MOAMEN ABDELFADIL ISMAIL, OHOUD IBRAHIM QADI, RAGHAD OSAMA ALSAEDI, MURAD MOHAMMED ALGHAMDI, FAISAL MUDWIKH BIN ALAWI ALOTAIBI, MARYAM SAAD ALMUTAIRI, ,FATIMAH MOHAMMAD ALODAH, RANEEM TURKI ALNOMARI, SUMAIH SAEED SALEH ALSAEED, FATEN ALI HEFDHALLAH HAKAMI, SALMA ALYAQOUB, ABDULLAH NAWAF ALHARBI, FAISAL SAAD LAJHER
DOI: https://doi.org/Background: IgA nephropathy (IgAN) remains the most common primary glomerulonephritis worldwide, with limited disease-specific therapies. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have emerged as potential renoprotective agents in CKD, but their role in IgAN is less well established.
Objective: To systematically review the efficacy and safety of SGLT2i in adult patients with IgAN, synthesizing evidence from clinical trials, observational studies, mechanistic analyses, and case reports.
Methods: A systematic search of PubMed, Scopus, Web of Science, Embase, and Google Scholar was conducted through August 15, 2025, following PRISMA 2020 guidelines. Eligible studies included adults with biopsy- or clinically confirmed IgAN receiving any SGLT2i. Data extraction included study design, patient characteristics, intervention details, renal and safety outcomes, and risk of bias assessment using Newcastle–Ottawa Scale and Cochrane RoB 2.
Results: Twenty-three studies met inclusion criteria, including randomized controlled trials, retrospective cohorts, prospective observational studies, mechanistic analyses, and case reports. Across designs, SGLT2i consistently reduced proteinuria (mean reduction up to ~40%) and attenuated eGFR decline. Benefits were observed in monotherapy and in combination with other agents such as sparsentan. Safety profiles were acceptable, with transient eGFR dip, mild genitourinary infections, and volume depletion as the most common adverse events. Mechanistic studies and Mendelian randomization analyses support hemodynamic, anti-inflammatory, and podocyte-protective effects.
Conclusions: SGLT2i offer clinically meaningful renoprotection in IgAN, with a favorable safety profile and plausible mechanistic basis. Although IgAN-specific randomized trials remain limited, current evidence supports their proactive integration into individualized treatment plans, with further research needed to define optimal timing, combinations, and patient selection.
