Orlistat - Selective inhibition of caloric absorption can affect long-termbody weight

Orlistat is a novel, noncentrally acting antiobesity agent that selectively inhibits gastrointestinal lipase activity, thereby reducing the absorption of dietary fat by approximately one-third. In a series of 1- and 2-yr rand omized, placebo-controlled trials of obese subjects, treatment with orlista t in combination with a mildly calorie-restricted diet consistently produce d significantly greater mean weight loss than diet alone. More orlistat-tre ated subjects than placebo recipients achieved clinically meaningful weight reduction (greater than or equal to5% or greater than or equal to 10% of i nitial body weight) after 1 and 2 yr. Orlistat was also associated with a s ignificant reduction in the regain of lost weight during long-term treatmen t. In addition, orlistat therapy resulted in significant improvements in se veral cardiovascular risk factors including serum total and low-density lip oprotein-cholesterol, serum insulin levels, systolic and diastolic blood pr essure, and waist circumference. Furthermore, obese subjects with type 2 di abetes achieved a significantly greater decrease in body weight with orlist at compared with placebo, as well as significant improvements in HbA(1c) an d fasting glucose levels. Among subjects with impaired glucose tolerance, o rlistat compared with placebo reduced the proportion who developed type 2 d iabetes. Conversely, orlistat increased the proportion of subjects who achi eved a normalization of glucose tolerance. Orlistat acts locally in the gas trointestinal tract and is only minimally absorbed. In long-term clinical t rials, orlistat was well tolerated by both diabetic and nondiabetic subject s.