Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials
Authors' conclusion
We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events.
Study context
- Population
- RCTs with ≥500 participants with T2D, GLP-1 RA vs placebo, ≥12 months follow-up; post hoc SELECT trial (CVD, BMI ≥27 kg/m², no diabetes)
- Participants
- 85,373 participants11 trials
- Comparison
- GLP-1 RA vs placebo
- Outcome
- Main kidney outcome: composite of kidney failure (kidney replacement therapy or persistent eGFR <15 mL/min per 1.73 m²), sustained eGFR reduction ≥50% or nearest equivalent, or death from kidney failure; main CV outcome: MACE (CV death, non-fatal MI, non-fatal stroke)
Methodological detailsrandom-effects, SELECT trial included post hoc
- Random-effects
- SELECT trial included post hoc
Pooled result
As reported in the abstract
GLP-1 RA vs PlaceboHazard ratio (95% CI)
Composite kidney outcome; reduced by 18%; I2 =26.41%
0.82(0.73–0.93)
MACE; reduced by 13%; I2 =49.75%
0.87(0.81–0.93)
Further pooled results
| Outcome | HR | |
|---|---|---|
| Kidney failure, T2DGLP-1 RAvs PlaceboReduced by 16%; I2 =0% | 0.84 (CI 0.72–0.99) | |
| All-cause death, T2DGLP-1 RAvs PlaceboReduced by 12%; I2 =0% | 0.88 (CI 0.83–0.93) | |
| Including SELECT trial: composite kidney outcome, kidney failure, MACE, all-cause deathGLP-1 RAvs PlaceboComposite kidney outcome; I2 =23.11% | 0.81 (95% CI 0.72–0.92) | |
| Including SELECT trial: composite kidney outcome, kidney failure, MACE, all-cause deathGLP-1 RAvs PlaceboKidney failure; I2 =0% | 0.84 (95% CI 0.72–0.98) | |
| Including SELECT trial: composite kidney outcome, kidney failure, MACE, all-cause deathGLP-1 RAvs PlaceboMACE; I2 =48.9% | 0.86 (95% CI 0.80–0.92) | |
| Including SELECT trial: composite kidney outcome, kidney failure, MACE, all-cause deathGLP-1 RAvs PlaceboAll-cause death; I2 =0% | 0.87 (95% CI 0.82–0.91) | |
| 0.512Hazard ratio (log scale) |
- Including SELECT trial: composite kidney outcome, kidney failure, major adverse cardiovascular events (MACE), all-cause death — No evidence of heterogeneity between SELECT and T2D trials
- pheterogeneity >0.05
Safety
| Outcome | RR (95% CI) | |
|---|---|---|
| Serious adverse events, incl. acute pancreatitis and severe hypoglycaemiaGLP-1 RAvs PlaceboI2 =88.5% | 0.95 (0.90–1.01) | |
| Treatment discontinuation due to adverse eventsGLP-1 RAvs PlaceboMore frequent with GLP-1 RA; I2 =96.3% | 1.51 (1.18–1.94) | |
| 0.512Relative risk (log scale) |
Original publication
Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. Published 25 November 2024. doi:10.
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