Narrative review supports SGLT-2i use in cardiovascular-kidney-metabolic syndrome

Photo by Dmytro Vynohradov / Unsplash

Frontiers in Medicine Published April 24, 2026 Medically reviewed April 24, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider SGLT-2i for patients with stages 2–4 CKM syndrome, especially those with CKD or diabetes, based on qualitative evidence.

This narrative review synthesizes existing evidence on the use of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) in patients with cardiovascular-kidney-metabolic (CKM) syndrome, specifically those with stages 2–4 disease, including individuals with chronic kidney disease or diabetes. The review covers a broad range of outcomes including glycemic control, body weight, blood pressure, renal outcomes, and cardiovascular outcomes. The authors report that SGLT-2i therapy is associated with improvements across all these domains, with glycemic control improved, body weight reduced, blood pressure lowered, and both renal and cardiovascular outcomes improved. However, the review does not provide specific effect sizes, confidence intervals, or p-values for any of these findings, nor does it describe the methods used to select or synthesize the included studies. No limitations are acknowledged by the authors, and details on funding, conflicts of interest, and safety outcomes are not reported. The review recommends SGLT-2i for patients with stages 2–4 CKM syndrome, particularly those with CKD or diabetes, to delay disease progression and improve long-term clinical outcomes. Given the narrative design and lack of quantitative synthesis, these conclusions should be interpreted as a qualitative summary of the literature rather than a definitive evidence base. Clinicians should consider this review as supportive but not conclusive, and should consult primary sources or meta-analyses for more precise estimates of benefit.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined clinical entity that encompasses cardiovascular disease (CVD), chronic kidney disease (CKD) and metabolic disorders. It has emerged as a growing public health concern that adversely affects the quality of life and imposes a substantial burden on human health. Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) is a novel class of oral hypoglycemic agent with novel insulin-independent mechanism. In the last decade, published studies highlight its substantial effects on renal and cardiovascular outcomes. SGLT-2i is recommended for patients with stages 2–4 CKM syndrome, particularly those with CKD or diabetes to delay disease progression, and improve long-term clinical outcomes. This review comprehensively summarizes the current clinical evidence and elucidates the underlying mechanisms of SGLT-2i in CKM syndrome. Glycosuria and natriuresis, the primary effects of SGLT2 inhibition, play a pivotal role in improving glycemic control, reducing body weight, and lowering blood pressure. These initial effects trigger a cascade of downstream mechanisms: hemodynamic optimization via interstitial fluid reduction, enhanced cardiac efficiency through ketogenesis, and attenuation of inflammation and oxidative stress. Additional systemic benefits include increased fatty acid utilization, reduced hyperuricemia and stimulated erythropoiesis, thereby generating a network of interrelated therapeutic benefits in CKM syndrome. The pleiotropic effects of SGLT-2i position it as a highly promising therapeutic strategy for CKM syndrome. A deeper understanding of underlying mechanisms will better inform the application of SGLT-2i for this newly defined condition and guide optimal treatment strategies.