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01-11-2022 | Systemic lupus erythematosus | News

Dapagliflozin may warrant further investigation for SLE

Author: Claire Barnard


medwireNews: The sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin deserves further study as an add-on therapy for reducing renal and cardiovascular (CV) risk in patients with systemic lupus erythematosus (SLE), suggest preliminary trial findings.

Discussing the rationale for their phase 1/2 trial, Shuang Ye (Shanghai Jiaotong University, China) and team explain that SGLT2 inhibitors – a class of agents used for the treatment of type 2 diabetes – work by lowering “glucose reabsorption in the epithelial cells of the proximal renal tubule of the kidney, which results in decreased blood glucose and glycated haemoglobin levels,” leading to an improvement in renal and CV outcomes.

They add that “SGLT2 [inhibitors] might further contribute to reducing inflammation, modulating endothelial dysfunction and decelerating atherosclerosis, which are all relevant to the pathophysiology of SLE.”

Therefore, “[w]ith all the beneficial properties of SGLT2 [inhibitors], they have become appealing candidates for treating patients with SLE, especially those with lupus nephritis (LN),” say Ye and team.

The investigator-initiated phase 1/2 trial included 38 patients with SLE (mean age 35 years, 95% women) who were given dapagliflozin 10 mg/day in addition to ongoing standard-of-care treatment, most commonly with hydroxychloroquine (87%). The average SLE duration was 8 years, 45% of participants had active LN, and 13% had a history of diabetes.

Ye et al report that add-on dapagliflozin “had an acceptable safety profile” during the 6-month trial period. Half of the participants experienced adverse events (AEs), while 21% experienced AEs leading to treatment discontinuation. The most frequently reported AEs were SLE flares (18%), followed by asymptomatic pyuria (13%) and infections (11%). One patient experienced a urinary tract infection and there were no cases of diabetic ketoacidosis. There were two serious AEs, namely one case of fungal pneumonia and one major disease flare, both of which required hospital admission.

In the efficacy analysis, the team found that the average SLEDAI score decreased nonsignificantly from 4.24 points at baseline to 3.97 points at 6 months, with similar results seen in patients who had LN. The average daily dose of prednisolone decreased significantly during this period, from 14.21 to 10.67 mg, which the researchers say is “compatible with standard-of-care tapering.”

They write in RMD Open that “the potential cardiac/renal protective effects [of dapagliflozin] are still inconclusive” in people with SLE, but note that exploratory analyses suggested a potential beneficial impact on CV risk factors. For instance, average BMI decreased from 23.78 kg/m2 at baseline to 23.28 kg/m2 at 6 months, while average systolic blood pressure declined from 121.32 to 115.97 mmHg.

The investigators conclude that “further properly designed larger-scale, placebo-controlled trials” are required to evaluate dapagliflozin in patients with SLE.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

RMD Open 2022; 8: e002686