Despite advancements in glycemic control, cardiovascular disease remains the leading cause of morbidity in diabetes. The plateau in clinical outcomes suggests that we may have overlooked a complex, multi-organ communication network—the vasculome. This Collection seeks to move beyond traditional glucocentric frameworks to better understand endothelial biology as a dynamic interface integrating metabolic, immune, neural, and hormonal signals. We focus on the concept of the endothelial interactome, a heterogeneous and spatially diverse regulatory system that contributes to vascular dysfunction, organ-specific complications, and cardiometabolic risk.

The aim of this Collection is to provide a high-impact platform for research that characterizes site-specific endothelial heterogeneity and its interactions with peripheral organ systems in cardiometabolic disease. We particularly encourage studies that identify molecular and cellular “signatures” (e.g., angiokines, inflammatory mediators, and metabolic regulators) that contribute to organ-specific vascular complications. By integrating systems biology approaches with clinical and translational data, we aim to advance understanding of disease mechanisms and identify novel targets for prevention, risk stratification, and precision therapy, including strategies that address persistent vascular dysfunction despite metabolic control.

We welcome original research articles, clinical investigations, observational cohort studies, randomized clinical trials, high-level reviews, and translational perspectives.

Topics of interest include, but are not limited to:

• Neuro-Immune-Vascular Axis: Interactions between autonomic regulation, immune activation, and vascular inflammation in cardiometabolic disease
• Sex as a Biological Variable: Sex-specific mechanisms contributing to vascular complications in diabetes and metabolic disease
• Epigenetic and Immune Memory: Mechanisms of vascular “trained immunity” and potential strategies for reversal or modulation
• Systems Medicine Approaches: Multi-omics, computational modeling, and organ-on-a-chip platforms to study endothelial heterogeneity and inter-organ communication
• Clinical Translation: Biomarkers, imaging approaches, and therapeutic strategies targeting vascular dysfunction and improving cardiovascular outcomes in diabetes and related metabolic disorders

We invite contributions that bridge basic, translational, and clinical research to advance a more integrated understanding of vascular disease in cardiometabolic disorders. Our goal is to translate mechanistic insights into meaningful clinical outcomes that improve prevention, diagnosis, and treatment in metabolic disease.

All submissions in this Collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the Editor-in-Chief. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com or the Editor-in-Chief.

Cardiovascular Diabetology features a Collection on "Incretin-Based Therapies in Type 2 Diabetes and Obesity: Current Evidence and the Evolving Cardiometabolic Landscape". This is a companion Collection with Cardiovascular Diabetology - Endocrinology Reports with the title "Pleiotropic Actions of Incretin-Based Therapies" and with BMC Endocrine Disorders with the title "Incretin-based therapies for cardiometabolic disease: mechanisms and clinical outcome".

Building upon the growing recognition of cardiometabolic organ protection as a central therapeutic goal, incretin-based therapies have reshaped the management of type 2 diabetes and obesity, extending their clinical relevance far beyond glycemic control. Large-scale cardiovascular outcome trials (CVOTs) have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce major adverse cardiovascular events (MACE), redefining cardiometabolic risk management and influencing contemporary therapeutic strategies. Targeting the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) pathways, these agents enhance glucose-dependent insulin secretion, promote weight reduction, and exert multi-organ effects. Growing evidence supports their impact on vascular function, myocardial metabolism, renal protection, metabolic dysfunction-associated steatotic liver disease (MASLD), and systemic inflammation.

Three principal pharmacological approaches currently characterize incretin-based therapy:

• GLP-1 receptor agonists (GLP-1RAs), mostly injectable medications with proven improved cardiovascular outcomes and weight-reduction.
• Dual GIP/GLP-1 receptor agonists, newer solely injectable medications designed to enhance glycemic control and weight-reduction efficacy.
• DPP-4 inhibitors (also known as gliptins), oral medications which modestly increase endogenous incretin levels and have no impact on cardiovascular outcomes or body weight.

Beyond glucose lowering, incretin-based therapies are increasingly positioned within the broader cardiometabolic framework, with emerging data supporting cardiovascular and renal protection, as well as effects on endothelial function, atherosclerosis, heart failure phenotypes, and chronic kidney disease progression.

Areas of interest include, but are not limited to:

• Classic antidiabetic, anti-obesity and cardioprotective effects
• Cardiovascular outcomes and mechanistic correlates
• Endothelial and vascular biology
• Myocardial metabolism and heart failure subtypes
• Novel renal and hepatoprotective actions
• Optimization and individualized use of existing GLP-1 receptor agonists
• Development of novel GLP-1 receptor agonists and multi-agonist (dual and triple) strategies
• Emerging extra-metabolic actions, including anti-inflammatory and neuroprotective effects
• Combination therapies, including co-formulations with insulin or SGLT2 inhibitors
• Innovative delivery systems, including non-injectable and implantable approaches
• Real-world comparative effectiveness, long-term safety, adherence and treatment durability

This Collection welcomes original research, translational studies, and comprehensive reviews and meta-analyses that provide novel mechanistic insight or clinically relevant evidence to advance understanding of the expanding role of incretin-based therapies in cardiometabolic medicine.

This Collection supports and amplifies research related to SDG 3, Good Health and Well-Being.

All submissions in this Collection undergo the journal’s standard peer review process. Similarly, all manuscripts authored by a Guest Editor(s) will be handled by the journal editorial board. As an open access publication, this journal levies an article processing fee (details here). We recognize that many key stakeholders may not have access to such resources and are committed to supporting participation in this issue wherever resources are a barrier. For more information about what support may be available, please visit OA funding and support, or email OAfundingpolicy@springernature.com.