Glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes with and without chronic heart failure: A meta-analysis of randomized placebo-controlled outcome trials

Diabetes Obes Metab. 2023 Jun;25(6):1495-1502. doi: 10.1111/dom.14997. Epub 2023 Feb 20.

Abstract

Aim: Glucagon-like peptide 1 receptor agonists (GLP1-RA) reduce atherosclerotic events in patients with type 2 diabetes (T2D) and a high cardiovascular risk. The effect of GLP1-RA to reduce heart failure (HF) has been inconsistent across T2D trials, and individual trials were underpowered to assess the effect of GLP1-RA according to HF history. In this meta-analysis we aim to assess the effect of GLP1-RA in patients with and without HF history in stable ambulatory patients with T2D.

Methods: Random-effects meta-analysis of placebo-controlled trials. The hazard ratio (HR) and 95% confidence intervals (95% CI) were extracted from the treatment effect estimates of HF subgroup analyses reported in each individual study. The primary outcome was a composite of HF hospitalization or cardiovascular death.

Results: In total, 54 092 patients with T2D from seven randomized controlled trials were included, of whom 8460 (16%) had HF history. Compared with placebo, GLP1-RA did not reduce the composite of HF hospitalization or cardiovascular death in patients with HF history: HR 0.96, 95% CI: 0.84-1.08, but reduced this outcome in patients without HF history: HR 0.84, 95% CI: 0.76-0.92. GLP1-RA did not reduce all-cause death in patients with HF history: HR 0.98, 95% CI: 0.86-1.11, but reduced mortality in patients without HF history: HR 0.85, 95% CI: 0.79-0.92. GLP1-RA reduced atherosclerotic events regardless of HF history: HR 0.85, 95% CI: 0.75-0.97 with HF, and HR 0.88, 95% CI: 0.83-0.93 without HF.

Conclusions: Treatment with GLP1-RA did not reduce HF hospitalizations and mortality in patients with concomitant T2D and HF, but may prevent new-onset HF and mortality in patients with T2D without HF. The reduction of atherosclerotic events with GLP1-RA was not influenced by HF history status.

Keywords: glucagon-like peptide 1 receptor agonists; heart failure; meta-analysis; treatment effects.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis* / complications
  • Cardiovascular System*
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide 1 / therapeutic use
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Heart Failure* / epidemiology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Randomized Controlled Trials as Topic

Substances

  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1