Among patients without type 2 diabetes (T2D) with high cardiovascular disease (CVD) risk, chronic kidney disease (CKD), and/or heart failure (HF), a systematic review and meta-analysis found CV and mortality benefits from sodium-glucose co-transporter-2 (SGLT2) inhibitor use. These findings were published in The Lancet.
Collaborators from the Nuffield Department of Population Health Renal Studies Group and the SMART-C (SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium) searched publication databases through September 2022 for double-blind, placebo-controlled trials evaluating the safety and efficacy of SGLT2 inhibitors.
A total of 13 large trials were included in this analysis. The pooled study population comprised 90,413 patients, among whom 35.7% were women and average ages ranged from 61.9 to 71.8 years. The trial populations had T2D with high risk for atherosclerotic CVD (n=42,568), CKD (n=25,898), and HF (n=21,947). Among the CKD and HF cohorts, 20,931 and 11,305 had diabetes, respectively.
For the outcome of kidney disease progression, SGLT2 inhibitors were favored over placebo among patients with diabetes (relative risk [RR], 0.62), patients without diabetes (RR, 0.69), and overall (RR, 0.63). Similarly, SGLT2 inhibitors were favored over placebo for the outcome of acute kidney injury among patients with diabetes (RR, 0.79), patients without diabetes (RR, 0.66), and overall (RR, 0.77).
Treatment with SGLT2 inhibitors was also favored over placebo for kidney disease progression among patients with diabetic kidney disease or nephropathy (RR, 0.60), glomerular disease (RR, 0.60), or any diagnosis (RR, 0.62). However, the results were not significant among patients diagnosed with ischemic and hypertensive kidney disease (RR, 0.70; 95% CI, 0.50-1.00) or other kidney disease or unknown (RR, 0.74; 95% CI, 0.51-1.08).
For CV outcomes, SGLT2 inhibitors were favored for reducing CV death or HF hospitalization among patients with diabetes (RR, 0.77), no diabetes (RR, 0.79), or overall (RR, 0.77) and CV death among patients with diabetes (RR, 0.86) and overall (RR, 0.86) but not among patients without diabetes (RR, 0.88; 95% CI, 0.78-1.01) compared with placebo.
All-cause mortality risk was decreased with SGLT2 inhibitor use compared with placebo among patients with diabetes (RR, 0.88) and overall (RR, 0.89) but not for those without diabetes (RR, 0.93; 95% CI, 0.84-1.03).
Use of SGLT2 inhibitors was not favored over placebo for reducing risk for non-CV mortality.
Placebo was favored over SGLT2 inhibitors for the outcome of ketoacidosis (RR, 2.12) and lower limb amputation (RR, 1.15) among patients with diabetes.
A limitation of this study is the low number of CV death and HF hospitalization events among patients with CKD without diabetes.
“SGLT2 inhibitors safely reduce the risk of kidney disease progression, acute kidney injury, cardiovascular death, and hospitalisation for heart failure in patients with chronic kidney disease or heart failure, irrespective of diabetes status,” the study authors wrote. “The proportional benefits were similar in patients with and without diabetes and appeared to be evident across the wide range of kidney function studied.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Nuffield Department of Population Health Renal Studies Group, SMART-C. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. Published online November 6, 2022. doi:10.1016/S0140-6736(22)02074-8