have shown weight loss, the number of published studies was considered too small for them to be included.
Although the findings of only a mean additional benefit of 5 kg loss with medications were disappointing, the ACP notes that studies support the benefit on comorbid illnesses of even modest 5-10% weight loss, such as reductions in HTN, lipid levels and decreased progression of impaired glucose tolerance to type 2 diabetes.
Finally, surgical treatment for obesity at high-volume centers is recommended when the BMI is > 40, comorbid illnesses are present, and patients have failed an adequate diet and exercise program, with or without adjunctive drug therapy. Unfortunately, these surgeries have not been shown to reduce cardiovascular morbidity, and there is not enough evidence at present to recommend one procedure over another.
References
1. Maggard MA, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med. 2005;142:547-559.
2. Snow V, et al. Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2005;142:525-531.
A review of 79 clinical trials involving diet plus medications for treating obesity with BMI > 27 found modest weight loss at 1 year with sibutramine, orlistat, phentermine, bupropion, and topiramate when compared to placebo pills, and probably also for diethylpropion and fluoxetine.
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