AimThe 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 viaOCT1, 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.MethodsWe 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.ResultsVerapamil 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 theCmaxand theAUCof metformin, nor its renal clearance.ConclusionsOur results suggest that verapamil remarkably decreases the glucose‐lowering effect of metformin, possibly by acting as a competitive inhibitor ofOCT1.