SGLT2 inhibitors and GLP1 agonists administered without metformin compared to other glucose-lowering drugs in patients with type 2 diabetes mellitus to prevent cardiovascular events: A systematic review

Diabet Med. 2021 Mar;38(3):e14502. doi: 10.1111/dme.14502. Epub 2021 Jan 4.

Abstract

Objectives: To assess the efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sodium-glucose co-transporter 2 (SGLT2) inhibitors, administered without metformin on cardiovascular outcomes in type 2 diabetes patients.

Methods: A systematic review was performed according to Cochrane's methodological standards. We included randomized clinical trials (RCTs) on adult type 2 diabetes patients, assessing the efficacy of SGLT2 inhibitors and GLP1-RAs compared to other glucose-lowering drugs and/or RCTs that presented data of a subgroup of type 2 diabetes patients without metformin use at baseline. The main outcome was the reduction of the risk of any major adverse cardiovascular events (MACE) reported individually or as a composite outcome.

Results: Five RCTs including 50,725 type 2 diabetes patients, of whom 10,013 had not received metformin, were included in this meta-analysis. Three of these studies assessed the efficacy of GLP1-RAs and two of SGLT2 inhibitors. In patients without metformin at baseline, GLP1-RAs in comparison with placebo reduced the risk of MACE significantly by 20% (HR: 0.80; 95% CI: 0.71-0.89). SGLT2 inhibitors also significantly reduced the risk of MACE by 32% (HR: 0.68; 95% CI: 0.57-0.81).

Conclusions: SGLT2 inhibitors and GLP1-RAs provided without metformin at baseline may reduce the risk of MACE in comparison with placebo in type 2 diabetes patients at increased risk of cardiovascular events.

Keywords: GLP1-RAs; SGLT2 inhibitors; cardiovascular; diabetes; meta-analysis.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Angiopathies / prevention & control
  • Drug Therapy, Combination
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / classification
  • Metformin / administration & dosage
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage*

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Metformin