Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials
Pooling 11 trials in more than 85,000 patients, GLP-1 receptor agonists reduced clinically important kidney failure events as well as heart attacks, strokes, and death in people with type 2 diabetes.
Study design
The investigators searched MEDLINE, Embase, and the Cochrane Central Register through March 2024 for randomized placebo-controlled trials of at least 500 participants with type 2 diabetes, at least 12 months of follow-up, and a primary clinical kidney or cardiovascular outcome. The SELECT trial (cardiovascular disease and obesity without diabetes) was added post hoc, yielding 11 trials and 85,373 participants analysed with a random-effects model.
Key findings
Among participants with type 2 diabetes, GLP-1 receptor agonists reduced the composite kidney outcome (kidney failure, sustained 50% eGFR decline, or kidney death) by 18% (HR 0.82, 95% CI 0.73-0.93), kidney failure by 16% (HR 0.84), major adverse cardiovascular events by 13% (HR 0.87), and all-cause death by 12% (HR 0.88). Results were essentially unchanged when the SELECT trial was included.
Safety
There was no difference in serious adverse events, including acute pancreatitis and severe hypoglycaemia, between GLP-1 receptor agonist and placebo groups. However, treatment discontinuation due to adverse events was more frequent with GLP-1 receptor agonists (RR 1.51, 95% CI 1.18-1.94).
Clinical implications
The findings establish that GLP-1 receptor agonists meaningfully reduce clinically important kidney events, not just albuminuria, reinforcing their role in the modern multidrug approach to diabetic kidney disease alongside renin-angiotensin blockade, SGLT2 inhibitors, and finerenone.
Category
Research
Source
The Lancet Diabetes & Endocrinology
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