Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (K_ATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively manages post-meal glucose spikes when taken right before meals. Hypoglycemia risk increases if meals are delayed, skipped, or low in carbohydrates. Suitable for elderly patients and those with severe sulfur or sulfonylurea allergies, it can be used alone or combined with biguanides.

Repaglinide is absorbed rapidly, reaching peak blood levels within an hour, making it suitable for pre-meal usage. It's mainly metabolized by the liver, with a small amount processed by the kidneys, necessitating caution in patients with renal insufficiency. Its major side effect is hypoglycemia, and its effectiveness can decline after initial improvements. Some drugs may enhance its action by altering its metabolism or displacing it from plasma protein-binding sites.

Nateglinide promotes insulin secretion swiftly but less enduringly than other oral antidiabetic agents. It effectively reduces post-meal glycemic spikes when taken shortly before meals. Metabolized primarily by hepatic CYPs, it should be used cautiously in patients with liver insufficiency. Certain drugs may reduce the glucose-lowering effect of nateglinide or increase the risk of hypoglycemia. Unlike other insulin secretagogues, nateglinide may lead to fewer hypoglycemic episodes but has similar secondary failure rates.