Understanding the Shared Pathways of Diabetes and Heart Failure

Over the past decade, epidemiological and clinical evidence have shown how frequently diabetes and heart failure intersect. Heart failure is now recognized as one of the most common cardiovascular outcomes in people with diabetes, while insulin resistance and new‑onset diabetes are highly prevalent among those with chronic heart failure. Large cohorts suggest that diabetes substantially increases the likelihood of developing heart failure, and when the two coexist, the risks of rehospitalization and mortality rise markedly. Yet these observations are still sometimes interpreted as coincidental, rather than reflective of shared mechanisms. Our aim was to bring these findings into a unified, practical framework.
We approached this through the concept of the glucovascular continuum, which frames diabetes and heart failure as interconnected and mutually reinforcing components of cardiometabolic disease. Rather than viewing metabolic and cardiovascular dysfunction as parallel processes, the continuum emphasizes how disturbances in glucose metabolism, vascular health and myocardial function gradually evolve simultaneously and progressively.
Multiple cellular disturbances, including altered metabolism, mitochondrial dysfunction, oxidative stress, and inflammatory signalling, contribute to myocardial injury in diabetes. Rather than exhaustively detailing these, we highlight how these disturbances translate into early functional changes in the heart, reduced cardiac efficiency, and, over time, the development of clinically evident heart failure.
Crucially, this relationship is bidirectional. Once heart failure develops, it worsens insulin resistance and glucose dysregulation through neurohormonal activation, skeletal‑muscle metabolic alterations and systemic inflammation. Following an initial hospitalization due to heart failure, new-onset diabetes occurs in many patients over the subsequent years and is associated with poorer survival. Together, these patterns highlight how each condition amplifies the other.
Understanding diabetes and heart failure within a shared continuum also clarifies how therapeutic advances exert benefit. Recent developments highlight that several glucose‑lowering agents have effects extending meaningfully beyond glycaemic control. Sodium–glucose cotransporter‑2 inhibitors consistently reduce heart‑failure hospitalizations and cardiovascular death, including among individuals already living with heart failure regardless of diabetes status. Glucagon‑like peptide‑1 receptor agonists such as semaglutide improve heart‑failure‑related symptoms, physical limitations and overall cardiovascular outcomes in high‑risk cardiometabolic populations. Mineralocorticoid receptor antagonists like finerenone have demonstrated fewer new heart‑failure events and improved cardiovascular and kidney outcomes in people with diabetes. Together, these agents alleviate metabolic stress, vascular inflammation and cardiac workload, preventing hospitalizations, limiting progression to symptomatic heart failure, and reducing premature cardiovascular mortality.
Our review did not catalogue clinical trials individually. Instead, we emphasized the conceptual shift these therapies represent: treating metabolic and cardiovascular dysfunction as interlinked rather than siloed processes. At the same time, we highlight that certain glucose‑lowering therapies may worsen heart‑failure outcomes and should be used with caution. These insights support more closely aligned management strategies and deeper collaboration across specialties.
Important questions remain. Future research must clarify when and where the glucovascular continuum begins, and how its various stages contribute to distinct cardiovascular outcomes. Emerging evidence suggests that glucovasculopathy affects multiple organ systems, including the heart, kidneys and retina. A better understanding of how early injury in one system accelerates disease in another could sharpen risk prediction and allow earlier intervention.
We hope that viewing diabetes and heart failure as interconnected manifestations of a shared cardiometabolic process will encourage earlier recognition of risk, more integrated care models, and broader interdisciplinary collaboration. By shifting focus from isolated diagnoses to shared pathways, clinicians and researchers may uncover new opportunities to interrupt progression before irreversible damage occurs.