Dapagliflozin, an oral sodium-glucose co-transporter 2 (SGLT2) inhibitor originally developed for the treatment of type 2 diabetes, significantly reduced residual proteinuria in patients with inactive lupus nephritis (LN) when added to standard-of-care therapy, without raising major safety concerns, according to a randomised crossover trial published in Nephrology Dialysis Transplantation.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated renal benefits in several kidney diseases, but patients with lupus nephritis receiving immunosuppressive therapy have generally been excluded from major SGLT2 inhibitor trials. The investigators therefore evaluated the efficacy and safety of dapagliflozin specifically in patients with inactive LN who continued to have residual proteinuria despite standard treatment. The trial enrolled adults with class III or IV lupus nephritis, with or without class V disease, who had no evidence of active disease, proteinuria exceeding 500 mg/24 hours, and an estimated glomerular filtration rate (eGFR) of at least 20 mL/min. Participants were receiving stable renin–angiotensin–aldosterone system inhibitor therapy and mycophenolate mofetil at doses of up to 2 g/day.
Participants were randomly assigned to receive dapagliflozin in addition to standard-of-care therapy or standard-of-care therapy alone for six months, after which the groups crossed over. The primary endpoint was the change in proteinuria from baseline at six and 12 months. Of 97 patients screened, 67 were excluded because of active LN, insufficient proteinuria, or low eGFR. Thirty patients were ultimately randomised, with 14 initially receiving dapagliflozin and 16 continuing standard-of-care therapy alone. Nine patients were subsequently excluded from the analysis because of new LN flares or loss to follow-up. The mean age of participants was 40.6 ± 12.3 years, and 19 patients (90.5%) were women. None of the participants had diabetes, and the mean body mass index was 26.1 ± 5.2 kg/m².
After six months, dapagliflozin was associated with a 36.1% reduction in proteinuria, compared with a 3.5% reduction with standard-of-care therapy alone, with the difference reaching statistical significance (P = 0.03). Hypotension-related symptoms were reported more frequently with dapagliflozin, occurring in seven patients (33.3%). However, none discontinued treatment because of these symptoms, and no significant differences in blood pressure or body weight were observed between the treatment groups during follow-up. One urinary tract infection was reported in each treatment group; both episodes occurred in the same patient following crossover. The investigators concluded that adding dapagliflozin to standard therapy resulted in a significant reduction in residual proteinuria in patients with inactive LN without major safety concerns in the study population.
Evidence from another randomized trial has been more cautious. Mohamed et al. evaluated the renal and hematological effects, efficacy, and safety of dapagliflozin as adjunctive therapy in patients with LN. In the double-blind, placebo-controlled trial, 79 adults with biopsy-proven LN and an eGFR above 30 mL/min/1.73 m² were randomised to receive dapagliflozin 10 mg/day (n = 38) or placebo (n = 41) for 12 months alongside standard immunosuppressive therapy. The primary renal endpoint was the percentage change in 24-hour urinary protein excretion, while secondary outcomes included changes in eGFR and haematological parameters, including haemoglobin, erythropoietin, hepcidin, ferritin, and transferrin saturation.
At 12 months, dapagliflozin was associated with a numerical reduction in proteinuria compared with placebo, but the difference was not statistically significant. Adjusted analyses using analysis of covariance also found no significant treatment effect. There were likewise no significant differences between groups in eGFR, eGFR slope, or the assessed haematological parameters. These findings suggest that dapagliflozin may have a role in reducing residual proteinuria in selected patients with lupus nephritis, particularly those with inactive disease and persistent proteinuria despite standard therapy. However, the evidence remains limited, and larger, adequately powered trials with longer follow-up are needed to establish its efficacy, safety, and appropriate place in the management of lupus nephritis.
References
- Vajgel G, Júnior BMDS, Filho CRSM, de Oliveira CBL, Costa DMDN, de Lima CAD, Valente LM, Sandrin-Garcia P. Efficacy and safety of dapagliflozin in inactive lupus nephritis: a randomized crossover trial. Nephrol Dial Transplant. 2026 Jun 30;41(7):1253-1261.
- Mohamed N, Zayed KN, Elhadedy MA, Badawi MH, Mortada WI, Nabieh KA, Sobh MA, Refaie AF. Dapagliflozin in lupus nephritis: renal and hematologic outcomes from a randomized controlled trial. Clin Kidney J. 2026 Jul 10;19(8):sfag231.