metformin + orlistat

Metformin + orlistat is a combination therapy involving two oral small molecule drugs, metformin and orlistat, used primarily for the treatment of obesity and weight management, particularly in patients with type 2 diabetes or prediabetes. Metformin is an insulin-sensitizing agent that decreases hepatic glucose production and improves peripheral insulin sensitivity. Orlistat is a pancreatic and gastric lipase inhibitor that reduces dietary fat absorption by inhibiting the breakdown of triglycerides in the intestine. The rationale for combining these agents lies in their complementary mechanisms—metformin targets glucose metabolism while orlistat targets fat absorption. Clinical studies have shown both drugs are effective individually for weight loss; however, evidence suggests that their combination does not provide significant additional benefit over monotherapy with either drug alone regarding weight loss or improvement in insulin resistance[1][6][9]. The combination may be considered when both glycemic control and weight reduction are desired, but tolerability (notably gastrointestinal side effects) can be a concern[10].