SynthesisDiabetes, obesity & metabolism2026

Efficacy and Safety of GLP-1 Receptor Agonists on Combined Cardiovascular and Renal Outcomes in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

Rashpinder Kaur, Avtar Singh

Abstract readSystematic ReviewNetwork Meta-Analysis
In one paragraph

Synthesis in Diabetes, obesity & metabolism, 2026. The graph read 2 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. Cited by 1 paper, 1 of them a synthesis that pooled it.

2numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Read, but not usablea number the graph found but could not read as for or against

Kidney outcomescomparator not stated · ascvd, t2dfeeds one cell of the map
HR 0.790.73 to 0.86
GLP-1 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79-0.89; high certainty) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73-0.86; high certainty).
Cardiovascular eventscomparator not stated · ascvd, t2dfeeds one cell of the map
HR 0.840.79 to 0.89
GLP-1 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79-0.89; high certainty) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73-0.86; high certainty).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×kidney outcomes

No readable resultOpen on the map →What to test next →

7 readable studies in this cell: 3 favour the treatment, 4 find no difference, 0 favour the comparator.

Belief with this paper
0.50contested · 2 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT011790489,341 enrolled · 2010
HR 0.780.67 to 0.92
NCT038191533,533 enrolled · 2019
HR 0.760.66 to 0.88
NCT017204463,297 enrolled · 2013
Treatment ratio 0.780.68 to 0.89
NCT01620489279 enrolled · 2012
Estimated treatment ratio 0.980.94 to 1.02
NCT04865770106 enrolled · 2021
Treatment ratio 0.980.96 to 1.01

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

GLP-1 receptor agonists×cardiovascular events

No readable resultOpen on the map →What to test next →

13 readable studies in this cell: 7 favour the treatment, 2 find no difference, 4 favour the comparator.

Belief with this paper
0.50contested · 7 families support, 3 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0357459717,604 enrolled · 2018
HR 0.800.72 to 0.89
NCT013949529,901 enrolled · 2011
HR 0.880.79 to 0.99
NCT039143269,651 enrolled · 2019
HR 0.860.77 to 0.96
NCT011790489,341 enrolled · 2010
HR 0.870.78 to 0.97
NCT038191533,533 enrolled · 2019
HR 0.760.66 to 0.88
NCT017204463,297 enrolled · 2013
HR 0.740.58 to 0.95
NCT026927163,183 enrolled · 2017
HR 0.790.57 to 1.11
OR 1.951.28 to 3.00
NCT05564039282 enrolled · 2022
OR 20.48.40 to 49.8

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

2 authors.

Rashpinder KaurGeneral Medicine and Care of the Elderly, Aneurin Bevan University Health Board, Newport, UK.
Avtar SinghGeneral Medicine and Care of the Elderly, Aneurin Bevan University Health Board, Newport, UK.ORCID https://orcid.org/0009-0009-4705-0818

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

aimsChronic kidney disease (CKD) confers substantial cardiovascular and renal morbidity. GLP-1 receptor agonists (GLP-1 RAs) have demonstrated cardiorenal protection across major randomised trials, culminating in the landmark FLOW trial. No prior systematic review has simultaneously synthesised cardiorenal outcomes in a CKD-restricted population, executed a network meta-analysis for agent-level comparisons, or assessed whether SGLT2 inhibitor background therapy modifies treatment effects. MATERIALS AND

methodsMEDLINE, Embase, Cochrane CENTRAL, and Web of Science were searched through March 2025. Eligible RCTs enrolled adults with CKD (eGFR < 60 mL/min/1.73 m

resultsThirteen RCTs (97 428 participants; 31 846 with confirmed CKD) were included. GLP-1 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79-0.89; high certainty) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73-0.86; high certainty). Kidney failure risk was reduced by 28% (HR 0.72); UACR decreased by 26%. Benefits were consistent irrespective of SGLT2 inhibitor background use (interaction p = 0.41). Semaglutide ranked highest in the NMA (SUCRA 78.4%). No excess acute kidney injury risk was observed.

conclusionsGLP-1 RAs provide clinically meaningful cardiorenal protection in CKD, additive to SGLT2 inhibitor benefits. In exploratory network meta-analysis, semaglutide subcutaneous achieved the highest SUCRA ranking for kidney composite outcomes; the direct semaglutide evidence is rated high certainty by GRADE.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsRenal Insufficiency, ChronicHumansKidneyRandomized Controlled Trials as TopicSemaglutideSodium-Glucose Transporter 2 InhibitorsTreatment OutcomeGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsSemaglutideSodium-Glucose Transporter 2 Inhibitorscardiorenal protectioncardiovascular outcomeschronic kidney diseasecomposite kidney endpointGLP‐1 receptor agonistsMACEsemaglutideSGLT2 inhibitors

Identifiers

PMID42337824
PMCPMC13448877

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.