GLP-1 Evidence

Not medical advice. A record of published research and our assessments of it. The limits

Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes

Design
Randomized trial · 3533 participants · Hard outcome
Match to healthy normal-weight adults aged 55–75
Different populationEvery participant had type 2 diabetes and albuminuric CKD. No inference to people with normal kidney function and no diabetes.
Could weight loss explain it?
PossiblyBenefit could partly reflect glycaemic, blood-pressure and weight effects; the abstract does not report mediation analysis. Dose (1.0 mg) is below obesity doses.
Study tier
Study tier 1Large placebo-controlled outcome trial with hard kidney endpoints; early termination is a recognised source of effect inflation.
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.

In 3,533 people with type 2 diabetes and kidney disease, semaglutide 1.0 mg weekly reduced major kidney events by about a quarter and all-cause death by a fifth over 3.4 years. The trial was stopped early for benefit. It applies to people with diabetic kidney disease, not to healthy kidneys.

01Findings

What the study reported

Drugs
Semaglutide
Dose
1.0 mg once weekly
Route
subcutaneous
Treatment duration
median 3.4 years
Comparator
placebo
Primary outcome
Major kidney disease events (kidney failure, >=50% eGFR reduction, kidney or CV death)
Effect
HR 0.76 (331 vs 410 events); all-cause death HR 0.80
95% confidence interval
0.66 to 0.88
P value
0.0003
Follow-up
median 3.4 years (stopped early for efficacy)
Adverse events
Serious adverse events lower with semaglutide (49.6% vs 53.8%).
Limitations
Diabetic CKD population; early stopping.

Who was studied

Obesity status
not an entry criterion (mean BMI ~32 in full text)
Diabetes status
type 2 diabetes required (all)
Cvd status
mixed
Ckd status
CKD with albuminuria required (eGFR 25-75)
Baseline condition
chronic kidney disease
Sample size
3533

Study quality details

Study design
Randomized controlled trial
Sample size
3533
Randomization
yes
Blinding
double-blind
Comparator
placebo
Follow up duration
3.4 years
Outcome type
mixed
Replication
consistent with kidney signals in SUSTAIN-6/LEADER and meta-analysis (PMID 39608381)
Consistency with other evidence
not assessed (auto)
Population applicability
INDIRECT
Statistical precision
CI reported: 95% confidence interval [CI], 0
Risk of bias
early stopping at interim analysis may overestimate effect size
Funding conflicts
yes
Peer review status
yes
02Funding

Funding and conflicts

Funding
Novo Nordisk (NIH support listed in PubMed grant fields)
Industry funded
Yes
Manufacturer
Novo Nordisk
Sponsor role
Sponsor-designed and sponsor-analysed trial with academic steering committee.
Author conflicts
Authors report Novo Nordisk relationships; sponsor employees co-authored (see disclosures).
Independent replication
no; class-level consistency
Notes
Pivotal industry trial.

Funding is shown on every study and never used to score it.

03Claims

Claims this study bears on

04Source

The source, as retrieved

Abstract

[BACKGROUND] Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown. [METHODS] We randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically. [RESULTS] Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m2 in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P = 0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%). [CONCLUSIONS] Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW ClinicalTrials.gov number, NCT03819153.).

Where this record came from

SourceRetrievedIdentifier
pubmedSep 13, 202638785209
first ingestion