Orlistat, an inhibitor of intestinal lipase, has been available for the treatment of obesity for nearly two decades. In conjunction with a hypocaloric diet, orlistat treatment results in a placebo-subtracted reduction in body weight of around 3 kg at 1 year, and increases the likelihood of achieving clinically significant (≥5%) weight loss by around 20%. Orlistat-induced weight loss also confers modest improvements in systolic and diastolic blood pressure, low-density lipoprotein (LDL) cholesterol, glycemic parameters, and progression to diabetes in people with impaired glucose tolerance. Overall, it has a good safety profile, and serious adverse events (including reports of severe kidney and liver injury) are rare. However, a high rate of gastrointestinal side effects limits adherence to treatment.