Superior renal benefits of SGLT2 inhibitors in type 2 diabetes highlighted in comparative study

Initiating treatment with a sodium–glucose cotransporter-2 (SGLT2) inhibitor rather than a glucagon-like peptide-1 receptor agonist (GLP-1RA) is associated with better renal outcomes in people with type 2 diabetes, according to recent research.

Researchers from Aarhus University Hospital and Aarhus University, alongside teams from Denmark, Sweden and the Netherlands, conducted a large population-based comparative effectiveness study to compare the effectiveness of SGLT2 inhibitors and GLP-1RAs in reducing both chronic and acute renal outcomes in individuals with type 2 diabetes – an area where randomised head-to-head trial data are lacking.

The study used a target trial emulation framework and linked Danish national health register data to identify adults with metformin-treated type 2 diabetes who initiated either an SGLT2 inhibitor or a GLP-1 RA between January 2014 and November 2020, with follow-up extending to October 2024.

In total, 36,279 individuals initiated an SGLT2 inhibitor (mean age 63 years) and 18,782 initiated a GLP-1RA (mean age 61 years). Baseline characteristics of diabetes duration, kidney function and albuminuria were similar across groups.

CKD risk and SGLT2 inhibitors

The two co-primary outcomes were chronic kidney disease (CKD) – defined as a 40% decline in estimated glomerular filtration rate (eGFR), severe albuminuria, or kidney failure – and acute kidney injury (AKI).

Following inverse probability-based weighting to balance 44 baseline covariates, the five-year risk of CKD was 6.7% in the SGLT2 inhibitor group and 8.2% among GLP-1RA initiators. This resulted in a risk ratio of 0.81 (95% CI 0.76–0.87) and an absolute risk reduction of 1.5 percentage points.

The risk of AKI was also lower in the SGLT2 inhibitor group. Over five years, their mean cumulative number of AKI events per 100 individuals was 25.2, compared with 28.7 among GLP-1RA users, yielding a mean cumulative count ratio of 0.88 (95% CI 0.83–0.93).

The reduction in CKD risk associated with SGLT2 inhibitors was primarily attributable to lower risks of sustained eGFR decline and kidney failure, while the risk of severe albuminuria remained similar between groups.

Secondary outcomes and future research

In contrast, secondary outcomes showed slightly lower risks of new or worsening albuminuria and death among GLP-1RA users. Over five years, mortality was 9.7% in the SGLT2 inhibitor group and 9.3% in the GLP-1RA group, but the difference was not statistically significant in intention-to-treat analyses.

Subgroup analyses suggested that the renal-protective benefits of SGLT2 inhibitors were greatest in individuals without pre-existing kidney disease.

While the study provided head-to-head evidence, several limitations were noted, including the absence of data on body mass index, potential residual confounding due to non-randomised treatment allocation, and limited generalisability beyond Nordic populations, the authors said.

Nevertheless, they concluded that SGLT2 inhibitors are associated with lower risks of chronic and acute kidney disease than GLP-1RAs, and that the evidence supports the preferential use of SGLT2 inhibitors for renal protection in people with type 2 diabetes, particularly for primary prevention.

Future research is now needed to determine whether combination therapy offers additional additive benefits, they added.

Previous studies have shown that both physical activity and coffee consumption can reduce CKD risk in type 2 diabetes.

Reference
Jensen SK et al. SGLT2 Inhibitors vs GLP-1 Receptor Agonists for Kidney Outcomes in Individuals With Type 2 Diabetes. JAMA Intern Med 2026;Jan 20:e257409.