Verapamil versus other calcium channel blockers and risk of incident type 2 diabetes mellitus: emerging evidence from a systematic review and meta-analysis

Verapamil has attracted interest as a potential means of preserving pancreatic β-cell function through suppression of thioredoxin-interacting protein (TXNIP), raising the question of whether it differs from other calcium channel blockers in the risk of incident type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis was conducted to quantify that association and assess the certainty of the evidence. PubMed, Embase, Scopus, the Cochrane Library, ClinicalTrials.gov and WHO ICTRP were searched from inception to 10 September 2026. Randomised trials and observational cohort studies comparing verapamil with another calcium channel blocker and reporting incident T2DM were eligible. Adjusted hazard ratios were pooled using a random-effects model with the Hartung-Knapp-Sidik-Jonkman method. Risk of bias was assessed using ROBINS-I and certainty of evidence using GRADE. Two population-based cohort studies were included, one from Taiwan and one from Australia. The pooled estimate favoured verapamil but was imprecise (HR 0.78, 95% CI 0.48-1.26), and was compatible with a substantial reduction in risk, with no difference, and with a modest increase. Statistical significance depended on the method used to account for between-study uncertainty, being present under the DerSimonian-Laird estimator (0.78, 95% CI 0.68-0.88) but not under the primary analysis. Both studies were at serious risk of bias from residual confounding, and the certainty of evidence was very low. The available evidence is insufficient to inform the choice of calcium channel blocker, and a randomised comparison with prespecified glycaemic ascertainment is required.