Sparsentan - SGLT2 inhibitor combination therapy in trials of IgA nephropathy
- Journal
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Q1)
- Published
- 11 September 2026
- Study design
- Non-randomized / quasi-experimental trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Isabelle Ayoub, Gabriela Alperovich, Radko Komers, Laura Ann Kooienga, Alex Mercer, Stephanie Moody, et al.
- PMID
- 42726023
- DOI
- 10.1093/ndt/gfag211
Why clinicians should know about it
- Picked for Nephrology (paper of the day, 15 September 2026): Sparsentan + SGLT2i reduce proteinuria in IgAN
Abstract
BACKGROUND AND HYPOTHESIS: Sparsentan, a non-immunosuppressive, dual endothelin angiotensin receptor antagonist (DEARA), and sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduce proteinuria in patients with immunoglobulin A nephropathy (IgAN). We report the safety and efficacy of sparsentan combined with SGLT2is in patients with IgAN in the SPARTACUS trial and a substudy in the PROTECT open-label extension (OLE). METHODS: SPARTACUS (NCT05856760) was a phase 2, open-label trial in which patients had renin-angiotensin system inhibitors (RASi) replaced with sparsentan while continuing stable SGLT2i. In the PROTECT (NCT03762850) OLE substudy, patients receiving sparsentan were randomised 1:1 to add SGLT2i or continue sparsentan alone for 12 weeks; afterward, all could receive 24 weeks of sparsentan+SGLT2i combination therapy. Endpoints in both studies included change in proteinuria and safety. RESULTS: In SPARTACUS, 48 patients were enrolled (mean [SD] age, 48.9 [13.9] y; 58% male); 39 completed treatment. Replacement of RASi with sparsentan while on stable SGLT2i led to rapid urine albumin-to-creatinine ratio reductions sustained through week 24 (least-squares mean [95% CI], -56% [-66% to -3%]). In the PROTECT OLE substudy, 63 patients enrolled and completed the 12-week randomised treatment (sparsentan+SGLT2i [n=32] vs sparsentan alone [n=31]: mean [SD] age, 51.4 [13.4] y vs 50.6 [11.1] y; male 81% vs 68%, respectively); 54 completed 24 weeks of sparsentan+SGLT2i. At week 12, significant relative reductions occurred in the urine protein-to-creatinine ratio (least-squares mean [95% CI]) with sparsentan+SGLT2i (-11.1% [-26.3% to 7.3%]) vs sparsentan alone (17.7% [-2.4% to 42.1%]) (ratio [95% CI], 0.75 [0.58 to 0.98]; P<0.05). Few treatment-related adverse events were severe or serious or led to discontinuation. CONCLUSION: In patients with IgAN, replacing RASi with sparsentan while on stable SGLT2i resulted in marked reductions in albuminuria. Adding SGLT2i to stable sparsentan resulted in modest further reductions in proteinuria. Sparsentan combined with SGLT2i was well tolerated, with no unexpected safety signals.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.