Drug interactions with oral antidiabetic agents: pharmacokinetic mechanisms and clinical implications

Aleksi Tornio; Mikko Niemi; Pertti J Neuvonen; Janne T Backman

doi:10.1016/j.tips.2012.03.001

Drug interactions with oral antidiabetic agents: pharmacokinetic mechanisms and clinical implications

Trends Pharmacol Sci. 2012 Jun;33(6):312-22. doi: 10.1016/j.tips.2012.03.001. Epub 2012 Apr 2.

Authors

Aleksi Tornio¹, Mikko Niemi, Pertti J Neuvonen, Janne T Backman

Affiliation

¹ Department of Clinical Pharmacology, University of Helsinki and HUSLAB, Helsinki University Central Hospital, Tukholmankatu 8C, FIN-00290 Helsinki, Finland.

PMID: 22475684
DOI: 10.1016/j.tips.2012.03.001

Abstract

There is a growing epidemic of type 2 diabetes (T2DM), and it is associated with various comorbidities. Patients with T2DM are usually treated with multiple drugs, and are therefore at an increased risk of harmful drug-drug interactions (DDIs). Several potentially life-threatening DDIs concerning oral antidiabetic drugs have been identified. This has mostly been initiated by case reports but, more recently, the understanding of their mechanisms has greatly increased. In this article, we review the pharmacokinetic DDIs concerning oral antidiabetics, including metformin, sulfonylureas, meglitinide analogs, thiazolidinediones and dipeptidyl peptidase-4 inhibitors, and the underlying mechanistic basis that can help to predict and prevent DDIs. In particular, the roles of membrane transporters and cytochrome P450 (CYP) enzymes in these DDIs are discussed.

Publication types

Review

MeSH terms

Administration, Oral
Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
Benzamides / administration & dosage
Benzamides / pharmacokinetics
Cytochrome P-450 CYP2C8
Cytochrome P-450 CYP2C9
Cytochrome P-450 Enzyme Inhibitors*
Diabetes Mellitus, Type 2 / drug therapy*
Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
Drug Interactions
Humans
Hypoglycemia / complications*
Hypoglycemic Agents / administration & dosage
Hypoglycemic Agents / pharmacokinetics*
Metformin / administration & dosage
Metformin / pharmacokinetics
Sulfonylurea Compounds / administration & dosage
Sulfonylurea Compounds / pharmacokinetics
Thiazolidinediones / administration & dosage
Thiazolidinediones / pharmacokinetics

Substances

Benzamides
Cytochrome P-450 Enzyme Inhibitors
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Sulfonylurea Compounds
Thiazolidinediones
meglitinide
Metformin
CYP2C9 protein, human
Cytochrome P-450 CYP2C9
Aryl Hydrocarbon Hydroxylases
CYP2C8 protein, human
Cytochrome P-450 CYP2C8