In 2020, the International Society of Nephrology agreed a consensus definition of clinical trial outcomes for kidney failure (Levin et al, 2020). The present retrospective cohort study sought to compare renal outcomes of SGLT2 inhibitors and DPP-4 inhibitors in people with type 2 diabetes according to these criteria. Using data from the UK Clinical Practice Research Database, 23,438 people initiating an SGLT2i were compared with those initiating a DPP-4i, matched 1:1 according to propensity score (factors including age, sex, frailty, and micro- and macrovascular complications).
The primary endpoint was a composite of ≥40% eGFR decline (confirmed by a second measurement over 28 days), end-stage renal disease (ESRD; itself a composite of kidney transplantation, maintenance of dialysis, sustained low eGFR <15 mL/min/1.73 m² or diagnosis of ESKD) or renal death. Over a median follow-up of 2.1 years, use of an SGLT2i was associated with a lower risk of the primary endpoint compared with a DPP-4i (7.5 vs 11.8 events per 1000 person-years; hazard ratio [HR], 0.64; 95% CI, 0.56–0.74).
Regarding individual outcomes, SGLT2i use was associated with reduced risk of all-cause mortality, eGFR decline and ESRD. A difference in all-cause mortality rates was only observed in people with a lower HbA1c (<53 mmol/mol) at baseline, whereas differences in renal outcomes appeared to be independent of glycaemic control.
Despite limitations, including the retrospective cohort design and potential selection bias due to the use of propensity scores, the authors conclude that SGLT2is are associated with a reduced risk of kidney disease progression and death compared with DPP-4is.
The study was funded by AstraZeneca.
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