Meglitinide analogues:: a review of clinical data focused on recent trials

Glinides represent a chemically heterogeneous new class of insulin-secreting agents characterized by a rapid onset and short duration of action. They act by closure of the ATP-dependant K channel. Repaglinide, the only glinide available in France, has an equivalent HbA(1c) lowering effect to conventional sulfonylureas but reduces predominantly postprandial glucose levels. Several studies indicate a decreased risk of hypoglycaemias, particularly nocturnal or in case of a shift or omission of a meal. This drug appears particularly useful in early stage type 2 diabetes or in combination with metformin. The only significant drug-drug interaction concerns gemfibrozil. Due to its hepatic metabolism and biliary elimination, repaglinide can be used in patients with renal insufficiency. Nateglinide has a even shorter duration of action and has almost no effect on fasting plasma glucose levels. For this reason, this drug is only indicated in combination with metformin in the countries where it is licensed. Several experimental data suggest that glinides could preserve beta cell function over time better than hypoglycaemic sulfonylureas, and that the improvement of post-prandial glucose levels could exert a long term protective cardiovascular effect.