Drug Interactions Newsletter

Volume 2, Issue 26, 07/06/2010

Question

What is the mechanism of action by which gemfibrozil (Lopid) increases the blood levels of repaglinide (Prandin) 8-fold?

Answer

Patients with type 2 diabetes mellitus can be managed by a number of different medications which include both oral and parenteral dosage formulations.  The oral drug therapy options include a class of medications called the meglitinides, of which repaglinide (Prandin) is a member.  Repaglinide is a short acting medication that works by stimulating the beta-islet cells to secrete insulin.  Unfortunately, many patients do not receive adequate glucose control from many of the oral diabetic medications which can result in an unfavorable lipid profile or what is commonly called "diabetic dyslipidemia". Of the components in the lipid profile, the triglycerides levels are commonly increased.  In many cases, treating the abnormal glucose levels alone can improve the triglycerides as well as other parameters of the lipid profile.  However many patients will be unable to get their glucose and/or lipid profiles under control simply with oral antidiabetic therapy.  As such, patients are started on a fibric acid derivative such as gemfibrozil (Lopid) to gain additional control of the triglycerides. Therefore, it is plausible that patients with type 2 diabetes mellitus could be prescribed the combination of repaglinide and gemfibrozil at some point in the management of the disorders.

The issue for clinicians to take into consideration is the known 8-fold increase in the area under the curve (AUC) for repaglinide plasma concentrations with the coadministration of gemfibrozil.(1) This drug interaction also prolongs the half-life...

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