Sodium-glucose co-transporter-2 (SGLT2) inhibitors can prevent kidney failure in patients with type 2 diabetes across most estimated glomerular filtration rate (eGFR) and albuminuria subgroups, according to the authors of a new systematic review and meta-analysis published in the Lancet Diabetes and Endocrinology.

Meg Jardine, MBBS, PhD, of The George Institute for Global Health in Australia, and colleagues pooled results from 4 major trials of 3 SGLT2 inhibitors: empagliflozin (EMPA-REG OUTCOME), canagliflozin (CANVAS Program and CREDENCE), and dapagliflozin (DECLARE–TIMI 58). Of 38,723 total patients with type 2 diabetes, 252 required dialysis or transplantation or died of kidney disease, 335 developed end-stage renal disease (ESRD), and 943 had acute kidney injury (AKI).

Use of SGLT2 inhibitors significantly cut the risk for the primary composite end point of dialysis, transplantation, or death from kidney disease by 33% with, consistent benefit observed across the trials. SGLT2 inhibitors also consistently and significantly reduced the risks of ESRD and AKI by 35% and 25%, respectively, allaying earlier concerns that SGLT2 inhibitors increase AKI risk.

Previous research suggested that the efficacy of SGLT2 inhibitors lessens with declining kidney function, but there was “clear, separate evidence of benefit” for patients of almost all eGFR groups in this meta-analysis, including those with low baseline eGFR of 30 to 45 mL/min/1.73 m² (for whom SGLT2 inhibitors have not been recommended), who had a significant 30% reduction in risk for substantial loss of kidney function, ESRD, or death from kidney disease. The investigators found no significant difference in these outcomes across albuminuria subgroups or between users and nonusers of renin-angiotensin system blockade.

Along with lowering glucose, SGLT2 inhibitors reduce blood pressure, weight, and albuminuria and might have direct hemodynamic effects on the kidney, the reviewers noted.

“To the best of our knowledge, these results provide the strongest evidence yet that SGLT2 inhibitors should be routinely offered to individuals with type 2 diabetes at risk of progressive kidney disease,” Dr Jardine’s team stated. “The clear evidence of renoprotection across the spectrum of kidney function studied to date calls into question the existing restrictions on the use of SGLT2 inhibitors in people with reduced kidney function and suggests that many more individuals with type 2 diabetes at high risk of kidney failure are likely to benefit from treatment with these drugs.”

In an accompanying editorial, Richard E Gilbert, MD, of St Michael’s Hospital in Toronto, commented, “After years of stagnation, we are now on the brink of a new paradigm in the prevention and treatment of kidney disease in people with type 2 diabetes.”

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References

Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis [published online September 5, 2019]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(19)30256-6

Gilbert RE. Diabetic kidney disease 2.0: the treatment paradigm shifts [published online September 5, 2019]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(19)30253-0