Evidence mapPaperPMID 40932012Full record

SynthesisDiabetes, obesity & metabolism2025

Sex differences in the efficacy of GLP-1 receptor agonists: A systematic review and meta-analysis of cardiovascular and renal outcome trials.

Hasan Fareed Siddiqui, Dua Ali, Maryam Sajid, Shaheer Qureshi, Hibah Siddiqui, Ali Hasan, David Ripley, Raheel Ahmed, Saad Ahmed Waqas

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Cardiorenal outcomes of weight loss interventions in people with CKD and type 2 diabetes.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Article
  3. Article
  4. Review
4 · The record

Corrections and comments

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

5 · Who and what money

Authors and funding

9 authors.

Hasan Fareed SiddiquiDepartment of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Dua AliDepartment of Medicine, Dow University of Health Sciences, Karachi, Pakistan.ORCID https://orcid.org/0009-0003-9925-2098
Maryam SajidDepartment of Medicine, Dow University of Health Sciences, Karachi, Pakistan.ORCID https://orcid.org/0009-0007-3544-3513
Shaheer QureshiDepartment of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Hibah SiddiquiDepartment of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Ali HasanDepartment of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
David RipleyDepartment of Medicine, Northumbria Hospitals NHS Foundation Trust, Tyneside, Tyne and Wear, UK.
Raheel AhmedDepartment of Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
Saad Ahmed WaqasDepartment of Medicine, Dow University of Health Sciences, Karachi, Pakistan.ORCID https://orcid.org/0009-0008-9051-6081

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sex-based differences in the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on cardiovascular, renal, and cerebrovascular outcomes remain unclear. This systematic review and meta-analysis evaluated sex-specific effects of GLP-1RAs in patients with type 2 diabetes mellitus and related comorbidities. Randomised controlled trials and secondary analyses comparing GLP-1RAs with placebo and reporting sex-stratified data were included. Outcomes assessed included composite kidney outcomes, 3-point major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke), individual components of MACE, and hospitalization for heart failure (HHF). Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Eleven trials comprising 85,273 patients (43, 339 receiving GLP-1RAs; 41, 934 placebo) were analysed. GLP-1RAs significantly reduced the risk of composite kidney outcomes by 20% in males (HR: 0.80; 95% CI: 0.69-0.92) and 31% in females (HR: 0.69; 95% CI: 0.54-0.87), with no significant sex interaction (p = 0.31). The risk of 3-point MACE was reduced by 14% in males (HR: 0.86; 95% CI: 0.79-0.93) and 18% in females (HR: 0.82; 95% CI: 0.75-0.90; p = 0.47). Stroke risk decreased by 21% in males and 25% in females. No significant sex-based differences were observed for cardiovascular death, myocardial infarction, or HHF. GLP-1RAs reduce the risk of major cardiovascular, kidney, and cerebrovascular outcomes in both sexes, with consistent benefits across men and women. While variations between sexes were observed in certain outcomes, these differences did not reach statistical significance for interaction. Future trials should improve female representation and explore sex-specific effects further.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsFemaleHumansMaleRandomized Controlled Trials as TopicSex FactorsTreatment OutcomeGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic Agentsgender differencesGLP‐1 receptor agonistshospitalization for heart failureMACEmyocardial infarctionstroke

Identifiers

PMID40932012
PMCPMC12587241

What Socratic holds

Textmetadata
LicenceCC BY
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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.