What is the primary mechanism of action of DPP-4 inhibitors?

• A. Promotes glycemic control by enhancing incretin hormones (stimulates glucose-dependent insulin release, suppresses glucagon release)
• B. Directly increases insulin sensitivity
• C. Inhibits glucagon receptor signaling
• D. Increases hepatic glucose production

Answer: (D)

DPP-4 inhibitors work by preserving incretin hormones, mainly GLP-1 and GIP, by blocking the enzyme that breaks them down. Incretins are gut-derived hormones released after a meal that amplify insulin release from the pancreas in a glucose-dependent manner and suppress glucagon release from alpha cells. This combination helps lower postprandial and overall blood glucose while reducing the risk of hypoglycemia, because the insulin response is tied to the glucose level rather than happening all the time.

So the primary action is to enhance incretin signaling, which leads to more glucose-dependent insulin secretion and less glucagon—helping control glucose without driving hepatic glucose production up. The other options don’t fit this mechanism: increasing insulin sensitivity is more typical of other drug classes, directly inhibiting glucagon receptors isn’t how DPP-4 inhibitors work, and increasing hepatic glucose production would worsen hyperglycemia rather than improve it.