Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials
A meta-analysis of 10 randomized trials in over 71,000 people with type 2 diabetes found that long-acting GLP-1 receptor agonists cut heart attacks and strokes, heart-failure hospitalizations, kidney failure events, and death, with the same benefit whether the drug was injected or taken by mouth.
Study design
The authors systematically reviewed PubMed through February 2025 for randomized, placebo-controlled cardiovascular and kidney outcome trials of long-acting GLP-1 receptor agonists enrolling at least 500 participants with type 2 diabetes. Ten trials totalling 71,351 participants were pooled in a random-effects meta-analysis, incorporating new data from the SOUL trial of oral semaglutide and the FLOW kidney-outcomes trial.
Key findings
Long-acting GLP-1 receptor agonists reduced major adverse cardiovascular events by 14% (HR 0.86, 95% CI 0.81-0.90), hospitalization for heart failure by 14% (HR 0.86), a composite kidney outcome by 17% (HR 0.83), and all-cause mortality by 12% (HR 0.88). A consistent 14% reduction was seen across all individual MACE components, and there was no significant heterogeneity by administration route (subcutaneous versus oral).
Safety
There were no increased risks of severe hypoglycaemia, retinopathy, or pancreatic events. The authors note that trial-level pooling precludes detailed subgroup analyses and may introduce ecological bias.
Clinical implications
For clinicians managing type 2 diabetes with cardiovascular or kidney risk, the analysis supports GLP-1 receptor agonists as a class with reproducible cardiorenal and survival benefit, and reassures that oral semaglutide delivers protection comparable to injectable agents.
Category
Research
Source
Diabetes Care
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