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SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular-Kidney-Metabolic Syndrome
Aryan Gajjar1,2, Arvind Kumar Raju3, Amani Gajjar2
1Department of Internal Medicine, Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Biomedicines
|August 28, 2025
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) show promise for treating Cardiovascular-Kidney-Metabolic (CKM) syndrome. Combination therapy may offer synergistic benefits for patients with CKM syndrome.
Area of Science:
- Cardiology
- Nephrology
- Endocrinology
- Metabolic Diseases
Background:
- Cardiovascular-Kidney-Metabolic (CKM) syndrome encompasses obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease, accelerating adverse outcomes.
- Coexisting CKM conditions significantly increase morbidity and mortality.
- Emerging evidence highlights the organ-protective functions of GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i).
Purpose of the Study:
- To evaluate the mechanistic rationale, clinical evidence, and therapeutic potential of GLP-1RA and SGLT2i in CKM syndrome.
- To assess the synergistic effects and clinical utility of combination therapy with GLP-1RA and SGLT2i for CKM syndrome.
- To discuss current recommendations, clinical evidence, and mechanistic insights for these drug classes in CKM syndrome management.
Main Methods:
- Review of existing literature on GLP-1RA and SGLT2i mechanisms and clinical trials.
- Analysis of studies investigating individual and combination therapies in CKM syndrome.
- Evaluation of data on glycemic control, weight loss, cardiovascular, and renal outcomes.
Main Results:
- SGLT2i demonstrate benefits in heart failure, hemodynamic regulation, and renal protection.
- GLP-1RA show efficacy in glycemic management, weight reduction, and reducing atherosclerotic cardiovascular disease risk.
- Combination therapy exhibits potential synergistic effects, though underutilized due to guidelines, cost, and access.
Conclusions:
- Early and combined use of GLP-1RA and SGLT2i may be crucial for managing CKM syndrome.
- These agents represent a significant shift towards patient-centered cardiometabolic therapy.
- Further research and guideline development are needed to optimize combination therapy for CKM syndrome.
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