Therapeutics and Drugs Briefs

Orlistat for Weight Loss and Prevention of Weight Regain

Source: Sjostrom L, et al. Lancet 1998;352:167-173.

Obesity is a major personal and public health problem throughout the world. After two decades of a relative pharmacotherapeutic vacuum, recently employed agents have been causally implicated in cardiovascular pathology. A new agent that would be efficacious without causing, in particular, serious cardiovascular sequelae would be very welcome.

Orlistat inhibits gastrointestinal lipases, hence reducing absorption of dietary fat. On a typical regimen of orlistat 120 mg tid, a reduction of about 30% fat absorption could be anticipated. The current study enrolled men and women of BMI at least 28 for a double-blind, randomized, placebo-controlled parallel-group study (n = 688). In the first year of the study, patients were assigned to a hypocaloric diet (600 kcal/d deficit). In the second year, patients were placed on a eucaloric (weight maintenance) diet. Active treatment was 120 mg orlistat tid.

At the end of the first year, the active treatment group had lost about nine pounds more than the placebo group. In the second year, patients maintained on orlistat regained only half as much weight as placebo recipients. Surrogate end points such as total cholesterol, LDL, serum glucose, and insulin were more favorably affected by orlistat than placebo. Attesting to the overall tolerability of orlistat, in the first year of therapy, premature withdrawal was almost 30% more common in the placebo group. Gastrointestinal side effects were more common with active treatment. Orlistat may offer an attractive alternative for long-term palliation of obesity.