Verapamil decreases the glucose‐lowering effect of metformin in healthy volunteers

• Published in: British journal of clinical pharmacology 2014-12, Vol.78 (6), p.1426-1432
• Main Authors: Cho, Sung Kweon, Kim, Choon Ok, Park, Eun Seok, Chung, Jae‐Yong
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - analysis; drug interaction; Drug Interactions; Humans; Hypoglycemic Agents - pharmacology; Male; metformin; Metformin - pharmacokinetics; Metformin - pharmacology; OCT1; Organic Cation Transport Proteins - antagonists & inhibitors; Organic Cation Transporter 1 - antagonists & inhibitors; verapamil; Verapamil - pharmacology
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.12476

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.