Results
As for efficacy outcomes, Jorge et al. examined the following:
- Renal progression, defined as a decrease in estimated glomerular filtration rate (eGFR) by less than or equal to 30%, or new ESRD
- MACE, defined as ischemic stroke, myocardial infarction, venous thrombosis, cardiovascular death or heart failure.
Regarding safety outcomes, they examined genital infections (e.g., candidiasis), because these are a known potential side effect of SGLT2i, and serious infections (e.g., pyelonephritis).
For patients with SLE, SGLT2i was associated with lower risk of MACE (HR 0.69, 95% CI 0.48–0.99) and renal progression (HR 0.71, 95% CI 0.52–0.98) than DPP4i use.
“This translates to an absolute risk reduction (ARR) of 4.1 MACE events and 4.7 renal progression events per 100 person years in people with SLE,” explained Dr. Jorge.
For patients with SLE and lupus nephritis, there was a larger ARR of 10.2 MACE per 100 person years, but no statistically significant difference in renal progression. “This may be due to the fact that this was a smaller group,” Dr. Jorge noted.
The cumulative incidence of MACE and renal progression over three years of follow-up was also lower in patients who received SGLTi.
As expected, there was an increased risk of genital infection in the SGLT2i group. “Most of these are benign, easily treated yeast infections,” Dr. Jorge explained. There was no increase in the risk of severe infections.
Of note, Dr. Jorge clarified, “Because these patients also had DM2, we cannot necessarily say how much of the component of kidney progression we prevented was related to SLE as opposed to DM2. But I think it’s really important that this is some of first real-world data we have in patients with SLE. We definitely need more data.”
Are we now beyond needing randomized controlled trials?
An audience member asked about the need for RCTs now that the target trial emulation framework is available.
Dr. Jorge responded, “I think there is definitely a role for RCTs. A limitation of this study is that the patients also had to have DM2. An RCT would be needed to study this medication in people without another indication for SGLT2i. Also, the target trial emulation framework is most useful when comparing two different treatment options. It’s a bit more difficult to emulate a placebo-controlled trial. The benefit here is that you can compare the effectiveness of treatment in populations who would otherwise be excluded from RCTs.”
