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

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.