SGLT2 Inhibitors Better for Kidney Health Than GLP-1RAs in Type 2 Diabetes: Study

Individuals newly diagnosed with type 2 diabetes may benefit from starting with an SGLT2 inhibitor rather than a GLP-1 receptor agonist to protect their kidney health, according to a recent study published in January 2026 in JAMA Internal Medicine. The research, a large population-based comparative effectiveness study, found that initiating treatment with an SGLT2 inhibitor was associated with a lower risk of chronic kidney disease and fewer acute kidney injury events compared to starting with a GLP-1RA.

Researchers from Denmark, Sweden and the Netherlands analyzed data from Danish national health registers, focusing on adults with type 2 diabetes treated with metformin who began either an SGLT2 inhibitor or a GLP-1RA between January 2014 and November 2020. They followed these individuals through October 2024 to assess kidney-related outcomes.

The study included 36,279 individuals who initiated an SGLT2 inhibitor, with an average age of 63, and 18,782 who initiated a GLP-1RA, with an average age of 61. Importantly, baseline characteristics such as diabetes duration, kidney function, and levels of albuminuria were comparable between the two groups, suggesting a fair comparison.

Understanding the Kidney Outcomes

The researchers focused on two primary outcomes: chronic kidney disease (CKD), defined as a 40% reduction in estimated glomerular filtration rate (eGFR), severe albuminuria, or kidney failure; and acute kidney injury (AKI). Using statistical methods to account for differences in patient characteristics, they found a significant difference in the five-year risk of CKD. The risk was 6.7% in the SGLT2 inhibitor group compared to 8.2% in the GLP-1RA group, representing a 1.5 percentage point absolute risk reduction.

The study also revealed a lower risk of AKI among those starting with an SGLT2 inhibitor. Over five years, SGLT2 inhibitor users experienced a mean cumulative count of 25.2 AKI events per 100 individuals, while GLP-1RA users experienced 28.7 events. This translates to an approximately 12% reduction in AKI burden with SGLT2 inhibitors.

The observed reduction in CKD risk with SGLT2 inhibitors was largely driven by lower risks of sustained eGFR decline and progression to kidney failure. The levels of albuminuria, a marker of kidney damage, remained similar between the two treatment groups.

Nuances in Secondary Outcomes

While SGLT2 inhibitors demonstrated a clear advantage in kidney protection, the study also revealed some differences in secondary outcomes. GLP-1RA users showed slightly lower risks of new or worsening albuminuria and a trend towards lower mortality, although this difference in mortality (9.7% in the SGLT2 inhibitor group versus 9.3% in the GLP-1RA group) was not statistically significant.

Subgroup analysis indicated that the kidney-protective benefits of SGLT2 inhibitors were most pronounced in individuals without pre-existing kidney disease, suggesting a potential role for these medications in primary prevention of kidney complications in diabetes.

Study Limitations and Future Directions

The researchers acknowledge several limitations to their study. Data on body mass index (BMI) were not available, which could influence the results. As an observational study using registry data, there is a possibility of residual confounding despite efforts to statistically balance the groups. The study population was primarily of Nordic descent, which may limit the generalizability of the findings to other populations.

Despite these limitations, the study authors concluded that SGLT2 inhibitors are associated with lower risks of both chronic and acute kidney disease compared to GLP-1RAs in individuals with type 2 diabetes. They suggest that these findings support the preferential use of SGLT2 inhibitors for renal protection, particularly in patients without established kidney disease.

The researchers also highlighted the need for future studies to investigate whether combining SGLT2 inhibitors and GLP-1RAs could provide even greater additive benefits for kidney and cardiovascular health. This is an area of active research, as both drug classes have demonstrated individual benefits in clinical trials.

It’s important to note that lifestyle factors also play a crucial role in kidney health. Previous research has shown that regular physical activity and even moderate coffee consumption can contribute to reducing the risk of chronic kidney disease in people with 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.