BACKGROUND: Trials of weight-loss drugs indicate some benefits on lipids, blood glucose, or blood pressure levels. Since obesity is associated with increased cardiovascular (CV) medication use and pharmaceutical costs, weight-loss drug use could beeficially impact CV medication use. OBJECTIVE: We examined the temporal associations between CV drugs use 3 years before and after the initiation of orlistat, a weight-loss drug. DESIGN: An historical cohort study in the PHARMO pharmacy registry among new users of orlistat, who were in the database at least 3 years before and after such drug initiation. We assessed the prevalence of use of antihypertensive, antidiabetic, and lipid-lowering drugs within a 6-month period before and after orlistat initiation. Slopes and changes in slopes between these two periods were calculated using logistic generalized estimating equations and odds ratios (OR) with 95% confidence intervals (CI) are presented. RESULTS: A total of 6139 subjects had a prescription of orlistat between January 1992 and May 2009. Mean +/- SD age was 46.5 +/- 12.5 years, with a majority of female (88.7%). Use of antihypertensive, antidiabetic, and lipid-lowering drugs increased over time, but after start of orlistat the slopes levelled-off.Initiation of orlistat resulted in a significant change in slope for antihypertensive (OR 0.79; 95% CI 0.77-0.81), antidiabetic (0.86; 0.83-0.90), and lipid-lowering drugs (0.84; 0.81-0.88). CONCLUSIONS: Our data suggest a potential cost-effectiveness oforlistat, with a reduction in any cardiovascular comedication use over time. By potentially reducing costs of other medications use, orlistat remains as a unique option for tackling the obesity epidemic.