The rising prevalence of obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD)—a condition characterized by hepatic steatosis and metabolic impairment—along with their cardiovascular complications, underscores the urgent need to promote physical activity. Exercise triggers the release of exerkines — a diverse group of signaling molecules including cytokines, lipids, nucleic acids, peptides, and metabolites — that act via endocrine, paracrine, and autocrine mechanisms. Many exerkines are packaged into extracellular vesicles, enabling their transport and communication between distant tissues. These signals mediate local and systemic adaptations with potential therapeutic implications.

While initial studies focused on myokines, it is now clear that organs such as the liver, adipose tissue, heart, and skeletal muscle also contribute to the exerkine network. Advances in multi-omics and systems biology are revealing how these exercise-induced signals modulate key metabolic and inflammatory pathways across tissues. These insights are shedding new light on the pathophysiology of diabetes and cardiovascular disease and may inform the development of personalized interventions to prevent or treat cardiometabolic disorders. This new Collection welcomes submissions in, but not limited to, the following areas:

- The metabolic and molecular effects of acute and chronic exercise in humans and animal models.

- Exerkine-mediated signal transduction pathways (e.g., AMPK, mTOR, PGC-1α).

- Multi-omics profiling of exercise responses (e.g., metabolomics, transcriptomics, epigenomics).

- Sex, modality, intensity, and duration as modulators of exerkine release and action.

- Translational potential of exerkines in treating diabetes and the Cardiovascular-Kidney-Metabolic (CKM) syndrome.

This Collection welcomes original research articles, meta-analyses, and review articles. Submissions using preclinical, translational, or clinical approaches are all considered.

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 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.

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.

This Collection is a Sister Collection with Cardiovascular Diabetology – Endocrinology Reports.

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.