Twenty-eight RCTs involving at least 9,919 participants were included.
There was considerable variation in study quality: 2 trials scored two out of five, 19 trials scored three, 5 trials scored four and 2 trials scored five.
Weight loss (15 RCTs, n=9,919 at 1 year).
Significantly more patients treated with orlistat achieved a clinically meaningful weight loss of either 5% (RR 1.66, 95% CI: 1.35, 2.03) or 10% (RR 1.90, 95% CI: 1.39, 2.61) in comparison with those treated with placebo. The mean weight loss after 1 year of follow-up was significantly better in all subgroups of patients (low risk, high risk and diabetic) treated with orlistat than in those treated with placebo. The mean weight loss was also significantly better with orlistat relative to placebo in both the trials with a follow-up of 6 months and 12 weeks.
Serum lipid levels.
At the 1-year follow-up, orlistat had reduced total cholesterol levels, LDL and HDL cholesterol levels, and the ratio of LDL to HDL cholesterol in all patient subgroups compared with placebo (the results were reported). The reductions were statistically significant for all patient subgroups for total cholesterol and LDL cholesterol. Reductions in the ratio of LDL to HDL were statistically significant for obese patients at low risk and high risk. There was no statistically significant difference between orlistat and placebo in HDL cholesterol for obese patients at low or high risk. Triacylglycerols were significantly reduced with orlistat in patients with diabetes. The findings from trials with a follow-up of 6 months were consistent with those from trials with a follow-up of 1 year.
Adverse and gastrointestinal events.
Treatment with orlistat was associated with a significantly higher risk of experiencing at least one gastrointestinal event, compared with placebo, in trials with a treatment duration of 1 year (RR 1.46, 95% CI: 1.37, 1.55). This finding was consistent across subgroups of patients. Similar results were also observed in the trials of 6 months' duration. Twelve trials also reported changes in fat-soluble vitamin concentrations: concentrations of vitamins A, D, E and beta-carotene all decreased more from baseline with orlistat than with placebo, but the differences were not clinically significant.
Funnel plots for weight loss studies suggested the possibility of publication bias. Other results were also reported.