Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials
- Design
- Meta-analysis · 85373 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationDiabetes trials plus SELECT; no heterogeneity between SELECT and the diabetes trials, which modestly extends the finding to obesity without diabetes.
- Could weight loss explain it?
- Possibly[Auto] Not addressed in abstract.
- Study tier
- Study tier 1Meta-analysis of large randomized trials with hard kidney outcomes.
- Assessment
- Version 2 · curated · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
Across 11 randomized trials (85,373 people, mostly with type 2 diabetes), GLP-1 receptor agonists reduced kidney failure by 16% and a composite kidney outcome by 18%, with consistent results when SELECT was added. No increase in serious adverse events or pancreatitis.
01Findings
What the study reported
- Drugs
- Class unspecified, Semaglutide, Liraglutide, Dulaglutide, Exenatide, Efpeglenatide
- Comparator
- placebo
- Primary outcome
- Composite kidney outcome (kidney failure, sustained >=50% eGFR loss, kidney death) and MACE across 11 RCTs
- Effect
- Kidney composite HR 0.82; kidney failure HR 0.84; MACE HR 0.87; all-cause death HR 0.88 (T2D); similar including SELECT
- 95% confidence interval
- 0.73 to 0.93 (kidney composite)
- Follow-up
- 12 months of follow-up
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Bmi mean
- 27
- Bmi min
- 27
- Diabetes status
- type 2 diabetes in 10 trials; SELECT (no diabetes, obesity) added post hoc
- Cvd status
- cardiovascular disease present in population (see abstract)
- Sample size
- 500
Study quality details
- Study design
- Meta-analysis
- Sample size
- 500
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- Follow up duration
- 12 months of follow-up
- Outcome type
- mixed
- Replication
- 11 trials; low heterogeneity for kidney failure
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- UNKNOWN
- Statistical precision
- CI reported: 95% CI 0·73-0·93
- Risk of bias
- trial-level; SELECT added post hoc
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Not stated in abstract
- Industry funded
- Unclear
- Manufacturer
- Novo Nordisk, Eli Lilly, Lilly, AstraZeneca, Sanofi, Boehringer Ingelheim, Amgen, Pfizer, Roche, Hanmi
- Sponsor role
- not reported in abstract
- Author conflicts
- Authors report consulting/speaking fees from Bayer, AstraZeneca, Novo Nordisk and others.
- Independent replication
- yes (consistent with PMID 34425083)
Funding is shown on every study and never used to score it.
03Claims
Claims this study bears on
- GLP-1 receptor agonists protect kidney function in people without diabetes.Supports
Meta-analysis of 11 RCTs: composite kidney outcome HR 0.82; SELECT consistent.
04Source
The source, as retrieved
Abstract
[BACKGROUND] GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials. [METHODS] For this meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials that included at least 500 participants with type 2 diabetes, compared a GLP-1 receptor agonist with placebo with at least 12 months of follow-up, and reported a primary clinical kidney or cardiovascular outcome, from database inception to March 26, 2024. Post hoc, we included the SELECT trial (NCT03574597), which enrolled participants with cardiovascular disease and a BMI of 27 kg/m2 or more without diabetes. Study-level summary data were extracted independently by two authors for inclusion in this random-effects analysis. The main kidney outcome was a composite outcome, consisting of kidney failure (kidney replacement therapy or a persistent estimated glomerular filtration rate [eGFR] <15 mL/min per 1·73 m2), a sustained reduction in eGFR by at least 50% or the nearest equivalent, or death from kidney failure. The main cardiovascular outcome was MACE, consisting of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. This study is registered with PROSPERO, CRD42024528864. [FINDINGS] Of the 5140 records identified through the literature search, 11 trials, involving 85 373 participants (29 386 female, 55 987 male), were included in the meta-analysis. In participants with type 2 diabetes (67 769), GLP-1 receptor agonists reduced the composite kidney outcome by 18% compared with placebo (hazard ratio [HR] 0·82, 95% CI 0·73-0·93; I2 =26·41%), kidney failure by 16% (HR 0·84, 0·72-0·99; I2 =0%), MACE by 13% (HR 0·87, 0·81-0·93; I2 =49·75%), and all-cause death by 12% (HR 0·88, 0·83-0·93; I2 =0%). The effect on the composite kidney outcome (HR 0·81, 95% CI 0·72-0·92; I2 =23·11%), kidney failure (HR 0·84, 0·72-0·98; I2 =0%), MACE (HR 0·86, 0·80-0·92; I2 =48·9%), and all-cause death (HR 0·87, 0·82-0·91; I2 =0%) was similar when the SELECT trial was included, with no evidence of heterogeneity between this trial and those including participants with type 2 diabetes (pheterogeneity >0·05). There was no difference in the risk of serious adverse events, including acute pancreatitis and severe hypoglycaemia, between the GLP-1 receptor agonist and placebo groups (risk ratio [RR] 0·95, 95% CI 0·90-1·01; I2 =88·5%). However, treatment discontinuation due to adverse events occurred more frequently in the GLP-1 receptor agonist groups (RR 1·51, 95% CI 1·18-1·94; I2 =96·3%). [INTERPRETATION] We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events. [FUNDING] None.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 39608381 first ingestion |