Abstract
415-P: Proteinuria and Progression of Kidney Disease in Patients with T2D Treated with SGLT2i and GLP-1RA—A Target Trial Emulation
Diabetes (New York, N.Y.), Vol.74(Supplement_1)
06/20/2025
DOI: 10.2337/db25-415-P
Abstract
Introduction and Objective: Several clinical trials have shown that SGLT2i and GLP1-RA reduce progression of kidney disease in patients with T2D. It is not known whether these medications have renoprotective effects both in patients with and without proteinuria.
Methods: We emulated a target trial using nationwide dataset from 12 US health systems and insurance plans for patients with T2D at moderate CV risk, hyperglycemia (HbA1c 7.0-11.0%) and with eGFR ≥ 45 ml/min/1.73m2 who initiated a second T2D medication after metformin between 1/1/13 and 12/31/22. We compared patients initiating a) SGLT2i or GLP1-RA or b) sulfonylureas to patients initiating DPP4i, stratifying by the presence of proteinuria (ACR ≥ 30 mg/g). We estimated 5-year risk of a composite nephropathy outcome (doubling of serum creatinine or eGFR < 15) after adjustment for demographics, comorbidities and laboratory values.
Results: We studied 76,263 patients (14,067 with and 62,196 without baseline proteinuria) followed for a median of 32 (IQR 18-57) months, with a median age of 60 (IQR 51 - 68) years and median baseline HbA1c of 7.8% (IQR 7.3% - 8.5%) Of these, 26,306 patients initiated either an SGLT2i or a GLP1-RA, 36,059 initiated a sulfonylurea and 13,898 initiated a DPP4i. A total of 1,512 (2.0%) of patients experienced the composite nephropathy endpoint. The estimated 5-year risk ratios (95% CI), compared to DPP4i, were 0.57 (95% CI 0.40-0.79) for the combined SGLT2i-GLP1-RA arm among patients with proteinuria and 1.07 (95% CI 0.86-1.32) for patients without proteinuria. Sensitivity analyses among patients with a baseline eGFR < 60 showed similar results. There was no evidence of effect modification by proteinuria for sulfonylureas vs. DPP4i.
Conclusion: Patients with T2D treated with an SGLT2i or GLP1-RA as a second agent after metformin had a lower risk of incident / worsening nephropathy compared with patients treated with DPP4i only if they had baseline proteinuria.
Details
- Title: Subtitle
- 415-P: Proteinuria and Progression of Kidney Disease in Patients with T2D Treated with SGLT2i and GLP-1RA—A Target Trial Emulation
- Creators
- ALEXANDER TurchinLUCIA PetitoEMMA HegermillerRYAN M. CarnahanANDREA R. DevriesSATYENDER GoelM Cecilia LansangMARIE E. McdonnellVINIT NairELISA L. PriestVINCENT WilleyALAN F. KaulMIGUEL Hernan
- Resource Type
- Abstract
- Publication Details
- Diabetes (New York, N.Y.), Vol.74(Supplement_1)
- DOI
- 10.2337/db25-415-P
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Publisher
- AMER DIABETES ASSOC
- Grant note
- PCORI: DB-2020C2-20308
PCORI DB-2020C2-20308
- Language
- English
- Date published
- 06/20/2025
- Academic Unit
- Epidemiology; Nursing; Injury Prevention Research Center
- Record Identifier
- 9984843602702771
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