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.