Sodium-glucose cotransporter 2 (SGLT2) inhibition and autoimmunity

Abstract

The approval of sodium-glucose cotransporter (SGLT2) inhibitors has revolutionized the management of patients with diabetes, heart failure and especially those with chronic kidney disease (CKD). Beyond development of CKD, patients with autoimmune disorders have an increased cardiovascular morbidity and mortality. Therefore, this patient population would benefit the most from effective therapies to reduce this burden, and secondly, slowing of CKD progression to reduce the frequency of kidney failure. Patients with systemic autoimmune disorders, such as systemic lupus erythematosus with lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis were excluded from the DAPA-CKD trial, and higher doses of glucocorticoids or intravenous use of immunosuppression within 3 months were exclusion criteria of the EMPA-KIDNEY trial. Thus, these agents remain untested in patients with active autoimmune kidney diseases in a systematic way, and this gap is unlikely to be filled by high-quality randomized clinical trials. Beyond having nephro- and cardioprotective effects, SGLT2i have shown in vivo and in vitro efficacy to manage autoimmunity in SLE, LN and rheumatoid arthritis (RA). These effects need to be confirmed in humans, but might provide a further rationale for the use of these potent drugs. The safety profile is in general favourable, but “sick day rules” need to be followed in order to avoid serious side effects.