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Comparative cardiovascular efficacy of antidiabetic therapies in type 2 diabetes: a systematic review and network

Donya Mohammadi1, Behnam Sadeghirad2, Mohammad Aziz Rasouli1,3

  • 1Social Determinant of the Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Diabetology & Metabolic Syndrome
|June 27, 2026
PubMed

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduce cardiovascular risks in type 2 diabetes mellitus (T2DM) patients. GLP-1 RAs lower mortality and stroke, while SGLT2 inhibitors reduce heart failure and hospitalizations.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Cardiovascular diseases (CVDs) are the primary cause of death in type 2 diabetes mellitus (T2DM).
  • Antidiabetic medications and combination therapies are crucial for managing T2DM and its complications.
  • Evaluating comparative efficacy of treatments for CVD outcomes in T2DM is essential.

Purpose of the Study:

  • To conduct a systematic review and network meta-analysis.
  • To compare the efficacy of various antidiabetic medications and combination therapies.
  • To assess the impact on cardiovascular outcomes in T2DM patients.

Main Methods:

  • Searched major databases (PubMed, Embase, Web of Science, Scopus, CENTRAL) for RCTs up to December 2024.
  • Included RCTs on metformin, sulfonylureas, TZDs, DPP-4 inhibitors, GLP-1 RAs, SGLT2 inhibitors, and insulin.
  • Analyzed outcomes including cardiovascular mortality, MI, stroke, heart failure, and hospitalizations using random-effects models.

Main Results:

  • Included 133 RCTs with 289,558 participants (mean age 64.7 years).
  • GLP-1 RAs significantly reduced cardiovascular mortality (RR 0.85) and stroke (RR 0.83) with high certainty.
  • SGLT2 inhibitors significantly reduced heart failure (RR 0.64) and cardiovascular hospitalizations (RR 0.72) with high certainty.

Conclusions:

  • GLP-1 RAs and SGLT2 inhibitors demonstrate significant benefits for specific cardiovascular outcomes in T2DM.
  • These classes of drugs are particularly effective in reducing cardiovascular mortality, stroke, heart failure, and hospitalizations.
  • Treatment decisions should consider patient-specific risk profiles and cost-effectiveness for optimal management.
Abstract

Keywords:
Cardiovascular DiseasesEvidence SynthesisPharmacological InterventionsType 2 Diabetes Mellitus

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