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Drug Review: Meglitinides (repaglinide and nateglinide)

Meglitinides—also called glinides—increase the output of insulin by the pancreas beta cells into the bloodstream.  In that respect they are similar to sulfonylurea drugs, so the two classes are sometimes lumped together as insulin secretagogues.  If the pancreas produces no insulin at all—as in most cases of type 1 diabetes—these drugs won’t work. 

Two meglitinides are available in the U.S.: repaglinide is sold as Prandin, and nateglinide is Starlix. 

Meglitinides have about the same effectiveness as sulfonylureas, but are considerably more expensive.  Repaglinide and nateglinide  increase the pancreas’ output of insulin, working faster than sulfonylureas.  They don’t last as long as sulfonylureas, which may help avoid hypoglycemia.  Glinides work mostly to reduce sugar levels after meals.   

We don’t know if these drugs affect death rates. 


May be used alone or in combination with certain other diabetic drugs.  Since they have the same mechanism of action, sulfonylureas and meglitinides would not normally be used together.  In combination therapy, you want to use drug classes that work by different mechanisms. 


Starting dose for repaglinide is 0.5 mg by mouth before each meal.  Maximum dose is 4 mg before each meal.

Nateglinide: 120 mg by mouth immediately before each meal.

Side Effects

Hypoglycemia is the most common and potentially serious adverse effect of the meglitinides, but may be less common than with sulfonylureas.   

Weight gain is common. 

Precautions . . .

Nateglinide:  Use with great caution, if at all, in the setting of severe kidney disease and moderate to severe liver disease.

Repaglinide:  Use cautiously in severe kidney and liver disease.

Steve Parker, M.D.

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