SGLT2 inhibitors outperform GLP-1 receptor agonists for kidney protection in type 2 diabetes
- 02-02-2026
- Diabetic Nephropathy
- Editor's Choice
- News
medwireNews: People with type 2 diabetes treated with a sodium-glucose cotransporter (SGLT)2 inhibitor may be better protected against chronic kidney disease (CKD) and acute kidney injury (AKI) than those given a glucagon-like peptide (GLP)-1 receptor agonist, research shows.
The findings “underscore the potential of SGLT2 [inhibitor] treatment for primary prevention of kidney disease in individuals with type 2 diabetes,” say Simon Jensen (Aarhus University Hospital, Denmark) and co-investigators.
They used Danish population-based data to carry out an emulated target trial that included 36,279 individuals (median age 63 years, 64% men) who initiated an SGLT2 inhibitor (empagliflozin or dapagliflozin) between 2014 and 2020, and 18,782 people (median age 61 years, 58% men) who initiated a GLP-1 receptor agonist (liraglutide, semaglutide, or dulaglutide) during the same period.
At baseline, all participants were already receiving metformin treatment and the two groups had similar diabetes duration, estimated glomerular filtration rate (eGFR), and urine albumin–creatinine ratio (uACR).
The researchers report in JAMA Internal Medicine that, during 5 years of follow-up, the risk for CKD was a significant 19% lower with SGLT2 inhibitor use than with GLP-1 receptor agonist use, occurring at rates of 6.7% and 8.2%, respectively.
The 5-year mean cumulative count of AKI was also significantly lower in the SGLT2 inhibitor group than in the GLP-1 receptor agonist group, at 25.2 versus 28.7 per 100 individuals.
When assessing the 5-year incidence of secondary outcomes, the team found that SGLT2 inhibitor users had a significant 25% lower risk for a sustained reduction in eGFR than GLP-1 receptor agonist users (4.1 vs 5.4%) and a significant 23% lower risk for kidney failure (0.2 vs 0.3%).
Conversely, the 5-year risk for incident progressive albuminuria was a significant 7% higher with SGLT2 inhibitors versus GLP-1 receptor agonists (16.1 vs 15.0%). The 5-year mortality rate was also higher in the former group than in the latter (9.7 vs 9.3%) but not significantly so, while the rate of severe albuminuria was 3.2% in both groups.
Jensen et al comment that “the divergent outcomes of eGFR and albuminuria suggest that combined treatment may offer additive benefits, which should be explored in future studies.”
Subgroup analyses showed that the results were generally consistent by sex, age, eGFR, uACR, glycated hemoglobin level, atherosclerotic cardiovascular disease status, heart failure status, and diabetes duration, but suggested that the greatest reductions in CKD and AKI with SGLT2 inhibitor use occurred among individuals without pre-existing kidney disease.
“Collectively, these findings support a lower risk of acute and chronic kidney outcomes with SGLT2 [inhibitors] vs GLP-1 [receptor agonists], especially among individuals with a low a priori risk of kidney disease,” the authors remark.
They add that using comprehensive population-based data “allowed for a representative and granular assessment of kidney outcomes, strengthening the relevance and impact of our findings for everyday clinical care.”
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