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

Davood Semirani-Nezhad; Khatere Roozbehi; Arman Soltani Moghadam; Elham Ebrahimi; Keyvan Salehi; Anahita Hashempoor; Sima Shamshiri; Tara Azardar; Mahshad Sabri; Ali Moradi; Kaveh Hosseini; Mani Khorsand Askari; Toshiki Kuno; Fatemeh Chichagi

doi:10.1016/j.ijcrp.2025.200569

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

Int J Cardiol Cardiovasc Risk Prev. 2026 Jan 5:29:200569. doi: 10.1016/j.ijcrp.2025.200569. eCollection 2026 Jun.

Authors

Davood Semirani-Nezhad^{1

2}, Khatere Roozbehi^{1

2}, Arman Soltani Moghadam^{1

2}, Elham Ebrahimi^{1

2}, Keyvan Salehi^{1

2}, Anahita Hashempoor³, Sima Shamshiri^{1

2}, Tara Azardar⁴, Mahshad Sabri^{1

2}, Ali Moradi⁵, Kaveh Hosseini^{1

6

7}, Mani Khorsand Askari⁸, Toshiki Kuno⁹, Fatemeh Chichagi^{1

2}

Affiliations

¹ Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
² Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
³ Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴ Tehran University of Medical Sciences, Tehran, Iran.
⁵ Internal Medicine, Blake Hospital, HCA Healthcare, University of South Florida, Morsani College of Medicine, Bradenton, FL, USA.
⁶ Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.
⁷ Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
⁸ University of Toledo Medical Center, Toledo, OH, USA.
⁹ Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

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.

Keywords: Blood pressure; Diabetes mellitus; Hypertension; SGLT2 inhibitors.

Publication types

Review