ArticlePharmaceutics2020
Pharmacokinetic Interaction between Metformin and Verapamil in Rats: Inhibition of the OCT2-Mediated Renal Excretion of Metformin by Verapamil.
Article in Pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Effect of Verapamil on Blood Glucose in Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.Cardiovascular drugs and therapy · 2026Pooled it
- Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions.Journal of translational medicine · 2025Review
- Effect of Cimetidine on Metformin Pharmacokinetics and Endogenous Metabolite Levels in Rats.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract.Frontiers in pharmacology · 2023Article
- Article
- Examination of Urinary Excretion of Unchanged Drug in Humans and Preclinical Animal Models: Increasing the Predictability of Poor Metabolism in Humans.Pharmaceutical research · 2021Review
- Evaluating the antidiabetic effects of R-verapamil in type 1 and type 2 diabetes mellitus mouse models.PloS one · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The incidence of hypertension in diabetic patients has been increasing and contributing to the high mortality of diabetic patients. Recently, verapamil use was found to lower fasting blood glucose levels in diabetic patients, which led to a new indication of verapamil as combination treatment with anti-diabetic agents such as metformin. As pharmacokinetic (PK) interaction can affect drug efficacy and safety in drug combination, their PK-based interaction is recommended to be evaluated in preclinical levels as well as clinical levels. In case of metformin and verapamil, organic cation transporter (OCT) 1 and 2 primarily mediate metformin distribution to the liver and its elimination into urine, whereas cytochrome P450 is responsible for the hepatic metabolism of verapamil. Verapamil is also known as a potential OCT2 inhibitor. Thus, PK interaction between metformin (30 mg/kg) and verapamil (20 mg/kg) were investigated after their simultaneous administration to rats. In our results, verapamil inhibited the OCT2-mediated renal excretion of metformin, subsequently leading to increase of the systemic exposure of metformin. In contrast, metformin did not influence the pharmacokinetic pattern of verapamil. Although the further clinical investigation is required, our finding suggests a possibility of OCT2-mediated interaction of metformin and verapamil.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.