American Board of Internal Medicine (ABIM) Certification Practice Exam

What is the mechanism by which DPP-4 inhibitors enhance endogenous GLP-1?

1. They act directly on the GLP-1 receptor

2. They increase the half-life of endogenous GLP-1

3. They inhibit glucagon secretion

4. They stimulate insulin secretion directly

The correct answer is: They increase the half-life of endogenous GLP-1

DPP-4 inhibitors enhance endogenous GLP-1 primarily by increasing the half-life of this incretin hormone. Dipeptidyl peptidase-4 (DPP-4) is an enzyme that rapidly degrades GLP-1 following its release from the intestines after food intake. By inhibiting DPP-4, these inhibitors prevent the breakdown of GLP-1, allowing it to persist in the bloodstream for a longer duration. This prolonged half-life enhances the physiological effects of GLP-1, which include increasing insulin secretion in response to meals, reducing glucagon levels, and slowing gastric emptying, ultimately contributing to improved glycemic control in patients with type 2 diabetes. The other options propose mechanisms that do not align with how DPP-4 inhibitors function. They do not act directly on the GLP-1 receptor but instead modulate the availability of GLP-1 itself. While they might indirectly influence glucagon secretion or insulin secretion through the actions of GLP-1, the primary mechanism is tied to the increase in GLP-1's half-life rather than directly stimulating insulin secretion or inhibiting glucagon secretion.