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SGLT2 inhibitors reduce kidney-failure risk in type 2 diabetes

September 11, 2019

By Will Boggs MD

NEW YORK (Reuters Health) - Using SGLT2 inhibitors significantly cuts the risk of kidney failure and acute kidney injury in patients with type 2 diabetes, according to a systematic review and meta-analysis.

Several trials have suggested protection against acute kidney injury and declining estimated glomerular filtration rate (eGFR) with the use of SGLT2 inhibitors. But it remains unclear whether the drugs protect against kidney failure across different levels of kidney function and albuminuria in people with type 2 diabetes.

Dr. Meg J. Jardine of the University of New South Wales, in Sydney, Australia, and colleagues assessed the effects of SGLT2 inhibitors on major kidney outcomes in patients with type 2 diabetes in their systematic review and meta-analysis of four randomized trials that included more than 38,000 participants from six continents.

Compared with placebo, SGLT2-inhibitor treatment produced a 33% reduction in the risk of the composite outcome of dialysis, transplantation, or death due to kidney disease (P=0.0019), the researchers report in The Lancet, online September 5.

SGLT2 inhibitor treatment was also associated with a 35% reduced risk of end-stage kidney disease; a 42% lower risk of substantial loss of kidney function, end-stage kidney disease, or death due to kidney disease; and a 25% lower risk of acute kidney injury, compared with placebo.

There was clear and significant evidence of benefit across all eGFR subgroups, including those with a baseline eGFR below 45 mL/min/1.73 m2. And there was no evidence of differences in treatment effect for the composite outcome across urinary albumin-to-creatinine ratio (UACR) subgroups or between users and nonusers of RAS blockade-based treatments at baseline.

"These data provide substantive evidence supporting the use of SGLT2 inhibitors to prevent clinically important kidney outcomes in individuals with type 2 diabetes," the researchers conclude.

"Overall, the findings from (this) 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)," writes Dr. Richard E. Gilbert of St. Michael's Hospital in Toronto, Canada, in a linked editorial.

"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," he concluded.

Dr. Aaron Y. Kluger from Baylor Heart and Vascular Institute, in Dallas, Texas, who recently reviewed the effects of SGLT2 inhibitors on cardiorenal outcomes, told Reuters Health by email, "In addition to treating diabetes and reducing cardiovascular events, SGLT2 inhibitors have demonstrable benefits on renal outcomes - even on top of the protective effects imparted by RAAS inhibitors. If we extrapolate from these data, an average patient with diabetic chronic kidney disease (CKD) may forestall the need for dialysis by years or eliminate that risk completely by early initiation of SGLT2 inhibitors."

"Clinicians should strongly consider SGLT2 inhibitors for treatment of type 2 diabetes patients at risk of worsening renal disease," said Dr. Kluger, who was not involved in the new work. "This holds true even for those with eGFR lower than 45 mL/min, regardless of the fact that SGLT2 inhibitors are not generally approved in patients with reduced renal filtration function."

"This is a very exciting time in the fields of endocrinology, cardiology, and nephrology, because SGLT2 inhibitors influence each of these specialties," he said. "This is especially true now that the DAPA-HF (the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial) results suggest that these drugs may have applications in heart failure independent of patient diabetes status."

"We look forward to efforts in the public and private sectors to improve access to these important medications, since the prevalence pools of patients with type 2 diabetes, heart failure, and CKD are expanding," he added. "Patients need these medications now, and many fear that by the time SGLT2 inhibitors are practically available to underinsured and cash-paying patients, it may be too late."

The study had no external funding. All except one of the study authors report ties to manufacturers of SGLT-2 inhibitors, as does Dr. Gilbert.

Dr. Jardine did not respond to a request for comments.


Lancet 2019.

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