system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Blood Glucose, Drug Interactions, Humans, Hypoglycemic Agents, Male, Metformin, Organic Cation Transport Proteins, Organic Cation Transporter 1, Verapamil.
user
Does verapamil decrease the glucose-lowering effect of metformin in healthy volunteers? Context: 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. 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. 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.
assistant
Our results suggest that verapamil remarkably decreases the glucose-lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1. Final Decision: yes