Dose-dependent effects of SGLT2 inhibitors on circadian blood pressure in hypertensive patients with diabetes: A systematic review and Bayesian network meta-analysis

Objective The impact of dose variation of Sodium-glucose co-transporter 2 (SGLT2) inhibitors in reducing blood pressure (BP) in patients with diabetes and hypertension remains unclear. Methods A systematic search up to December 29, 2024 identified randomized trials reporting SGLT2 inhibitor effects on 24-h, daytime, nighttime, and office BP, along with hypoglycemia, urinary tract infections, and volume depletion. Continuous outcomes were synthesized as mean differences and safety outcomes as odds ratios within a Bayesian random-effects network meta-analysis. Dose–response patterns were examined using Bayesian meta-regression (ΔDIC), and treatment rankings were derived using SUCRA. Results Nine RCTs involving 9093 participants were included. SGLT2 inhibitors produced modest reductions across 24-h, daytime, nighttime, and office BP, with the largest numerical effect for empagliflozin 25 mg (SBP –5.93 mm Hg), but no credibly significant differences among agents in head-to-head comparisons. Safety outcomes showed no credibly significant excess risk for hypoglycemia, UTI, or volume depletion, with overall event rates low. Bayesian meta-regression yielded ΔDIC values near zero, indicating no detectable dose–response pattern for either blood pressure or safety outcomes. Conclusion SGLT2 inhibitors produced modest and consistent reductions in BP, with no evidence of dose-dependence or meaningful differences among agents. Safety events were not credibly increased. These findings support their use as adjunctive therapy in patients with diabetes and hypertension.