Cardiovascular Efficacy of GLP-1 Receptor Agonists by Kidney Function: An Updated Meta-Analysis of Randomized Trials Including the SOUL Trial
Abstract
Aims: To evaluate the cardiovascular efficacy and absolute benefit of glucagon-like peptide-1 receptor agonists (GLP-1RAs) by baseline estimated glomerular filtration rate (eGFR).
Materials and methods: PubMed and EMBASE were searched to 29 April 2026 for randomized placebo-controlled trials of GLP-1RAs in adults with type 2 diabetes or overweight/obesity that reported eGFR-stratified major adverse cardiovascular events (MACE). Hazard ratios (HRs) were extracted for eGFR 2. Random-effects meta-analyses estimated pooled HRs within each eGFR stratum and the pooled ratio of HRs (RHR) comparing eGFR 2. Exploratory absolute risk reduction (ARR) and number needed to treat (NNT) were derived from placebo-group MACE risk and the corresponding pooled HR.
Results: Nine publications from eight trials were included, comprising 70 822 participants; 70 534 had eGFR-stratified MACE data. GLP-1RAs similarly reduced MACE risk among participants with eGFR ≥ 60 and 2, with pooled HRs of 0.83 (95% CI 0.77-0.90; p 2 = 35.6%) and 0.83 (95% CI 0.74-0.93; p 2 = 40.9%), respectively. The pooled RHR showed no evidence of effect modification (1.02, 95% CI 0.85-1.21; p = 0.84). ARR was larger with eGFR 2 (2.6% vs. 1.6%), corresponding to NNTs of 39 (95% CI 26-91) versus 62 (95% CI 46-101).
Conclusions: GLP-1RAs reduced MACE risk similarly across eGFR strata, while lower eGFR was associated with a larger estimated absolute cardiovascular benefit. These findings support GLP-1RA therapy in individuals…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 70 participants or records.
Read the paper
Related studies
- Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis
- Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials
- Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials
- Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta‐analysis, and network meta‐analysis of randomized trials with 94,283 participants
- Screen time increases overweight and obesity risk among adolescents: a systematic review and dose-response meta-analysis
- Exposure to WHO AWaRe antibiotics and isolation of multi-drug resistant bacteria: a systematic review and meta-analysis
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.