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Type 2 diabetes and risk of heart failure: a systematic review and meta-analysis from cardiovascular outcome trials

Dario Giugliano1, Maria Ida Maiorino2, Miriam Longo3

  • 1Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, Università della Campania L. Vanvitelli, Naples, Italy. dario.giugliano@unicampania.it.

Endocrine
|April 28, 2019
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) significantly reduce heart failure risk in type 2 diabetes patients. Dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) showed neutral effects on heart failure risk.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF).
  • Several classes of anti-hyperglycemic medications are used in T2D management, including DPP-4i, GLP-1 RAs, and SGLT-2i.
  • The cardiovascular safety profiles of these drug classes, particularly concerning HF risk, require thorough evaluation.

Purpose of the Study:

  • To evaluate the effect of DPP-4i, GLP-1 RAs, and SGLT-2i on the risk of heart failure in patients with T2D through a meta-analysis of randomized controlled trials (RCTs).
  • To determine if any observed effects are related to glycemic control.

Main Methods:

  • A systematic meta-analysis of RCTs comparing DPP-4i, GLP-1 RAs, or SGLT-2i as add-on therapy to placebo in patients with T2D.
  • The primary outcome was hospitalization for heart failure.
  • Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a random-effect model.

Main Results:

  • Twelve RCTs involving 120,765 patients were included.
  • Overall, these anti-hyperglycemic drugs showed a non-significant 10% reduction in HF risk (HR=0.90, 95% CI 0.80-1.01).
  • SGLT-2 inhibitors demonstrated a significant 31% reduction in HF risk (HR=0.69, 95% CI 0.61-0.79) with no heterogeneity, suggesting a class effect. DPP-4i and GLP-1 RAs showed non-significant modifications in HF risk (+5% and -9%, respectively). Meta-regression indicated no association between HbA1C reduction and HF risk reduction.

Conclusions:

  • Sodium-glucose cotransporter-2 inhibitors significantly reduce heart failure risk in patients with type 2 diabetes, independent of glycemic control.
  • Dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists appear to have a neutral effect on heart failure risk in this population.
  • These findings highlight the specific cardioprotective benefits of SGLT-2 inhibitors in T2D management.
Keywords:
DPP-4iGLP-1 RAsHeart failureMACESGLT-2iType 2 diabetes

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