A 52-year-old man with type 2 diabetes on glimepiride 4 mg daily complains of 6 kg weight gain over 4 months without any change in diet. His fasting glucose is well controlled. The weight gain associated with sulfonylureas is primarily mediated by which mechanism?

• A Increased lipogenesis via PPAR-gamma activation in adipose tissue
• B Stimulation of appetite centers in the hypothalamus via AMPK activation
• C Elevated insulin levels promoting anabolic fat storage and reducing glycosuria ✓
• D Fluid retention secondary to increased aldosterone secretion

Explanation

Sulfonylureas stimulate insulin secretion, which promotes anabolic fat storage and reduces glucose loss in urine, leading to weight gain. PPAR-gamma activation (A) is the mechanism of thiazolidinediones. Sulfonylureas do not act centrally on appetite (B) and do not cause fluid retention via aldosterone (D).

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.