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

Expert Opin Drug Saf. 2020 Nov;19(11):1497-1504. doi: 10.1080/14740338.2020.1817378. Epub 2020 Sep 3.

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 receptor blockers; angiotensin-converting enzyme inhibitors; combination therapy; type 2 diabetes mellitus.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Angiotensin Receptor Antagonists / administration & dosage*
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Glycated Hemoglobin / drug effects
  • Humans
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage*
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Blood Glucose
  • Glycated Hemoglobin A
  • Sodium-Glucose Transporter 2 Inhibitors
  • hemoglobin A1c protein, human