Repaglinide is believed to work by

• A. decreasing hepatic gluconeogenesis
• B. stimulating the release of insulin from the pancreas
• C. increasing hepatic gluconeogenesis
• D. reducing glucagon secretion from the pancreas

Answer: (B)

Repaglinide is an insulin secretagogue, meaning its main action is to make the pancreas release insulin. It does this by binding to receptors on pancreatic beta cells and closing ATP-sensitive potassium channels, which depolarizes the cell. The depolarization opens voltage-gated calcium channels, causing insulin-containing granules to fuse with the cell membrane and release insulin. This rise in insulin helps lower blood glucose after meals when glucose levels rise, explaining why repaglinide is taken before meals to blunt postprandial spikes. It does not primarily reduce hepatic glucose production like metformin, nor does it directly increase hepatic glucose output or suppress glucagon secretion; its principal effect is boosting endogenous insulin secretion. This mechanism also means there’s a risk of hypoglycemia if meals are missed or not eaten adequately.