GLP-1 Receptor Agonists and Dual GIP/GLP-1 and Reduction in Major Cardiovascular Events: A Systematic Review and Network Meta-Analysis
- Design
- Systematic review · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: the planned review covers trials in adults with type 2 diabetes, which the target group does not have.
- Could weight loss explain it?
- PossiblyNo results and no weight, HbA1c or mediation analysis are described; any future cardiovascular effect would be presumed confounded with weight and glycaemic change unless separated.
- Study tier
- Not ratedNOT_RATED: protocol for a systematic review and network meta-analysis with no pooled estimate and no outcome data; it is also a preprint, not peer reviewed.
- Assessment
- Version 2 · Two reviewers differed; settled by a recorded ruling · Oct 19, 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. This item has not been peer reviewed.
This is a protocol, not a result: a planned network meta-analysis of randomised trials lasting at least 52 weeks in adults with type 2 diabetes, comparing GLP-1 drugs and tirzepatide for major cardiovascular events (cardiovascular death, heart attack and stroke). It reports no findings yet and has been posted as a preprint, not peer reviewed.
01Findings
What the study reported
- Drugs
- Glp-1 receptor agonists, Tirzepatide
- Comparator
- placebo, standard care, another eligible incretin therapy, or an SGLT2 inhibitor or basal insulin as connector nodes
- Dose
- various
- Primary outcome
- time to first three-point MACE (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke)
- Effect
- not reported in abstract
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- not reported in abstract
- Limitations
- Protocol for a planned network meta-analysis with no results; posted as a preprint, not peer reviewed.
Who was studied
- Obesity status
- not reported in abstract
- Diabetes status
- type 2 diabetes required
- Cvd status
- not reported in abstract
- Ckd status
- not reported in abstract
- Baseline condition
- type 2 diabetes
- Inclusion exclusion
- parallel-group randomized controlled trials with at least 52 weeks of follow-up in adults with type 2 diabetes
Study quality details
- Study design
- Systematic review
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- n/a
- Comparator
- placebo, standard care, another eligible incretin therapy, or an SGLT2 inhibitor or basal insulin as connector nodes
- Follow up duration
- not stated
- Outcome type
- hard
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- no CI reported; protocol with no results
- Risk of bias
- not assessed
- Funding conflicts
- unclear
- Peer review status
- no
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- not stated in source
- Sponsor role
- not reported in abstract
- Author conflicts
- not reported in abstract
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
<h4>Background: </h4> Type 2 diabetes is a cause of cardiovascular morbidity and mortality. Although gluca-gon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists improve cardiovascular outcomes, their comparative effects across the class re-main uncertain because direct head-to-head evidence is limited. <h4>Objective:</h4> To compare these agents for major adverse cardiovascular events (MACE) and establish a treatment hierarchy. <h4>Methods:</h4> This systematic review and network meta-analysis will include parallel-group randomized controlled trials with at least 52 weeks of follow-up involving adults with type 2 diabetes. Eligible trials will compare a GLP-1 receptor agonist or tirzepatide with placebo, standard care, another eligible in-cretin therapy, or, as connector nodes, an SGLT2 inhibitor or basal insulin. The primary outcome is time to first three-point MACE, comprising cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. MEDLINE, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP, will be searched without date or language restrictions. Study selection and data extraction will involve human verification, and risk of bias will be assessed using RoB 2. A frequentist ran-dom-effects network meta-analysis will estimate hazard ratios, using placebo as the reference, and rank treatments with P-scores. Transitivity, heterogeneity, and inconsistency will be evaluated through prespecified effect modifiers, node-splitting, and design-by-treatment interaction methods. Confidence in network estimates will be assessed with CINeMA, alongside GRADE for pairwise comparisons. Ethics and dissemination: Ethical approval is unnecessary because only published data will be used. Results, datasets, search strategies, and analytic code will be disseminated through publications, presentations, bilingual summaries, and open repositories.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| europepmc | Oct 11, 2026 | PPR:PPR1336358 first ingestion |
| europepmc | Oct 18, 2026 | PPR:PPR1336358 duplicate matched on doi |