The efficacy and safety of SGLT2 inhibitors combined with ACEI/ARBs in the treatment of type 2 diabetes mellitus: A meta-analysis of randomized controlled studies

ABSTRACT

Background

The efficacy and safety of the combination therapy with sodium–glucose cotransporter 2 (SGLT2) inhibitors and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBs) in the treatment of type 2 diabetes mellitus (T2DM) was not clear yet.

Research design and methods

A meta-analysis of randomized controlled studies (RCTs) was performed by searching in CENTRAL, Web of Science, PubMed, and Embase.

Results

Eight RCTs involving 6,386 participants were finally enrolled in this meta-analysis. Compared with placebo plus ACEI/ARBs, combined therapy with SGLT2 inhibitors and ACEI/ARBs induced a significant reduction in glycated hemoglobin (HbA1c) level by 0.43% (95% confidence interval [CI]: −0.55, −0.31), fasting plasma glucose level by 16.51 mg/dL (95% CI: −21.94, −11.08); systolic/diastolic blood pressure (BP) by 5.34 mmHg (95% CI: −7.47, −3.21)/1.27 mmHg (95% CI: −1.95, −0.59), respectively; and body weight (BW) by 1.45 kg (95% CI: −2.24, −0.65). Combined therapy was also found to be associated with a lower risk of adverse events. However, a higher risk of genital infections was observed with combination therapy than with placebo.

Conclusions

This combination therapy showed satisfactory effects on lowering glycemic, BW, and BP in the treatment of T2DM patients. The safety of this combination therapy was also acceptable.

KEYWORDS:

• Sodium-glucose cotransporter 2 inhibitors
• angiotensin-converting enzyme inhibitors
• angiotensin receptor blockers
• combination therapy
• type 2 diabetes mellitus

Author contributions

Yuwen Cai made a significant contribution to the study design, execution, acquisition, analysis, and interpretation of data. Weinan Shi and Gaosi Xu made significant contribution to the conception of this study. All authors agreed to take responsibility and be accountable for the contents of the article and to share responsibility to resolve any questions raised about the accuracy or integrity of the published work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received honoraria or lecture fees from all manufacturers of SGLT-2 inhibitors. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.