A 48-year-old man with type 2 diabetes has an HbA1c of 7.8% on metformin monotherapy. The physician adds sitagliptin. The mechanism by which DPP-4 inhibitors lower blood glucose is:
- A Inhibition of degradation of endogenous incretin hormones GLP-1 and GIP ✓
- B Direct stimulation of insulin secretion from pancreatic beta cells
- C Increasing glucose uptake in skeletal muscle via AMPK activation
- D Inhibition of renal glucose reabsorption in the proximal tubule
Correct answer: A. Inhibition of degradation of endogenous incretin hormones GLP-1 and GIP
Explanation
DPP-4 inhibitors block the enzyme that degrades incretin hormones GLP-1 and GIP, thereby prolonging their activity and enhancing glucose-dependent insulin secretion. They do not directly stimulate beta cells. AMPK activation is the mechanism of metformin. SGLT2 inhibition blocks renal glucose reabsorption.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
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