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Repaglinide and nateglinide ( meglitinides )

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Repaglinide and nateglinide are two of a class of orally active antidiabetic drugs, the meglitinides:

  • meglitinides are non-sulphonylurea beta-cell stimulators for the treatment of patients with type 2 diabetes - work by closing ATP-dependent potassium channels in the beta cell membrane
  • aim is to improve post-prandial insulin profiles - therefore can only be taken before meals and cannot be taken if meals are omitted
  • both have a licence for use as combination with metformin in patients with type 2 diabetes who are inadequately controlled by maximally tolerated doses of metformin alone; repaglinide also is licensed for use as a monotherapy in type 2 diabetes
  • nateglinide
    • novel amino acid derived from D-phenylamine
    • oral bioavailability about 70% - plasma concentrations generally peak in under 1 hour
    • following an oral dose of nateglinide - insulinotropic response to a meal occurs within 15 minutes and insulin concentrations return to baseline by about 2 hours
    • metabolised extensively by liver - elimination half-life about 1.5 hours
    • unwanted effects - mainly those of hypoglycaemia - sweating, tremor, weakness, dizziness; rare unwanted effects - hypersensitivity reactions such as rashes and itching and transient, mild elevations in liver enzymes that have rarely led to discontinuation of therapy (1)
  • repaglinide
    • derivative of carbamoylmethyl benzoic acid
    • oral bioavailability about 63% - plasma concentrations peak within 1 hour of administration
    • following an oral dose - insulinotropic response to a meal occurs within 30 minutes and insulin concentrations return to fasting levels within 4-6 hours
    • metabolised mainly by the liver - elimination half-life about 1 hour
    • unwanted effects are rare (less than 1 in 1,000 patients) and include hypoglycaemia, constipation, abdominal pain, diarrhoea, nausea, vomiting, visual disturbances, hypersensitivity reactions such as rashes and itching, and transient, mild elevations in liver enzymes that rarely lead to discontinuation of therapy (1)
  • Drug and Therapeutics bulletin review (1) concludes that "both repaglinide and nateglinide appear to lower postprandial glucose concentrations, but whether this effect is beneficial in terms of cardiovascular outcomes is unclear."

The summary of product characteristics must be consulted before prescribing either of these drugs.


  1. Drug and Therapeutics Bulletin (2003), 41 (7), 52-4.
  2. Drug and Therapeutics Bulletin (1999), 37 (11), 84-87

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