SGLT2 Inhibitors and GLP/GIP/Glucagon Agonists: From Fundamental Mechanisms to Clinical Translation
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".
Deadline for manuscript submissions: 31 July 2026 | Viewed by 26
Special Issue Editor
Interests: sustainability in public health; occupational medicine; environment-associated diseases; sick building syndrome; one health
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Special Issue Information
Dear Colleagues,
Rationale and Significance
Sodium–glucose cotransporter 2 (SGLT2) inhibitors and incretin-based multi-agonists targeting GLP-1, GIP and glucagon receptors have reshaped the therapeutic landscape of metabolic diseases. Initially developed as glucose-lowering agents, these drug classes have demonstrated broad benefits extending to cardiovascular, renal, hepatic and adipose tissue health, with implications for heart failure, chronic kidney disease, obesity and metabolic-dysfunction-associated steatotic liver disease (MASLD).
Despite remarkable clinical success, critical questions remain regarding their fundamental mechanisms of action, tissue-specific signaling pathways, long-term adaptations and pleiotropic effects beyond glycemic control. Parallel advances in medicinal chemistry, structural biology, systems metabolism and translational physiology now provide unprecedented opportunities to integrate mechanistic insights with clinical outcomes.
This Special Issue aims to bridge fundamental research and clinical investigation, providing a comprehensive and interdisciplinary forum to examine how SGLT2 inhibitors and GLP/GIP/glucagon receptor agonists work—from molecular and cellular mechanisms to human physiology and real-world clinical impacts.
Aims and Objectives
The objectives of this Special Issue are to
- Elucidate molecular, cellular and organ-level mechanisms underlying the actions of SGLT2 inhibitors and incretin-based multi-agonists;
- Integrate preclinical discoveries with clinical trial data and real-world evidence;
- Highlight emerging therapeutic indications and novel combination strategies;
- Identify unmet needs, controversies and future research directions in metabolic, cardiovascular and renal medicine.
Scope and Topics
We invite original research articles, reviews, mini-reviews and perspectives covering, but not limited to, the following topics:
Fundamental and Preclinical Research
- Molecular mechanisms of SGLT2 inhibition in the kidney, heart, adipose tissue, liver and brain
- Incretin receptor signaling, biased agonism and receptor crosstalk (GLP-1, GIP, glucagon)
- Metabolic flexibility, mitochondrial function and energy expenditure
- Role of glucagon signaling in obesity, diabetes and fatty liver disease
- Inflammation, oxidative stress, autophagy and cellular stress responses
- Systems biology, omics and integrative metabolic modeling
- Sex differences and genetic determinants of drug response
- Cardiovascular and renal protection: Mechanisms and clinical implications
- Effects on heart failure phenotypes (HFrEF, HFpEF)
- Chronic kidney disease progression and renal hemodynamics
- Obesity, body composition and appetite regulation
- MASLD/NASH and metabolic liver disease
- Safety profiles, adverse effects and long-term outcomes
- Biomarkers of response and precision medicine approaches
- Dual and triple agonists: GLP-1/GIP, GLP-1/glucagon and GLP-1/GIP/glucagon
- Combination therapies (e.g., SGLT2 inhibitors plus incretin agonists)
- Novel drug delivery systems and next-generation molecules
- Clinical trial design, endpoints and regulatory considerations
- Real-world evidence and health economics
Dr. Cosmin Mihai Vesa
Guest Editor
Manuscript Submission Information
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Keywords
- SGLT2 inhibitors
- GLP-1 receptor agonists
- GIP
- glucagon
- multi-agonists
- cardiometabolic disease
- renal protection
- obesity
- translational research
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