Efficacy and Safety of SGLT-2 Inhibitors in Patients with Uncontrolled or Resistant Hypertension: A Pilot Meta-Analysis of Randomized Clinical Trials.

Abstract

Introduction: Resistant or poorly controlled hypertension is a major contributor to cardiovascular morbidity and mortality despite contemporary multidrug regimens.

Aim: This study aimed to evaluate the efficacy and safety of SGLT-2 inhibitors as adjunctive agents to standard antihypertensive therapy in this high-risk population.

Methods: We systematically searched PubMed, Embase, Google Scholar, the Cochrane Library, ScienceDirect, and ClinicalTrials.gov for randomized controlled trials (RCTs) assessing SGLT-2 inhibitors in adults with poorly controlled hypertension (on ≥2 antihypertensive agents) or resistant hypertension. Primary outcome was the mean change in office systolic blood pressure (SBP). Mean differences (MDs) were pooled for continuous outcomes, and risk ratios (RRs) were pooled for dichotomous outcomes using random-effects models.

Results: Four RCTs (n=3,718) were included in the meta-analysis. SGLT-2 inhibitors significantly reduced office SBP in both the short term (MD -3.29 mmHg, 95% CI -3.96 to -2.62) and long term (MD -2.96 mmHg, 95% CI -3.58 to -2.35). The overall incidence of adverse events (pooled RR: 0.99, 95% CI 0.95 to 1.02), serious adverse events (pooled RR: 0.92, 95% CI 0.84 to 1.00), AKI (pooled RR: 0.98, 95% CI 0.80 to 1.21), and UTI (pooled RR: 0.88, 95% CI 0.36 to 2.17) were comparable between groups. However, SGLT-2 inhibitors were associated with a significantly increased risk of volume depletion, hypotension, and genital infections.

Conclusion: SGLT-2 inhibitors provide a modest incremental benefit in lowering office SBP for patients with uncontrolled or resistant hypertension on multidrug regimens with an overall acceptable safety profile. Future dedicated RCTs are warranted.