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Cardiovascular efficacy and safety of antidiabetic agents: A network meta-analysis of randomized controlled trials

Minji Sohn1, Juan P Frias2, Soo Lim1

  • 1Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.

Diabetes, Obesity & Metabolism
|August 31, 2023
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) reduce major adverse cardiovascular events (MACEs). SGLT-2is offer superior renal protection, while GLP-1 RAs benefit both cardiovascular and renal health.

Area of Science:

  • Cardiology
  • Nephrology
  • Endocrinology

Background:

  • Glucose-lowering therapies (GLTs) are crucial for managing diabetes and preventing cardiovascular complications.
  • Understanding the comparative cardiorenal efficacy and safety profiles of various GLTs is essential for clinical decision-making.

Purpose of the Study:

  • To investigate the cardiorenal efficacy and general safety of different classes of GLTs.
  • To compare the effects of GLTs on major adverse cardiovascular events (MACEs) and heart failure.

Main Methods:

  • A systematic search of PubMed, Embase, and Cochrane databases was conducted for multicentre, randomized clinical trials.
  • Trials included over 100 participants, comparing antidiabetic agents against placebo or other antidiabetic agents.
  • Random-effects network meta-analyses were performed to estimate hazard ratios for cardiorenal outcomes and safety events.

Main Results:

  • Forty-three trials involving nine GLT classes were analyzed.
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT-2is), and thiazolidinediones reduced the risk of three-point MACEs compared to placebo, dipeptidyl peptidase-4 inhibitors, or insulin.
  • SGLT-2is demonstrated superior renal outcome benefits, reducing them by approximately 40%. GLP-1 RAs showed favorable cardiovascular and renal outcomes.
  • Thiazolidinedione therapy was associated with increased risks of heart failure hospitalization and no mortality benefits. Adverse events leading to discontinuation were higher for GLP-1 RAs and thiazolidinediones.

Conclusions:

  • GLP-1 RAs, SGLT-2is, and thiazolidinediones effectively reduce three-point MACEs compared to other GLTs.
  • Each GLT class possesses distinct advantages and disadvantages regarding cardiorenal protection and safety.
  • SGLT-2is are particularly effective for renal outcomes, while GLP-1 RAs offer broad cardiorenal benefits.
Keywords:
adverse reactionshypoglycaemic agentsmajor adverse cardiac eventsnetwork meta-analysisrenal outcomes

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