Sulfonylureas and Meglitinides are oral hypoglycemic drugs directly stimulate release of insulin from pancreatic beta cells. Meglitinides act on the same β-cell receptor as sulphonylureas, but have a different chemical structure with a few major differences.

For example, meglitinides bind to the sulfonylurea receptor in beta cells (the insulin-producing cells of the pancreas), but at a different part of the receptor than the sulfonylureas do. The interaction of the meglitinides with the receptor is not as “tight” as that of the sulfonylureas, translating to a much shorter duration of action and a higher blood glucose level needed before the drugs produce insulin secretion from the pancreas. So, Meglitinides need to be taken more often than sulfonylureas because they work for a shorter amount of time.

In head-to-head comparisons with sulfonylureas, metiglinides failed to demonstrate better glucose control and led to a similar number of hypoglycaemic events. No significant differences were observed in terms of lipid profile and body weight reduction.

Meglitinides may be used in individuals allergic to sulfonylureas and in older adults unable to take insulin when the goal is to avoid hypoglycemia (McCulloch, 2015). Another advantage of meglitinides is their flexibility compared with sulfonylureas because of their faster onset and shorter duration of action (Pfeiffer & Klein, 2014).

The cost of meglitinides is relatively high. Similar to sulfonylureas, meglitinides lose their effectiveness as beta cell function declines over time (Marino, 2014). These agents are metabolized by the liver and, therefore, should be avoided in workers with liver dysfunction and used cautiously if renal dysfunction is present (Novartis, 2013; Novo Nordisk, 2011) although repaglinide has little renal clearance (McCulloch, 2015). 

Sulfonylureas are usually taken once or twice a day, in the morning and/or evening, depending on the brand:

  • Chlorpropramide is taken once a day (typical daily dose: 100 mg to 500 mg)
  • Glipizide is taken once or twice a day (typical daily dose: 5 mg to 40 mg)
  • Glyburide is taken once or twice a day (typical daily dose: 1.25 mg to 20 mg)
  • Glimepiride is taken once a day (typical dose: 1 mg to 4 mg; maximum 8 mg daily)

Meglitinides are usually taken 15-30 minutes before each meal:

  • Repaglinide is taken at doses ranging usally from 0.5 mg to 4 mg with each meal
  • Nateglinide is taken at doses ranging usually from 60 mg to 120 mg