Question

All of the following antidiabetic drugs act by enhancing insulin secretion except

• A. Exenatide
• B. Sitagliptin
• C. Rosiglitazone
• D. Repaglinide

Hint:

Thiazolidinediones (TZDs like Rosiglitazone and Pioglitazone) and Biguanides (like Metformin) are classic "insulin sensitizers" that do not cause hypoglycemia because they do not stimulate insulin secretion.

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Antidiabetic drugs can be categorized as those that stimulate insulin release from pancreatic beta-cells (secretagogues and incretin-based therapies) and those that improve peripheral insulin sensitivity or decrease glucose absorption (sensitizers).
Detailed Explanation:
Let us review the mechanism of action of each listed drug:
- Exenatide: This is a glucagon-like peptide-1 (GLP-1) receptor agonist.
It binds to GLP-1 receptors on pancreatic beta-cells, stimulating glucose-dependent insulin secretion.
- Sitagliptin: This is a dipeptidyl peptidase-4 (DPP-4) inhibitor.
By preventing the degradation of endogenous incretins (GLP-1 and GIP), it increases their levels, which in turn enhances insulin secretion.
- Repaglinide: This is a meglitinide analog that acts as an insulin secretagogue.
It binds to ATP-dependent $K^+$ channels on beta-cells, causing membrane depolarization, calcium influx, and subsequent insulin exocytosis.
- Rosiglitazone: This is a thiazolidinedione (TZD).
It acts as a selective agonist for the peroxisome proliferator-activated receptor-gamma (PPAR-$\gamma$), a nuclear receptor.
It enhances insulin sensitivity in peripheral tissues (adipose tissue, skeletal muscle, and liver) and reduces hepatic glucose output.
It does not stimulate or enhance insulin secretion from the pancreas.

Step 2: Final Answer:
Rosiglitazone acts as an insulin sensitizer and does not enhance insulin secretion.