Preferred Glucagon-like Peptide-1 Receptor Agonists in Adults With Type 2 Diabetes and Established Cardiovascular Disease or High Cardiovascular Risk: A Network Meta-analysis of Randomized Trials.

Abomohsen M, Rifai M, Gadelmawla AF, Alghzawi HM, Elgendy MS, Bakr HM, Friedman A, Idries IY

Canadian journal of diabetes10 Apr 2026

PMID41967797DOI10.1016/j.jcjd.2026.04.001PepBankPUB-41967797

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study13

13 results from studies that gave the peptide. 13 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, subcutaneous semaglutide reduced MACE versus placebo (RR 0.74).
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, semaglutide injections lowered major heart events compared with placebo.
Peptide
Semaglutide
Outcome
Decrease3-point MACE
Study
n = 83,215
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
MACE rate was reduced with subcutaneous semaglutide (RR 0.74, 95% CI 0.58 to 0.94)
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779701
02HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, oral semaglutide significantly reduced MACE compared with placebo.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, oral semaglutide lowered major heart events compared with placebo.
Peptide
Semaglutide
Outcome
Decrease3-point MACE
Study
n = 83,215
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
tirzepatide, oral semaglutide, liraglutide, and dulaglutide were also significantly reduced compared with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779702
03HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, tirzepatide significantly reduced MACE compared with placebo.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, tirzepatide lowered major heart events compared with placebo.
Peptide
Tirzepatide
Outcome
Decrease3-point MACE
Study
n = 83,215
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
tirzepatide, oral semaglutide, liraglutide, and dulaglutide were also significantly reduced compared with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779703
04HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, liraglutide significantly reduced MACE compared with placebo.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, liraglutide lowered major heart events compared with placebo.
Peptide
Liraglutide
Outcome
Decrease3-point MACE
Study
n = 83,215
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
tirzepatide, oral semaglutide, liraglutide, and dulaglutide were also significantly reduced compared with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779704
05HumanSystematic reviewEfficacy outcome
In the MACE network, subcutaneous semaglutide ranked first of the regimens (P-score 0.87).
In plain wordsFor major heart events, semaglutide injections ranked first among the GLP-1 drugs compared.
Peptide
Semaglutide
Outcome
Not applicableMACE ranking (P-score)
Study
n = 83,215
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
Top ranked were subcutaneous semaglutide (P-score 0.87)
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779705
06HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, semaglutide did not significantly reduce all-cause or CV death compared with placebo.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, semaglutide did not clearly lower deaths compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeAll-cause and cardiovascular death
Study
n: not reported in source
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
No regimen significantly reduced all-cause or CV death compared with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779706
07HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, tirzepatide did not significantly reduce all-cause or CV death compared with placebo.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, tirzepatide did not clearly lower deaths compared with placebo.
Peptide
Tirzepatide
Outcome
No significant changeAll-cause and cardiovascular death
Study
n: not reported in source
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
No regimen significantly reduced all-cause or CV death compared with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779707
08HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, liraglutide did not significantly reduce all-cause or CV death compared with placebo.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, liraglutide did not clearly lower deaths compared with placebo.
Peptide
Liraglutide
Outcome
No significant changeAll-cause and cardiovascular death
Study
n: not reported in source
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
No regimen significantly reduced all-cause or CV death compared with placebo.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779708
09HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, tirzepatide reduced stroke versus placebo (RR 0.71).
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, tirzepatide lowered stroke compared with placebo.
Peptide
Tirzepatide
Outcome
DecreaseStroke
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Stroke was reduced with tirzepatide (RR 0.71, 95% CI 0.54 to 0.93)
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779709
10HumanSystematic reviewSafety outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, discontinuation was higher with subcutaneous semaglutide.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, more people stopped treatment with semaglutide injections.
Peptide
Semaglutide
Outcome
IncreaseDiscontinuation
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779710
11HumanSystematic reviewSafety outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, discontinuation was higher with oral semaglutide.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, more people stopped treatment with oral semaglutide.
Peptide
Semaglutide
Outcome
IncreaseDiscontinuation
Study
n: not reported in source
Outcome group
Adverse events · Whole body
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779711
12HumanSystematic reviewSafety outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, gastrointestinal discontinuation was higher with subcutaneous semaglutide.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, more people stopped semaglutide injections because of stomach side effects.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal discontinuation
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated · subcutaneousAs given in this study (human).
Source sentences
Summary
Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779712
13HumanSystematic reviewSafety outcome
In adults with type 2 diabetes and cardiovascular disease or high risk, gastrointestinal discontinuation was higher with oral semaglutide.
In plain wordsIn adults with type 2 diabetes and heart disease or high heart risk, more people stopped oral semaglutide because of stomach side effects.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal discontinuation
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650.
2 context sentences(design, population, supporting numbers)
Summary · context
The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain.
Summary · context
Eleven trials (n=83,215) were included.
Report a problemFND-4196779713

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

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.

Versions 5 to 7Current
27 Oct 2026, 16:36 UTC
The same notice was added 3 times, first on 21 Oct 2026, 18:59 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 4
12 Oct 2026, 12:10 UTC
Study results updated
Versions 2 to 3
9 Oct 2026, 03:07 UTC
The same notice was added 2 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC