Sodium-glucose cotransporter-2 (SGLT2) inhibitors lower the risk of dialysis and other clinically important kidney outcomes in patients with type 2 diabetes, concludes a systematic review and meta-analysis in The Lancet Diabetes & Endocrinology.
The review identified four randomized controlled trials of SGLT2 inhibitors that reported data on major kidney outcomes in patients with type 2 diabetes. The EMPA-REG OUTCOME trial evaluated empa-gliflozin in 7020 patients; the CANVAS Program and CREDENCE trial evaluated canagliflozin in 10,142 and 4401 patients, respectively; and the DECLARE-TIMI 58 trial evaluated dapagliflozin in 17,160 patients. The CREDENCE study was designed as an event-driven kidney outcome trial; the other three studies were cardiovascular outcome trials.
Meta-analysis included data on 38,723 patients, mean age 63.0 to 63.9 years and 65% male. Percentage of patients with chronic kidney disease (estimated glomerular filtration rate [eGFR] less than 60 mL/min/1.73 m2) ranged from 7.4% in the DECLARE-TIMI 58 trial to 59.9% in CREDENCE. The primary outcome of dialysis, transplantation, or death due to kidney disease occurred in 252 patients. Incident kidney failure occurred in 335 patients and acute kidney injury (AKI) in 943.
Treatment with an SGLT2 inhibitor was associated with a one-third reduction in the risk of the primary outcome: relative risk (RR) 0.67, compared to placebo. Patients receiving SGLT2 inhibitors were also at lower risk of kidney failure, RR 0.65; and AKI, RR 0.75. All of these effects were consistent across studies.
Some data suggested that the benefit of SGLT2 inhibitors might be reduced at lower levels of eGFR. However, there was significant benefit in all eGFR subgroups; for patients with a baseline eGFR of 30 to 45 mL/min/1.73 m2, the RR was 0.70.
The reduction in adverse kidney outcomes with SGLT2 inhibitors was similar for subgroups defined by baseline albuminuria and use of renin-angiotensin system inhibitors. Effects on long-term eGFR slope varied, with the greatest placebo-subtracted difference observed in the CREDENCE trial: 2.74 mL/min/1.73 m2 per year.
Cardiovascular outcome trials have reported promising effects of SGLT2 inhibitors on kidney outcomes. However, there are limited data on their effects in patients at high risk of patient-level kidney outcomes.
This meta-analysis of more than 38,000 patients with type 2 diabetes finds significant reductions in dialysis, transplantation, or death due to kidney disease with SGLT2 inhibitor therapy [Neuen BL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2019; DOI: 10.1016/S2213-8587(19)30256-6].