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Sodium-glucose co-transporter-2 inhibitors and all-cause mortality: A meta-analysis of randomized controlled trials

Giovanni Antonio Silverii1, Matteo Monami2, Edoardo Mannucci1

  • 1Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy.

Diabetes, Obesity & Metabolism
|December 7, 2020
PubMed

Insights

Sodium-glucose co-transporter-2 (SGLT2) inhibitors significantly reduce all-cause mortality in patients. This meta-analysis of randomized trials found consistent benefits across different SGLT2 inhibitor molecules and trials.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Cardiovascular disease remains a leading cause of mortality globally.
  • Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a class of drugs primarily used for type 2 diabetes management.
  • Emerging evidence suggests potential benefits beyond glycemic control.

Purpose of the Study:

  • To conduct a meta-analysis assessing the impact of SGLT2 inhibitors on all-cause mortality.
  • To investigate potential differences in efficacy across various SGLT2 inhibitor drugs and clinical trials.

Main Methods:

  • Systematic review and meta-analysis of randomized clinical trials (RCTs).
  • Inclusion criteria: RCTs >52 weeks, ≥100 patients/arm, comparing SGLT2 inhibitors vs. placebo/comparator.
  • Data synthesis included mortality events and subgroup analyses.

Main Results:

  • 21 RCTs with 39,593 patients in SGLT2 inhibitor arms and 30,771 in comparator arms were analyzed.
  • A significant reduction in all-cause mortality was observed with SGLT2 inhibitors (MH-OR [95% CI] 0.86 [0.81, 0.91], P < .00001).
  • Meta-regression indicated treatment effect was directly associated with the proportion of Asian subjects and inversely with Caucasian patients.

Conclusions:

  • SGLT2 inhibitors demonstrate a significant benefit in reducing all-cause mortality in the analyzed RCTs.
  • The observed mortality benefit appears consistent across different SGLT2 inhibitor molecules.
  • Patient ethnicity may influence the treatment effect of SGLT2 inhibitors on mortality.
Keywords:
SGLT2 inhibitorscanagliflozindapagliflozinempagliflozinertugliflozinmeta-analysis

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