SynthesisCardiovascular diabetology2026

Comparative efficacy of tirzepatide and glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in patients with type 2 diabetes: a systematic review and network meta-analysis.

Arveen Shokravi, Jayant Seth, G B John Mancini

Abstract readSystematic ReviewNetwork Meta-Analysis
In one paragraph

Synthesis in Cardiovascular diabetology, 2026. The graph read 7 numbers from its abstract, feeding 3 cells of the map: it supports the treatment in 3. Cited by 3 papers, 1 of them a synthesis that pooled it.

7numbers the graph read from it
3cells of the map it votes in
3citing 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.

← favours the treatmentfavours the comparator →
1 · no effect
Cardiovascular eventsfavours the treatment · against placebo · ascvd, t2dfeeds one cell of the map
HR 0.810.70 to 0.94
In the agent-level analysis, tirzepatide reduced MACE compared to placebo (HR 0.81, 95% CI 0.70-0.94) and lixisenatide (HR 0.79, 95% CI 0.65-0.97).
Cardiovascular eventsfavours the treatment · against placebo · ascvd, t2dfeeds one cell of the map
HR 0.790.69 to 0.91
In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo.
Cardiovascular eventsfavours the treatment · against placebo · ascvd, t2dfeeds one cell of the map
HR 0.770.66 to 0.90
In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo.
All-cause mortalityfavours the treatment · against placebo · ascvd, t2dfeeds one cell of the map
HR 0.740.65 to 0.83
In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo.
All-cause mortalityfavours the treatment · against placebo · ascvd, t2dfeeds one cell of the map
HR 0.770.61 to 0.97
In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo.
Cardiovascular eventsfavours the treatment · against placebo · ascvd, t2dfeeds one cell of the map
HR 0.790.65 to 0.97
In the agent-level analysis, tirzepatide reduced MACE compared to placebo (HR 0.81, 95% CI 0.70-0.94) and lixisenatide (HR 0.79, 95% CI 0.65-0.97).
All-cause mortalityfavours the treatment · against placebo · ascvd, t2dfeeds one cell of the map
HR 0.790.64 to 0.97
In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo.

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.

GIP/GLP-1 & amylin agonists×all-cause mortality

SupportsOpen on the map →What to test next →

2 readable studies in this cell: 1 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.35one trial · 1 family supports, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT04847557731 enrolled · 2021
HR 1.250.63 to 2.45

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

GIP/GLP-1 & amylin agonists×cardiovascular events

SupportsOpen on the map →What to test next →

2 readable studies in this cell: 2 favour the treatment, 0 find no difference, 0 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT04847557731 enrolled · 2021
HR 0.620.41 to 0.95
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.

GLP-1 receptor agonists×cardiovascular events

SupportsOpen 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

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

  1. Pooled it
  2. Review
  3. Review
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

3 authors.

Arveen ShokraviDepartment of Medicine, Faculty of Medicine, The University of British Columbia, 6200 University Blvd, Vancouver, BC, V6T1Z3, Canada. shokravi@student.ubc.ca.
Jayant SethDepartment of Medicine, Faculty of Medicine, The University of British Columbia, 6200 University Blvd, Vancouver, BC, V6T1Z3, Canada.
G B John ManciniDepartment of Medicine, Faculty of Medicine, The University of British Columbia, 6200 University Blvd, Vancouver, BC, V6T1Z3, Canada.

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.

backgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used therapies for cardiovascular risk reduction in type 2 diabetes (T2D). With the emergence of the SURPASS-CVOT trial, tirzepatide (a dual GIP/GLP-1 receptor agonist) has entered the therapeutic landscape; however, its comparative effect on cardiovascular outcomes compared to placebo and individual GLP-1RAs remains undefined.

methodsWe conducted a systematic review and frequentist network meta-analysis (NMA) of RCTs enrolling adults with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (ASCVD) or high cardiovascular (CV) risk. Eligible RCTs evaluated tirzepatide or GLP-1RAs and reported major adverse cardiovascular events (MACE), CV mortality, all-cause mortality, non-fatal myocardial infarction (MI) or non-fatal stroke. A class-level NMA was conducted to estimate the incremental benefit of tirzepatide and GLP-1RAs over placebo, and an agent-level NMA was conducted to explore differences between tirzepatide and individual GLP-1RA agents. Subgroup analyses, including established cardiovascular disease populations, and leave-one-out sensitivity analyses were performed.

resultsEleven trials met inclusion criteria (10 GLP-1RA trials and 1 tirzepatide trial [SURPASS-CVOT]). In the class-level analysis, tirzepatide significantly reduced MACE (HR 0.79, 95% CI 0.69-0.91), CV mortality (HR 0.77, 95% CI 0.66-0.90), all-cause mortality (HR 0.74, 95% CI 0.65-0.83), non-fatal MI (HR 0.77, 95% CI 0.61-0.97), and non-fatal stroke (HR 0.79, 95% CI 0.64-0.97) compared to placebo. Formal statistical comparisons between tirzepatide and the GLP-1RA class could not be performed within the constraints of the NMA; however, point estimates across outcomes numerically favored tirzepatide compared with placebo. In the agent-level analysis, tirzepatide reduced MACE compared to placebo (HR 0.81, 95% CI 0.70-0.94) and lixisenatide (HR 0.79, 95% CI 0.65-0.97). Subgroup and sensitivity analyses did not substantially change point estimates.

conclusionAmong adults with T2D and established ASCVD or high CV risk, class-level analysis demonstrated that tirzepatide significantly reduced the risk of cardiovascular events compared to placebo; at the agent-level, tirzepatide demonstrated comparable efficacy to individual GLP-1RAs. These findings suggest that tirzepatide provides cardiovascular benefit at least comparable to established GLP-1RAs, supporting its emerging role in cardiovascular risk reduction in T2D.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsIncretinsTirzepatideBiomarkersGlucagon-Like Peptide-1 ReceptorHeart Disease Risk FactorsHumansRandomized Controlled Trials as TopicRisk AssessmentTreatment OutcomeBiomarkersGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsIncretinsTirzepatidecardiovascular outcomesglucagon-like peptide-1 receptor agonistsmeta-analysistirzepatidetype 2 diabetes

Identifiers

PMID41761267
PMCPMC13049956

What Socratic holds

Texttitle and abstract
LicenceCC BY
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.