Cardiovascular Efficacy of GLP-1 Receptor Agonists by Kidney Function: An Updated Meta-Analysis of Randomized Trials Including the SOUL Trial.
GLP-1 receptor agonists reduce major adverse cardiovascular events similarly in patients with different kidney functions, with a greater absolute benefit seen in those with lower kidney function.
Where it sits
this study against the rest of the albiglutide corpusSummary and findings
This meta-analysis evaluated the cardiovascular efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) based on kidney function in adults with type 2 diabetes or overweight/obesity. It included data from nine publications involving 70,822 participants, focusing on major adverse cardiovascular events (MACE) stratified by estimated glomerular filtration rate (eGFR). The findings indicated similar reductions in MACE risk across different eGFR levels.
Abstract
<h4>Aims</h4>To evaluate the cardiovascular efficacy and absolute benefit of glucagon-like peptide-1 receptor agonists (GLP-1RAs) by baseline estimated glomerular filtration rate (eGFR).<h4>Materials and methods</h4>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 < 60 and ≥ 60 mL/min/1.73 m<sup>2</sup>. Random-effects meta-analyses estimated pooled HRs within each eGFR stratum and the pooled ratio of HRs (RHR) comparing eGFR < 60 versus ≥ 60 mL/min/1.73 m<sup>2</sup>. Exploratory absolute risk reduction (ARR) and number needed to treat (NNT) were derived from placebo-group MACE risk and the corresponding pooled HR.<h4>Results</h4>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 < 60 mL/min/1.73 m<sup>2</sup>, with pooled HRs of 0.83 (95% CI 0.77-0.90; p < 0.001; I <sup>2</sup> = 35.6%) and 0.83 (95% CI 0.74-0.93; p < 0.001; I <sup>2</sup> = 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 < 60 than ≥ 60 mL/min/1.73 m<sup>2</sup> (2.6% vs. 1.6%), corresponding to NNTs of 39 (95% CI 26-91) versus 62 (95% CI 46-101).<h4>Conclusions</h4>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 with reduced kidney function.
Background
This paper addresses the cardiovascular efficacy of GLP-1 receptor agonists (GLP-1RAs) in relation to kidney function, specifically estimated glomerular filtration rate (eGFR). Prior studies have indicated potential cardiovascular benefits of GLP-1RAs, but the impact of kidney function on these outcomes was less clear. Understanding how eGFR affects the efficacy of GLP-1RAs is important for optimizing treatment strategies in populations with varying kidney function.
Methods
The study conducted a systematic review and meta-analysis of randomized placebo-controlled trials involving adults with type 2 diabetes or overweight/obesity. A total of nine publications from eight trials were included, with 70,822 participants, of which 70,534 had eGFR-stratified MACE data. The analysis focused on hazard ratios (HRs) for MACE based on eGFR levels, with additional calculations for absolute risk reduction (ARR) and number needed to treat (NNT).
Results
The primary endpoint showed that GLP-1RAs reduced MACE risk similarly for participants with eGFR ≥ 60 and < 60 mL/min/1.73 m², with pooled HRs of 0.83 for both groups (95% CI 0.77-0.90; p < 0.001 for eGFR ≥ 60 and 95% CI 0.74-0.93; p < 0.001 for eGFR < 60). The pooled ratio of hazard ratios (RHR) indicated no evidence of effect modification (1.02, 95% CI 0.85-1.21; p = 0.84). ARR was larger for eGFR < 60 at 2.6% compared to 1.6% for eGFR ≥ 60, leading to NNTs of 39 and 62, respectively.
Interpretation
The findings suggest that GLP-1RAs provide similar cardiovascular benefits across different levels of kidney function, with a greater absolute benefit observed in those with lower eGFR. While the statistical significance is clear, the clinical significance may vary based on individual patient factors. Limitations include the potential for confounding variables not accounted for in the meta-analysis, and the reliance on previously published data, which may vary in quality.
Key findings
- Pooled HR for MACE with eGFR ≥ 60 mL/min/1.73 m² was 0.83 (95% CI 0.77-0.90; p < 0.001; I² = 35.6%)
- Pooled HR for MACE with eGFR < 60 mL/min/1.73 m² was 0.83 (95% CI 0.74-0.93; p < 0.001; I² = 40.9%)
- Pooled RHR comparing eGFR < 60 versus ≥ 60 mL/min/1.73 m² was 1.02 (95% CI 0.85-1.21; p = 0.84)
- Absolute risk reduction (ARR) was 2.6% for eGFR < 60 and 1.6% for eGFR ≥ 60 mL/min/1.73 m²
- Number needed to treat (NNT) was 39 (95% CI 26-91) for eGFR < 60 and 62 (95% CI 46-101) for eGFR ≥ 60
Limitations
- Meta-analysis may include variability in trial quality and design
- Findings limited to reported data and may not account for all confounding factors
- Not all trials may have been included in the analysis