Impact of diabetes on the effects of SGLT2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials
In a collaborative meta-analysis of large placebo-controlled trials, SGLT2 inhibitors reduced kidney disease progression by about 37% with similar relative benefits in patients with and without diabetes, supporting their use across the spectrum of CKD irrespective of diabetes status.
Background
SGLT2 inhibitors reduce adverse kidney and cardiovascular outcomes in patients with heart failure, chronic kidney disease, or type 2 diabetes at high cardiovascular risk. However, none of the trials enrolling patients with and without diabetes were individually designed to assess outcomes separately in the non-diabetic subgroup, leaving uncertainty about whether benefits depend on diabetes status.
Study design
The investigators performed a systematic review and meta-analysis of large, double-blind, placebo-controlled SGLT2 inhibitor trials (at least 500 participants per group and at least 6 months in duration) using inverse-variance-weighted analysis. Thirteen trials involving 90,409 participants were analysed, of whom 82.7% had diabetes (more than 99% type 2) and 17.3% did not.
Key findings
Compared with placebo, SGLT2 inhibitors reduced kidney disease progression by 37% (relative risk 0.63, 95% CI 0.58-0.69), with similar relative risks in patients with and without diabetes and irrespective of primary kidney diagnosis. They also reduced acute kidney injury by 23% (0.77, 0.70-0.84) and cardiovascular death or heart failure hospitalisation by 23% (0.77, 0.74-0.81), again with comparable effects regardless of diabetes status, and reduced cardiovascular death (0.86, 0.81-0.92). Results were broadly consistent across baseline eGFR ranges.
Clinical implications
The absolute benefits of SGLT2 inhibition outweighed serious hazards such as ketoacidosis or amputation. The data support using SGLT2 inhibitors to modify the risk of kidney disease progression and acute kidney injury not only in patients with type 2 diabetes at high cardiovascular risk, but also in those with chronic kidney disease or heart failure regardless of diabetes status, primary kidney disease, or kidney function.
Category
Research
Source
The Lancet
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