GLP-1s ‘could play an important role’ in slowing kidney, heart disease progression
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Key takeaways:
- Individuals with type 2 diabetes had fewer kidney outcomes, major CV events and death with GLP-1s.
- GLP-1s lowered kidney and CV outcomes in chronic kidney disease or CVD with overweight or obesity.
GLP-1 receptor agonists improved clinical outcomes related to kidney and heart health while lowering mortality rates for individuals with diabetes, chronic kidney disease or preexisting cardiovascular disease with overweight or obesity.
“GLP-1 receptor agonists not only lower blood glucose levels and body weight, but also have kidney-protective and heart-protective benefits,” Sunil V. Badve, MBBS, MD, PhD, FRACP, professorial fellow at The George Institute for Global Health and the University of New South Wales in Sydney, told Healio. “GLP-1 receptor agonists could play an important role in the management of patients with high risk for kidney disease progression and cardiovascular events.”
Badve and colleagues conducted a meta-analysis, published in The Lancet Diabetes & Endocrinology, identifying 11 randomized controlled trials including 85,373 participants with type 2 diabetes published from inception to March 2024. All trials compared GLP-1 receptor agonists with placebo for at least 12 months with reports of a primary clinical kidney or cardiovascular outcome. In a post hoc analysis, researchers also included the SELECT trial consisting of patients without diabetes but with CVD and a BMI of 27 kg/m2 or higher.
The primary kidney outcome was a composite including kidney failure (renal replacement therapy or estimated glomerular filtration rate [eGFR] < 15 mL/min/1.73m2), a sustained reduction in eGFR by at least 50% or kidney failure mortality. The primary CV outcome was major adverse CV events, defined as CV death, nonfatal myocardial infarction or nonfatal stroke.
For the 67,769 participants with type 2 diabetes, compared with placebo, GLP-1 receptor agonists lowered composite kidney outcomes by 18% (HR = 0.82; 95% CI, 0.73-0.93), kidney failure by 16% (HR = 0.84; 95% CI, 0.72-0.99), major adverse CV events by 13% (HR = 0.87; 95% CI, 0.81-0.93) and all-cause mortality by 12% (HR = 0.88; 95% CI, 0.83-0.93).
In the post hoc analysis including the SELECT trial (n = 85,373), researchers observed similar effects on the composite kidney outcome (HR = 0.81; 95% CI, 0.72-0.92), kidney failure (HR = 0.84; 95% CI, 0.72-0.98), major adverse CV events (HR = 0.86; 95% CI, 0.8-0.92) and all-cause mortality (HR = 0.87; 95% CI, 0.82-0.91). In addition, no evidence of heterogeneity was observed between SELECT and the trials including participants with type 2 diabetes.
The GLP-1 receptor agonist and placebo groups demonstrated no difference in risk for serious adverse events including acute pancreatitis and severe hypoglycemia. However, researchers noted that treatment discontinuation caused by adverse events was more frequent among participants in the GLP-1 receptor agonist groups vs. the placebo groups (RR = 1.51; 95% CI, 1.18-1.94).
“More studies are needed in high-risk individuals with high-risk kidney disease and/or cardiovascular disease but without type 2 diabetes as well as in individuals with type 1 diabetes,” Badve said.
For more information:
Sunil V. Badve, MBBS, MD, PhD, FRACP, can be reached at sbadve@georgeinstitute.org.au.
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