Verapamil decreases the glucose‐lowering effect of metformin in healthy volunteers
British journal of clinical pharmacology, 2014•Wiley Online Library
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 …
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 …
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 (ΔGmax) by 62.5% (P = 0.008) and decreased the area under the glucose concentration–time curve (ΔAUCgluc) by 238% (P = 0.015). However, verapamil did not significantly alter the Cmax 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.
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