Safety and efficacy of the SGLT2 inhibitor dapagliflozin in patients with systemic lupus erythematosus: a phase I/II trial

Abstract

Objective: Sodium-glucose cotransporter-2 inhibitors have been identified profound renal/cardiac protective effects in different diseases. Here, we assessed the safety and efficacy of dapagliflozin among adult patients with systemic lupus erythematosus (SLE).

Methods: We conducted a single-arm, open-label, investigator-initiated phase I/II trial of dapagliflozin in Chinese patients with SLE with/without lupus nephritis (LN). Patients received oral dapagliflozin at a daily dose of 10 mg added to the standard of care for 6 months. The primary end point was the safety profile. The secondary efficacy end points were composite assessments of disease activity.

Results: A total of 38 eligible patients were enrolled. Overall, 19 (50%) adverse events (AEs) were recorded, including 8 (21%) AEs leading to drug discontinuation, of which 4 (10.5%) were attributed to dapagliflozin. Two serious AEs (one of major lupus flare and one of fungal pneumonia) were recorded. Lower urinary tract infection was observed in one (2.63%) patient. The secondary end points revealed no improvement of SLE Disease Activity Index scores or proteinuria (among 17 patients with LN); the cumulative lupus flare rate was 18%, and a reduction of ~30% in the prednisone dose was captured. Net changes in body mass index (-0.50 kg/m²), systolic blood pressure (-3.94 mm Hg) and haemoglobin levels (+8.26 g/L) were detected. The overall estimated glomerular filtration rate (eGFR) was stable, and there was an improvement in the eGFR slope among patients with LN with a baseline eGFR <90 mL/min/1.73 m².

Conclusion: Dapagliflozin had an acceptable safety profile in adult patients with SLE. Its possible renal/cardiac protective effects and long-term safety issues in patients with SLE, patients with LN in particular, call for further exploration.

Trial registration number: ChiCTR1800015030.

Keywords: lupus erythematosus, systemic; lupus nephritis; outcome and process assessment, health care.

Figure 1

Trial profile. SGLT2i, sodium-glucose cotransporter-2 inhibitor.

Figure 2

Secondary efficacy outcomes. (A–C) Changes of SLEDAI-2K scores (A), daily dosage (B) and percentage of prednisone (C) from baseline to 6 months. T-bars indicate SE. (D) Changes of median 24-hour urinary protein, T-bars indicate 25th–75th percentile. SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; UPRO, urine protein. *P<0.05, **p<0.001, ***p<0.0001.

Figure 3

Exploratory outcomes. (A–D) Changes in body mass index (BMI) (A), systolic blood pressure (BP) (B), haemoglobin (C) and estimated glomerular filtration rate (eGFR) (D) from baseline to 6 months. The black lines represent all patients, the red lines represent the LN group and the blue lines represent the non-LN group. Nominal p values were provided only for black lines. *P<0.05, **p<0.001. (E) Mean 6-month eGFR slopes were presented among all patients (n=38), patients with LN (n=17) and patients without LN (n=21). (F) The mean 6-month eGFR slopes in patients with LN with a baseline eGFR value ≥90 (n=13) and <90 mL/min/1.73 m² (n=4) were presented.