Dihydropyridine calcium-channel-blocker use in type 2 diabetes on RAS and SGLT2 inhibitors was associated with higher risk of major adverse kidney events (HR 1.33; 95% CI 1.03-1.73; P=0.03).
Cohort (n=31,031)
Does dihydropyridine calcium channel blocker therapy increase the risk of major adverse kidney events in adults with type 2 diabetes treated with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors?
In patients with type 2 diabetes treated with RAS inhibitors and SGLT2 inhibitors, the addition of dihydropyridine calcium channel blockers is associated with a higher risk of adverse kidney outcomes compared to other antihypertensive regimens.
Effect estimate: HR 1.33 (95% CI 1.03-1.73)
p-value: p=0.03
Rationale 40% eGFR decline or progression to kidney failure).Secondary outcomes included initiation of renal replacement therapy and all-cause mortality; Safety outcomes included hospitalizations and acute kidney injury.Analytical Approach: Inverse probability of treatment weighting was applied to balance baseline characteristics.Results: We included 31,031 patients with type 2 diabetes treated with both sodium-glucose cotransporter-2 inhibitors and renin-angiotensin inhibitors 12,172 (60.8%) received dihydropyridine calcium-channel-blockers, and 18,859 (39.2 %) received dihydropyridine J o u r n a l P r e -p r o o f calcium-channel-blockers -free therapy.Median follow-up was 1,260 days.Overall, 482 patients experienced major adverse kidney event, and 2064 patients died.dihydropyridine calciumchannel-blockers use was associated with a higher risk of major adverse kidney event compared with dihydropyridine calcium-channel-blocker-free therapy (weighted HR 1.33 95%CI 1.03-1.73,P=0.03), which remained significant after accounting for competing risk of death (HR 1.39, 95%CI 1.13-1.7,P=0.002).dihydropyridine calcium-channel-blocker use was not significantly associated with all-cause mortality or safety outcomes. Limitations:The observational design is subject to residual confounding and did not allow for full characterization of medication exposure. Conclusions:In patients with type 2 diabetes treated with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, concomitant therapy with dihydropyridine calcium channel blockers was associated with a higher risk of adverse kidney outcomes.These findings may help inform clinicians when weighing the potential risks and benefits of secondline antihypertensive therapy in this population.
Agur et al. (2026) conducted a cohort in Type 2 diabetes (n=31,031). Dihydropyridine calcium-channel-blockers vs. Dihydropyridine calcium-channel-blockers-free therapy was evaluated on Major adverse kidney event (MAKE; 40% eGFR decline or progression to kidney failure) (HR 1.33, 95% CI 1.03-1.73, p=0.03). Dihydropyridine calcium-channel-blocker use in type 2 diabetes on RAS and SGLT2 inhibitors was associated with higher risk of major adverse kidney events (HR 1.33; 95% CI 1.03-1.73; P=0.03).