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The impact of SGLT2-inhibitor on SLE outcomes

Systemic lupus erythematosus (SLE) is associated with increased risk of cardiovascular events due to both traditional and disease-specific risk factors. Since chronic kidney disease (CKD) is one of the strongest CV risk factors, any new strategy to reduce proteinuria and avoid a decline in renal function may likely improve patient outcomes. In large cardiovascular outcome trials, the use of a fairly new-kid-on-the-block therapy, sodium–glucose cotransporter-2 inhibitors (SGLT2i) appear to be both cardio and renal-protective. Examples of SGLT2i include dapagliflozin and empagliflozin. Would the use of SGLT2i have the same impact in SLE?

Dr Jorge (Abstract# 1579) used a large US multi-centre electronic health record-based and used a technique called target trial emulation to mimic data from RCTs. They compared outcomes between SGLT2i vs a comparator oral hypoglycaemic agent, dipeptidyl peptidase 4 inhibitors (DPP4-i; examples include sitagliptin and linagliptin) in SLE patients, with or without lupus nephritis (LN). Using propensity match scoring, the data showed the use of SGLT2-i vs DPP4-i (for non-SLE indication) was associated with reduced risk of major cardiovascular events (MACE; HR: 0.69) and renal progression (as defined by worsening of eGFR by 30% or progression to end-stage renal disease (ESRD; HR:0.71). Similar finding and/or trend were observed in patients with LN. Genital infection was associated with the use of SGLT2i.

Dr Lo (Abstract# 0590) used the same study design and comparator as above but used a different population, SLE patients with type 2 diabetes. They found that SGLT2i vs DPP4i use was associated with significantly reduced risks of developing acute kidney injury, CKD, ESRD, hospitalisation, and heart failure. There was no difference in mortality between the two groups. 

Both studies supported the use of SGLT2i in the prevention of MACE and ESRD in SLE. Safety profile also appears to be safe. This will need to be investigated in definitive studies. It would also be interesting to see how much added benefit this strategy confers, on top of the routine use of renin-angiotensin-aldosterone system (RAAS) inhibitors in LN.


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