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SGLT2 Inhibitors vs GLP-1 Receptor Agonists for Kidney Outcomes in Individuals With Type 2 Diabetes.
Simon K Jensen1,2,3, Uffe Heide-Jørgensen1,2, Ina T Andersen1,2
1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
JAMA Internal Medicine
|January 20, 2026
Summary
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) show greater effectiveness than glucagon-like peptide-1 receptor agonists (GLP-1RA) in preventing chronic kidney disease (CKD) and acute kidney injury (AKI) in type 2 diabetes patients.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Randomized clinical trials directly comparing SGLT2i and GLP-1RA for kidney outcomes are lacking.
- Type 2 diabetes is a leading cause of chronic kidney disease (CKD) and acute kidney injury (AKI).
Purpose of the Study:
- To compare the effectiveness of SGLT2i versus GLP-1RA in reducing CKD and AKI in individuals with type 2 diabetes.
- To evaluate the impact of these treatments on secondary kidney-related outcomes and mortality.
Main Methods:
- Emulation of a target trial using nationwide Danish registry data from metformin-treated type 2 diabetes patients initiating SGLT2i or GLP-1RA.
- Coprimary outcomes: CKD (defined by eGFR decline, kidney failure, or severe albuminuria) and AKI.
- Intention-to-treat analysis using inverse probability of treatment weights, with Aalen-Johansen estimator for CKD and mean cumulative counts for AKI.
Main Results:
- SGLT2i initiation was associated with a lower 5-year risk of CKD (6.7% vs 8.2%) and a lower 5-year AKI burden (25.2 vs 28.7 events per 100 individuals) compared to GLP-1RA.
- GLP-1RA initiators showed slightly reduced risks of albuminuria and mortality.
- SGLT2i demonstrated greater benefits in individuals without pre-existing kidney disease.
Conclusions:
- SGLT2i treatment is associated with a reduced risk of CKD and AKI compared to GLP-1RA in type 2 diabetes.
- SGLT2i may be a preferred option for the primary prevention of kidney disease in this population.
- Further research should explore long-term comparative effectiveness and safety profiles.
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