New meta-analysis shows SGLT2 inhibitors benefit advanced CKM disease equally across stages

A recent review of 73,220 participants found that SGLT2 inhibitors provide consistent heart and kidney benefits across different stages of CKM syndrome, including severe cases, highlighting their potential for broader application in integrated cardiorenal care.

A large review in BMC Endocrine Disorders suggests that SGLT2 inhibitors deliver heart and kidney benefits across the cardiovascular-kidney-metabolic, or CKM, spectrum, including in people with more advanced disease. The analysis pooled evidence from 73,220 participants and found that the drugs were linked to fewer composite heart failure events, fewer hospital admissions for heart failure and better kidney outcomes. The authors said the pattern supports a broad cardiorenal effect, although it does not prove that the benefit is identical at every stage.

CKM syndrome is a clinical framework that connects obesity, diabetes, high blood pressure, cardiovascular disease and chronic kidney disease as overlapping parts of the same process rather than separate conditions. In the staging used by the researchers, stages 2 and 3 cover people with metabolic risk, kidney abnormalities or early cardiovascular disease, while stage 4 refers to established cardiovascular disease, kidney disease or both in the setting of metabolic risk. That distinction matters because the most advanced patients often face the highest risk of hospitalisation, progressive kidney loss and death, yet are not always well represented in conventional trials.

The meta-analysis, led by Sun, Guo and colleagues, drew on randomised trial data available through 25 February 2026. Nineteen reports from 11 parent trials met the criteria, with 18,547 participants classified as CKM stages 2 to 3 and 54,673 as stage 4. The researchers used random-effects models to pool six time-to-event outcomes, allowing for variation between studies rather than assuming every trial estimated the same effect.

The strongest signals were seen in heart failure and kidney endpoints. For the composite heart failure outcome, the hazard ratio was 0.80 in CKM stages 2 to 3 and 0.77 in stage 4, while hospitalisation for heart failure fell to 0.61 and 0.71, respectively. Kidney outcomes also favoured treatment, with hazard ratios of 0.61 in stages 2 to 3 and 0.64 in stage 4. In each case, a figure below 1 indicates fewer events in the SGLT2 inhibitor group.

Importantly, the study did not find statistically significant differences between the CKM groups. The comparisons for composite heart failure, heart failure hospitalisation and kidney outcomes all fell short of significance, meaning the available evidence did not show that one stage benefited more than the other. Still, the authors caution that the stage 2 to 3 evidence was based on fewer estimates and was therefore less precise than the stage 4 data.

The review also examined major adverse cardiovascular events and all-cause mortality. Those findings were more precise in stage 4, where the evidence base was larger, but the article did not report a clear stage-based difference for those outcomes. An exploratory test for publication bias in mortality produced a signal that could point to small-study effects, though the authors note that such tests are difficult to interpret when the number of studies is limited.

Several sensitivity analyses left the main findings intact. The researchers tested different statistical models, varied kidney endpoint definitions, excluded the SOLOIST-WHF trial because of a high-risk efficacy result, and checked whether any single study was driving the outcome. The broader picture was unchanged, strengthening confidence that the results were not an artefact of one trial or one analytical choice. Even so, the authors acknowledge the limits of mapping complex patients onto a staging system that cannot capture every clinical nuance.

The new analysis adds to a growing body of evidence that has moved SGLT2 inhibitors beyond their original role as diabetes medicines. A 2019 review in Cardiovascular Diabetology and later work in Cardiorenal Medicine have both described reductions in cardiovascular events, heart failure admissions and kidney disease progression with the drug class. More recent reviews have also argued that their effects extend across different kidney function levels and heart failure phenotypes, reinforcing their role in integrated cardiorenal care. The latest findings support that direction, while also underscoring the need for more evidence in earlier CKM disease.