Long-term pharmacotherapy for obesity and overweight.
BACKGROUND
Worldwide prevalence rates of obesity and overweight are rising and safe and effective treatment strategies are urgently needed. A number of anti-obesity agents have been studied in short-term clinical trials, but long-term efficacy and safety need to be established.


OBJECTIVE
To assess/compare the effects and safety of approved anti-obesity medications in clinical trials of at least one-year duration.


METHODS
MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Current Science Meta-register of Controlled Trials, and reference lists of original studies and reviews were searched. Date of last search was December 2002. Drug manufacturers and two obesity experts were contacted in to detect unpublished trials. No language restrictions were imposed.


METHODS
Double-blind, randomised controlled weight loss and weight maintenance trials of approved anti-obesity agents that 1) enrolled adult overweight or obese patients, 2) included a placebo control group or compared two or more anti-obesity drugs 3) used an intention-to-treat analysis, and 4) had a minimum follow-up period of one year. Abstracts and pseudo-randomised trials were not included.


METHODS
Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measure was weight loss.


RESULTS
Of the eight anti-obesity agents investigated, only orlistat and sibutramine trials met inclusion criteria. Eleven orlistat weight loss studies (four of which reported a second year weight maintenance phase) and five sibutramine studies (three weight loss and two weight maintenance trials) were included. Attrition rates averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies. All patients received lifestyle modification as a co-intervention. Compared to placebo, orlistat-treated patients lost 2.7 kg (95% CI: 2.3 kg to 3.1 kg) or 2.9% (95% CI: 2.3 % to 3.4%) more weight and patients on sibutramine experienced 4.3 kg (95% CI: 3.6 kg to 4.9 kg) or 4.6% (95% CI: 3.8% to 5.4%) greater weight loss. The number of patients achieving ten percent or greater weight loss was 12% (95% CI: 8% to 16%) higher with orlistat and 15% (95% CI: 4% to 27%) higher with sibutramine therapy. Weight loss maintenance results were similar. Orlistat caused gastrointestinal side effects and sibutramine was associated with small increases in blood pressure and pulse rate.


CONCLUSIONS
Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.
Padwal
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Division of Clinical Pharmacology, Sunnybrook and Women's College Health Sciences Center, Room E2-42, 2075 Bayview Avenue, Toronto, Ontario, Canada, M4N 3M5.
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D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001067:Appetite Depressants / Q000009:adverse effects / Q000627:therapeutic use; D001835:Body Weight; D003503:Cyclobutanes / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy*; D000077403:Orlistat; D016032:Randomized Controlled Trials as Topic; D015431:Weight Loss
D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D003503:Cyclobutanes; D007783:Lactones; D000077403:Orlistat; C058254:sibutramine