Effect of Sodium-Glucose Cotransport-2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of 43 Randomized Control Trials With 22 528 Patients

Mohsen Mazidi, Peyman Rezaie, Hong-Kai Gao, Andre Pascal Kengne, Mohsen Mazidi, Peyman Rezaie, Hong-Kai Gao, Andre Pascal Kengne

Abstract

Background: The sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of oral hypoglycemic agents. We undertake a systematic review and meta-analysis of prospective studies to determine the effect of SGLT2 on blood pressure (BP) among individuals with type 2 diabetes mellitus.

Methods and results: PubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched to identify trial registries evaluating the impact of SGLT2 on BP. Random-effects models meta-analysis was used for quantitative data synthesis. The meta-analysis indicated a significant reduction in systolic BP following treatment with SGLT2 (weighted mean difference -2.46 mm Hg [95% CI -2.86 to -2.06]). The weighted mean differences for the effect on diastolic BP was -1.46 mm Hg (95% CI -1.82 to -1.09). In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were -2.08 mg/dL (95% CI -2.51 to -1.64) and 0.77 mg/dL (95% CI 0.33-1.21), respectively. The weighted mean differences for the effect of SGLT2 on body weight was -1.88 kg (95% CI -2.11 to -1.66) across all studies. These findings were robust in sensitivity analyses.

Conclusions: Treatment with SGLT2 glucose cotransporter inhibitors therefore has beneficial off-target effects on BP in patients with type 2 diabetes mellitus and may also be of value in improving other cardiometabolic parameters including lipid profile and body weight in addition to their expected effects on glycemic control. However, our findings should be interpreted with consideration for the moderate statistical heterogeneity across the included studies.

Keywords: Sodium‐glucose cotransport‐2 inhibitors; blood pressure; diabetes mellitus; meta‐analysis.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
PRISMA flow chart for study selection.
Figure 2
Figure 2
Plot to display weighted mean differences (bars) and 95% CIs (whiskers) for the impact of SGLT2 therapy on systolic blood pressure. SGLT 2, sodium‐glucose cotransporter 2.
Figure 3
Figure 3
Plot to display weighted mean differences (bars) and 95% CIs (whiskers) for the impact of SGLT2 inhibitor therapy on diastolic blood pressure. SGLT 2, sodium‐glucose cotransporter 2.
Figure 4
Figure 4
Funnel plots for publication bias in the studies selected for the analysis of the effects of SGLT2 inhibitors on systolic blood pressure. Open circles represent observed published studies; open diamond represents the observed effect size. SGLT 2, sodium‐glucose cotransporter 2.
Figure 5
Figure 5
Trim‐and‐fill method (systolic blood pressure) to impute potentially missing studies. No potentially missing study was imputed in funnel plot. Open circles represent observed published studies; open diamond represents the observed effect size; closed diamond represents imputed effect size.
Figure 6
Figure 6
Funnel plots for publication bias in the studies selected for the analysis of the effects of SGLT2 inhibitors on diastolic blood pressure. Open circles represent observed published studies; open diamond represents the observed effect size. SGLT 2, sodium‐glucose cotransporter 2.
Figure 7
Figure 7
Trim‐and‐fill method (diastolic blood pressure) to impute potentially missing studies. One potentially missing study was imputed in funnel plot. Open circles represent observed published studies; open diamond represents observed effect size; closed diamond represents imputed effect size; closed circle represent imputed study.

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