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Diabetes and Effects of SGLT2 Inhibitors on Kidney Outcomes
Quick Takes
- SGLT2 inhibitors safely reduce the risk of kidney disease progression, acute kidney injury, cardiovascular death, and hospitalization for heart failure in patients with chronic kidney disease or heart failure, irrespective of diabetes status.
- The proportional benefits were similar in patients with and without diabetes and appeared to be evident across the wide range of kidney function studied.
- These data support a central role for SGLT2 inhibitors as a disease-modifying therapy for chronic kidney disease, irrespective of diabetes status, primary kidney diagnosis, or level of kidney function.
Study Questions:
What are the effects of sodium glucose co-transporter-2 (SGLT2) inhibitors on kidney disease progression according to a standardized outcome definition, and on acute kidney injury, death, heart failure, and key safety outcomes by diabetes status?
Methods:
The investigators identified 13 trials involving 90,413 participants. After exclusion of four participants with uncertain diabetes status, they analyzed 90,409 participants (74,804 [82.7%] participants with diabetes [>99% with type 2 diabetes] and 15,605 [17.3%] without diabetes; trial-level mean baseline estimated glomerular filtration rate [eGFR] range 37–85 mL/min per 1.73 m2). The main focus of efficacy analyses was on kidney disease progression, acute kidney injury, and a composite of cardiovascular death or hospitalization for heart failure. Kidney disease progression was defined as a sustained eGFR decrease (≥50%) from randomization, end-stage kidney disease (i.e., start of maintenance dialysis or receipt of a kidney transplant), a sustained low eGFR (<15 mL/min per 1.73 m2 or <10 mL/min per 1.73 m2) or death from kidney failure. Inverse-variance-weighted averages of log hazard ratios or log relative risks (RRs) were then used to estimate the treatment effects, summarized as RR (95% confidence interval [CI]), in each patient group and overall.
Results:
Compared with placebo, allocation to an SGLT2 inhibitor reduced the risk of kidney disease progression by 37% (RR, 0.63; 95% CI, 0.58–0.69) with similar RRs in patients with and without diabetes. In the four chronic kidney disease trials, RRs were similar irrespective of primary kidney diagnosis. SGLT2 inhibitors reduced the risk of acute kidney injury by 23% (RR, 0.77; 95% CI, 0.70–0.84) and the risk of cardiovascular death or hospitalization for heart failure by 23% (RR, 0.77; 95% CI, 0.74–0.81), again with similar effects in those with and without diabetes. SGLT2 inhibitors also reduced the risk of cardiovascular death (RR, 0.86; 95% CI, 0.81–0.92) but did not significantly reduce the risk of noncardiovascular death (RR, 0.94; 95% CI, 0.88–1.02). For these mortality outcomes, RRs were similar in patients with and without diabetes. For all outcomes, results were broadly similar irrespective of trial mean baseline eGFR. Based on estimates of absolute effects, the absolute benefits of SGLT2 inhibition outweighed any serious hazards of ketoacidosis or amputation.
Conclusions:
The authors concluded that randomized data support SGLT2 inhibitor use for modifying risk of kidney disease progression and acute kidney injury, not only in patients with type 2 diabetes at high cardiovascular risk, but also in patients with chronic kidney disease or heart failure irrespective of diabetes status, primary kidney disease, or kidney function.
Perspective:
This meta-analysis of the available large placebo-controlled SGLT2 inhibitor trials shows that SGLT2 inhibitors safely reduce the risk of kidney disease progression, acute kidney injury, cardiovascular death, and hospitalization for heart failure in patients with chronic kidney disease or heart failure, irrespective of diabetes status. Furthermore, the proportional benefits were similar in patients with and without diabetes and appeared to be evident across the wide range of kidney function studied. Overall, these data support a central role for SGLT2 inhibitors as a disease-modifying therapy for chronic kidney disease, irrespective of diabetes status, primary kidney diagnosis, or level of kidney function.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure
Keywords: Acute Kidney Injury, Amputation, Diabetes Mellitus, Type 2, Disease Progression, Glomerular Filtration Rate, Heart Disease Risk Factors, Heart Failure, Ketosis, Kidney Failure, Chronic, Kidney Transplantation, Metabolic Syndrome, Primary Prevention, Renal Insufficiency, Chronic, Risk Factors, Sodium-Glucose Transporter 2, Sodium-Glucose Transporter 2 Inhibitors
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