Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Safe and effective strategies to curb rising obesity prevalence rates are urgently needed and medications may play a more prominent role in future therapeutic regimens.


OBJECTIVE
To review systematically the long-term efficacy and safety of approved antiobesity medications.


METHODS
MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Drug manufacturers and two obesity experts were contacted. No language restrictions were imposed.


METHODS
Double-blind, randomized controlled studies of approved antiobesity medications with follow-up periods of 1 y or greater were eligible for inclusion.


METHODS
Two reviewers independently assessed all potentially relevant studies for inclusion and methodological quality using standardized abstraction forms.


RESULTS
A total of 11orlistat (n=6021) and three sibutramine (n=929) studies met inclusion criteria. Attrition rates averaged 33% in orlistat studies and 48% in sibutramine studies. A random effects model was used for meta-analysis. Compared to placebo, orlistat-treated patients displayed a 2.7 kg (95% CI: 2.3-3.1 kg) or 2.9% (95% CI: 2.3-3.4%) greater reduction in weight and patients on sibutramine displayed a 4.3 kg (95% CI: 3.6-4.9 kg) or 4.6% (95% CI: 3.8-5.4%) greater weight reduction after 1 y of follow-up. The number of patients achieving 10% or greater weight loss was 12% (95% CI: 8-16%) higher with orlistat and 15% (95% CI: 4-27%) higher with sibutramine compared to placebo. Orlistat caused gastrointestinal side effects and sibutramine increased blood pressure and pulse rate.


CONCLUSIONS
There is a relative paucity of long-term studies of antiobesity agents. In weight loss trials of 1-y duration, orlistat and sibutramine appear modestly effective in promoting weight loss. Longer, more methodologically rigorous studies that are powered to examine end points such as mortality and cardiovascular morbidity are required.
Padwal
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Division of Internal Medicine, University of Alberta Hospital, 2E3. Walter C Mackenzie Health Sciences Centre, Edmonton, AB, Canada. rpadwal@yahoo.com
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D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D003503:Cyclobutanes / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy*; D000077403:Orlistat; D016032:Randomized Controlled Trials as Topic
D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D007783:Lactones; D000077403:Orlistat; C058254:sibutramine