Orlistat MOA?

• A. Pancreatic lipase inhibitor
• B. Inhibits HMG-CoA reductase
• C. Inhibits intestinal cholesterol absorption
• D. PCSK9 inhibition

Answer: (A)

Orlistat works by blocking pancreatic lipase in the intestinal lumen, which prevents the digestion of dietary triglycerides into absorbable fatty acids and monoglycerides. With lipase inhibited, fats are not absorbed and are instead excreted, lowering the calories obtained from fat. This action stays largely in the gut, so systemic effects are minimal, but it can lead to steatorrhea and other fat-soluble vitamin absorption issues with long-term use. The other mechanisms belong to different drugs: blocking HMG-CoA reductase is how statins reduce hepatic cholesterol synthesis; inhibiting intestinal cholesterol absorption is how agents like ezetimibe work; and PCSK9 inhibitors enhance LDL receptor recycling to lower LDL cholesterol. Therefore, pancreatic lipase inhibition is the mechanism that best explains orlistat’s effect.