Glucagon-like peptide-1 receptor agonists (GLP1-RA) improve cardiovascular outcomes in patients with type 2 diabetes (T2D). However, some studies suggest that their effects in patients with heart failure (HF) may be attenuated. We aimed to explore the effects of the GLP1-RA albiglutide on HF outcomes in patients with and without HF history enrolled in the Harmony Outcomes trial.

Myocardial fluid homeostasis relies on a complex interplay between microvascular filtration, interstitial hydration, cardiomyocyte water uptake and lymphatic removal. Dysregulation of one or more of these mechanisms may result in myocardial oedema. Interstitial and intracellular fluid accumulation disrupts myocardial architecture, intercellular communication, and metabolic pathways, decreasing contractility and increasing myocardial stiffness. The widespread use of cardiac magnetic resonance enabled the identification of myocardial oedema as a clinically relevant imaging finding with prognostic implications in several types of heart failure. Furthermore, growing experimental evidence has contributed to a better understanding of the physical and molecular interactions in the microvascular barrier, myocardial interstitium and lymphatics and how they might be disrupted in heart failure. In this review, we summarize current knowledge on the factors controlling myocardial water balance in the healthy and failing heart and pinpoint the new potential therapeutic avenues.

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.

Our aim was to study the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on the risk of any cardiovascular event in adults with overweight or obesity and without diabetes. We conducted a random-effects meta-analysis of placebocontrolled randomized controlled trials. Nine trials were eligible and, in total, 11 430 patients were included, of which 7702 (67%) were submitted to treatment with GLP-1 RA. During follow-up, 673 participants receiving GLP-1 RA treatment (8.7%) and 416 participants receiving placebo (11.2%) had a cardiovascular event. Treatment with GLP-1 RA versus placebo resulted in a reduction in the risk of any cardiovascular event (RR = 0.81, CI 0.70-0.92; p = .001). In overweight or obese adults without diabetes, treatment with GLP-1 RA reduced the risk of cardiovascular events. Our findings support the use of GLP-1 RA for reducing the cardiovascular risk of these patients.

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