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Verapamil decreases the glucose‐lowering effect of metformin in healthy volunteers
Author(s) -
Cho Sung Kweon,
Kim Choon Ok,
Park Eun Seok,
Chung JaeYong
Publication year - 2014
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12476
Subject(s) - verapamil , metformin , medicine , pharmacology , endocrinology , cardiology , diabetes mellitus , calcium
Aim The organic cation transporter 1 ( OCT1 ) plays a key role in the cellular transport of metformin and its subsequent glucose‐lowering effect. A recent non‐clinical study reported that metformin uptake into hepatocytes is regulated via OCT1 , and that uptake was strongly inhibited by verapamil. Therefore, we investigated the effects of verapamil co‐administration on the pharmacokinetics and pharmacodynamics of metformin in humans. Methods We evaluated the pharmacokinetics and the anti‐hyperglycaemic effects of metformin using an oral glucose tolerance test ( OGTT ) in 12 healthy participants, before (day 1) and after metformin treatment (day 2), and again on days 15 and 16 after co‐administration with verapamil. Results Verapamil inhibited the ability of metformin to reduce maximum blood glucose concentrations (Δ G max ) by 62.5% ( P = 0.008) and decreased the area under the glucose concentration–time curve (Δ AUC gluc ) by 238% ( P = 0.015). However, verapamil did not significantly alter the C max and the AUC of metformin, nor its renal clearance. Conclusions Our results suggest that verapamil remarkably decreases the glucose‐lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1 .