Meta-analysis supports use of SGLT2 inhibitors to prevent kidney failure
medwireNews: Findings from a systematic review and meta-analysis suggest that sodium-glucose cotransporter (SGLT)2 inhibitors reduce the risk for major adverse kidney outcomes among people with type 2 diabetes, regardless of baseline kidney function.
“Our findings provide the strongest evidence yet that SGLT2 inhibition should be routinely offered to individuals with type 2 diabetes at risk of progressive kidney disease,” write the study authors in The Lancet Diabetes & Endocrinology.
Meg Jardine, from The George Institute for Global Health in Newtown, New South Wales, Australia, and colleagues analyzed data from four randomized placebo-controlled trials of three SGLT2 inhibitors: EMPA-REG OUTCOME (empagliflozin); CANVAS Program (canagliflozin); CREDENCE (canagliflozin); and DECLARE–TIMI 58 (dapagliflozin).
The studies involved a total of 38,723 participants (35.0% female) with the average age ranging from 63.0 to 63.9 years, while the proportion of patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73m2 ranged from 7.4% in DECLARE-TIMI to 58.9% in CREDENCE. In all, 252 patients experienced the composite renal endpoint of transplantation, dialysis or death due to kidney disease.
Jardine et al found that participants treated with SGLT2 inhibitors had a significant 33% reduction in the risk for the composite endpoint compared with those given placebo, with consistent benefit seen across the four trials.
The researchers identified “some evidence that the magnitude of benefit might be attenuated across progressively lower eGFR subgroups,” but stress that there was “clear, separately significant evidence of benefit” associated with SGLT2 inhibitor treatment among participants from all kidney function categories.
Specifically, among individuals with eGFR of 90 mL/min per 1.73m2, SGLT2 inhibitors were associated with a 63% reduction in the risk for the composite renal endpoint relative to placebo. The risk reductions among those with eGFR of 60 to <90, 45 to<60, and less than 45 mL/min per 1.73m2 were 40%, 45%, and 30%, respectively.
“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,” says the team.
Writing in an accompanying comment, Richard Gilbert (University of Toronto, Ontario, Canada) says that the findings of the meta-analysis “strongly support the notion that SGLT2 inhibitors offer kidney protection to a broad range of patients with type 2 diabetes, including those with both preserved and low eGFR, ostensibly independent of any glucose-lowering effect (which will probably be minimal in patients with low eGFR).”
He believes that “[a]fter 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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