Network meta-analysis of cardiovascular outcomes in randomized controlled trials of new antidiabetic drugs

Int J Cardiol. 2018 Mar 1;254:291-296. doi: 10.1016/j.ijcard.2017.12.039. Epub 2017 Dec 20.


Background: Randomized controlled trials (RCTs) directly comparing cardiovascular outcomes of new antidiabetic drugs are lacking. We used network meta-analysis to compare new antidiabetic drug classes with respect to major adverse cardiovascular events (MACE) and mortality.

Methods: We searched MEDLINE, EMBASE, the Cochrane database, and up to 30 December 2016 for RCTs involving SGLT-2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in diabetic patients that reported MACE and deaths. Outcomes were compared with frequentist and Bayesian methods using R statistics.

Results: Seven RCTs with altogether 62,268 patients were included in the network meta-analysis. The SGLT-2 inhibitor and GLP-1 RAs reduced MACE (OR 0.85, 95%CI 0.73-0.99 and 0.89, 0.82-0.97, respectively) and all-cause mortality (0.67, 0.55-0.81 and 0.89, 0.80-0.99, respectively) compared to placebo. Furthermore, the SGLT-2 inhibitor reduced all-cause mortality compared to GLP-1 RAs (0.76, 0.61-0.94). In contrast, DPP-4 inhibitors did not reduce MACE or mortality compared to placebo and were associated with higher all-cause mortality compared to the SGLT-2 inhibitor (1.53, 1.24-1.89) and GLP-1 RAs (1.16, 1.01-1.33).

Conclusions: All-cause mortality and MACE were reduced by the SGLT-2 inhibitor and GLP-1 RAs, but not DPP-4 inhibitors. The SGLT-2 inhibitor had the most beneficial impact on all-cause mortality. DPP-4 inhibitors showed no cardiovascular benefit and were inferior to the other two drug classes in preventing deaths.

Keywords: Antidiabetic drugs; Cardiovascular risk; Network meta-analysis; Type 2 diabetes mellitus.

Publication types

  • Meta-Analysis

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic / methods*
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Treatment Outcome


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucagon-Like Peptide 1