Study · Systematic review · n = 7,215 · 2022

4 results

Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.

Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S

Nature medicine24 Feb 2022Cited by 268 (Europe PMC)

PMID35210595PMCIDPMC8938269DOI10.1038/s41591-022-01707-4PepBankPUB-35210595

Summary

Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS. The pre-specified primary objective of this meta-analysis was the comparison of the time to first occurrence of confirmed four-component major adverse cardiovascular events (MACE-4; cardiovascular death, myocardial infarction, stroke and hospitalized unstable angina) between pooled tirzepatide groups and control groups. A stratified Cox proportional hazards model, with treatment as a fixed effect and trial-level cardiovascular risk as the stratification factor, was used for the estimation of hazard ratios (HRs) and confidence intervals (CIs) comparing tirzepatide to control. Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed. Overall, 142 participants, 109 from the trial with high cardiovascular risk and 33 from the six trials with lower cardiovascular risk, had at least one MACE-4 event. The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57-1.11) for MACE-4; 0.90 (95% CI, 0.50-1.61) for cardiovascular death; and 0.80 (95% CI, 0.51-1.25) for all-cause death. No evidence of effect modifications was observed for any subgroups, although the evidence was stronger for participants with high cardiovascular risk. Tirzepatide did not increase the risk of major cardiovascular events in participants with T2D versus controls.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

01HumanSystematic reviewSafety outcome
In adults with type 2 diabetes, tirzepatide did not significantly change the risk of four-component major adverse cardiovascular events compared with control (hazard ratio 0.80).
In plain wordsIn adults with type 2 diabetes, tirzepatide did not significantly change the risk of major heart events compared with control.
Peptide
Tirzepatide
Outcome
No significant changeMACE-4 versus control
Study
n = 7,215
Comparator
Control (pooled)
Analysis
Primary
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
Hazard ratio
0.8
MACE-4, tirzepatide vs control
Source sentences
Summary
The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57-1.11) for MACE-4; 0.90 (95% CI, 0.50-1.61) for cardiovascular death; and 0.80 (95% CI, 0.51-1.25) for all-cause death.
2 context sentences(design, population, supporting numbers)
Summary · context
This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS.
Summary · context
Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed.
Show in the study text Report a problemFND-3521059501
02HumanSystematic reviewSafety outcome
In adults with type 2 diabetes, tirzepatide did not significantly change the risk of cardiovascular death compared with control (hazard ratio 0.90).
In plain wordsIn adults with type 2 diabetes, tirzepatide did not significantly change the risk of death from heart disease compared with control.
Peptide
Tirzepatide
Outcome
No significant changeCardiovascular death versus control
Study
n = 7,215
Comparator
Control (pooled)
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
Hazard ratio
0.9
cardiovascular death, tirzepatide vs control
Source sentences
Summary
The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57-1.11) for MACE-4; 0.90 (95% CI, 0.50-1.61) for cardiovascular death; and 0.80 (95% CI, 0.51-1.25) for all-cause death.
2 context sentences(design, population, supporting numbers)
Summary · context
This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS.
Summary · context
Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed.
Show in the study text Report a problemFND-3521059502
03HumanSystematic reviewSafety outcome
In adults with type 2 diabetes, tirzepatide did not significantly change the risk of all-cause death compared with control (hazard ratio 0.80).
In plain wordsIn adults with type 2 diabetes, tirzepatide did not significantly change the risk of death from any cause compared with control.
Peptide
Tirzepatide
Outcome
No significant changeAll-cause death versus control
Study
n = 7,215
Comparator
Control (pooled)
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Measurements
Hazard ratio
0.8
all-cause death, tirzepatide vs control
Source sentences
Summary
The HRs comparing tirzepatide versus controls were 0.80 (95% CI, 0.57-1.11) for MACE-4; 0.90 (95% CI, 0.50-1.61) for cardiovascular death; and 0.80 (95% CI, 0.51-1.25) for all-cause death.
2 context sentences(design, population, supporting numbers)
Summary · context
This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS.
Summary · context
Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed.
Show in the study text Report a problemFND-3521059503
04HumanSystematic reviewSafety outcome
In adults with type 2 diabetes, no evidence of effect modification was seen for any subgroup in the cardiovascular event analysis of tirzepatide.
In plain wordsIn adults with type 2 diabetes, the heart-event results for tirzepatide did not differ between subgroups.
Peptide
Tirzepatide
Outcome
No significant changeEffect modification by subgroup
Study
n = 7,215
Comparator
Control (pooled)
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
No evidence of effect modifications was observed for any subgroups
2 context sentences(design, population, supporting numbers)
Summary · context
This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS.
Summary · context
Data from 4,887 participants treated with tirzepatide and 2,328 control participants were analyzed.
Show in the study text Report a problemFND-3521059504

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials7

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

7 trials · 7 completed · 7 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT04039503

A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

Eli Lilly and Companyn = 47530 Aug 2019 to 13 Jan 2021

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 12 Jan 2022

CompletedPhase 3Results postedNCT03987919

A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 1,87930 Jul 2019 to 15 Feb 2021

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 14 Feb 2022

CompletedPhase 3Results postedNCT03954834

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone

Eli Lilly and Companyn = 4783 Jun 2019 to 28 Oct 2020

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 20 Oct 2021

CompletedPhase 3Results postedNCT03861052

A Study of Tirzepatide (LY3298176) Compared to Dulaglutide in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 6367 May 2019 to 31 Mar 2021

Type 2 Diabetes

Trial page ClinicalTrials.govUpdated 14 Apr 2022

CompletedPhase 3Results postedNCT03882970

A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

Eli Lilly and Companyn = 1,4441 Apr 2019 to 4 Jan 2021

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 19 Jan 2022

CompletedPhase 3Results postedNCT03730662

A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk

Eli Lilly and Companyn = 2,00220 Nov 2018 to 22 Apr 2021

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 14 Feb 2022

CompletedPhase 2Results postedNCT03131687

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Mellitus

Eli Lilly and Companyn = 31824 May 2017 to 1 Aug 2018

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 20 Aug 2019

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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