Orlistat and Sibutramine for Obesity and Overweight

A Cochrane review [Abstract] 1 included eleven orlistat weight loss studies with 7 180 subjects and five sibutramine studies with 1 556 subjects (three weight loss and two weight maintenance trials) of at least one-year duration. 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 to 4.9) 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. Interpretation of the results is limited by high attrition rates which averaged 33% during the weight loss phase of orlistat trials and 43% in sibutramine studies.

The effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation were estimated in a population-based cohort study 2 in United Kingdom. Each patient receiving orlistat or sibutramine was matched with up to 5 obese patients receiving neither drug (100 701 with orlistat, 15 355 with sibutramine and 508 140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m, respectively). Weight loss with orlistat was, on average, 0.94 kg month (95% CI 0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month (95% CI 1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month.

Clinical comment: Sibutramine was suspended from market in January 2010 due to an increase of cardiovascular risk.

Comment: The quality of evidence is downgraded by study quality (more than 20% loss to follow up).

References

• Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev 2004;2003(3):CD004094 [PubMed]
• Douglas IJ, Bhaskaran K, Batterham RL et al. The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population-based cohort. Br J Clin Pharmacol 2015;79(6):1020-7. [PubMed]