Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis.

Alfayez OM, Almohammed OA, Alkhezi OS, Almutairi AR, Al Yami MS

Cardiovascular diabetology22 Jun 2020Cited by 31 (Europe PMC)

PMID32571416PMCIDPMC7310317DOI10.1186/s12933-020-01070-zPepBankPUB-32571416

Summary

BackgroundThe cardiovascular outcome trials (CVOTs) have shown that glucagon like peptide-1 receptor agonists (GLP1RAs) have varying degrees of cardiovascular (CV) safety in patients with type 2 diabetes mellitus (T2DM.) The lack of any head-to-head comparative trials among GLP1RAs urged the need for an indirect comparison of these agents. Therefore, this study was conducted to indirectly compare the CV safety and mortality effects among different GLP1RAs in patients with T2DM using network meta-analysis (NMA).MethodsMedline was searched to identify GLP1RA CVOTs to date. The outcomes of interest were CV death, myocardial infarction (IM), stroke, and death from any cause. An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. This NMA was reported in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA).ResultsA total of seven GLP1RA CVOTs were included having 56,004 patients. The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events.ConclusionThe GLP1RAs have shown significant benefits in terms of CV safety. The indirect comparison and ranking probability results have shown that one weekly semaglutide and oral semaglutide seems to be the preferred option in patients with T2DM and established or at high risk of CVD. This result can aid health care providers, pharmacy and therapeutics committees in hospitals, and insurance companies when deciding which GLP1RA to start or add to their formulary.

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

Results from this study11

8 results from studies that gave the peptide. 8 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes in a network meta-analysis, oral semaglutide reduced CV death more than exenatide.
In plain wordsIn adults with type 2 diabetes, indirect comparison found fewer cardiovascular deaths with oral semaglutide than with exenatide.
Peptide
Semaglutide
Outcome
DecreaseCV death, oral semaglutide versus exenatide
Study
n: not reported in source
Comparator
Exenatide
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Measurements
OR
0.47 odds ratio
oral semaglutide vs exenatide
95% CI
0.21 to 0.99 OR
oral semaglutide vs exenatide
Source sentences
Summary
The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141601
02HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes in a network meta-analysis, oral semaglutide reduced CV death more than dulaglutide.
In plain wordsIn adults with type 2 diabetes, indirect comparison found fewer cardiovascular deaths with oral semaglutide than with dulaglutide.
Peptide
Semaglutide
Outcome
DecreaseCV death, oral semaglutide versus dulaglutide
Study
n: not reported in source
Comparator
Dulaglutide
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Measurements
OR
0.46 odds ratio
oral semaglutide vs dulaglutide
95% CI
0.2 to 0.97 OR
oral semaglutide vs dulaglutide
Source sentences
Summary
The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141602
03HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes in a network meta-analysis, oral semaglutide reduced CV death more than albiglutide.
In plain wordsIn adults with type 2 diabetes, indirect comparison found fewer cardiovascular deaths with oral semaglutide than with albiglutide.
Peptide
Semaglutide
Outcome
DecreaseCV death, oral semaglutide versus albiglutide
Study
n: not reported in source
Comparator
Albiglutide
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Measurements
OR
0.45 odds ratio
oral semaglutide vs albiglutide
95% CI
0.19 to 0.97 OR
oral semaglutide vs albiglutide
Source sentences
Summary
The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141603
04HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes in a network meta-analysis, oral semaglutide reduced CV death more than lixisenatide.
In plain wordsIn adults with type 2 diabetes, indirect comparison found fewer cardiovascular deaths with oral semaglutide than with lixisenatide.
Peptide
Semaglutide
Outcome
DecreaseCV death, oral semaglutide versus lixisenatide
Study
n: not reported in source
Comparator
Lixisenatide
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Measurements
OR
0.43 odds ratio
oral semaglutide vs lixisenatide
95% CI
0.19 to 0.92 OR
oral semaglutide vs lixisenatide
Source sentences
Summary
The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141604
05HumanSystematic reviewEfficacy outcome
In the network meta-analysis, oral semaglutide had the highest probability of ranking first for reducing CV death.
In plain wordsIn an indirect comparison of GLP-1 drugs, oral semaglutide was most likely to rank first for lowering cardiovascular death.
Peptide
Semaglutide
Outcome
DecreaseRank probability for reducing CV death, oral semaglutide
Study
n: not reported in source
Comparator
Other GLP1RAs in the network
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141605
06HumanSystematic reviewEfficacy outcome
In the network meta-analysis, oral semaglutide had the highest probability of ranking first for reducing death from any cause.
In plain wordsIn an indirect comparison of GLP-1 drugs, oral semaglutide was most likely to rank first for lowering deaths from any cause.
Peptide
Semaglutide
Outcome
DecreaseRank probability for reducing death from any cause, oral semaglutide
Study
n: not reported in source
Comparator
Other GLP1RAs in the network
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated · oralAs given in this study (human).
Source sentences
Summary
The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141606
07HumanSystematic reviewEfficacy outcome
In the network meta-analysis, once-weekly semaglutide had the highest probability of ranking first for reducing myocardial infarction.
In plain wordsIn an indirect comparison of GLP-1 drugs, weekly semaglutide was most likely to rank first for lowering heart attacks.
Peptide
Semaglutide
Outcome
DecreaseRank probability for reducing myocardial infarction, once-weekly semaglutide
Study
n: not reported in source
Comparator
Other GLP1RAs in the network
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141607
08HumanSystematic reviewEfficacy outcome
In the network meta-analysis, once-weekly semaglutide had the highest probability of ranking first for reducing stroke.
In plain wordsIn an indirect comparison of GLP-1 drugs, weekly semaglutide was most likely to rank first for lowering strokes.
Peptide
Semaglutide
Outcome
DecreaseRank probability for reducing stroke, once-weekly semaglutide
Study
n: not reported in source
Comparator
Other GLP1RAs in the network
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
Show in the study text Report a problemFND-3257141608

Studies that did not test the peptide alone3

In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semaglutide.

09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In the network meta-analysis, most GLP1RA treatments did not differ significantly from each other in death from any cause.
In plain wordsIn an indirect comparison, most GLP-1 drugs did not differ significantly from each other in deaths from any cause.
Peptide
Semaglutide
Outcome
No significant changeDeath from any cause across GLP1RAs
Study
n: not reported in source
Comparator
Other GLP1RAs in the network
Outcome group
Mortality · Cardiovascular
Source sentences
Summary
No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3257141609
10HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In the network meta-analysis, most GLP1RA treatments did not differ significantly from each other in myocardial infarction.
In plain wordsIn an indirect comparison, most GLP-1 drugs did not differ significantly from each other in heart attacks.
Peptide
Semaglutide
Outcome
No significant changeMyocardial infarction across GLP1RAs
Study
n: not reported in source
Comparator
Other GLP1RAs in the network
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3257141610
11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In the network meta-analysis, most GLP1RA treatments did not differ significantly from each other in stroke.
In plain wordsIn an indirect comparison, most GLP-1 drugs did not differ significantly from each other in strokes.
Peptide
Semaglutide
Outcome
No significant changeStroke across GLP1RAs
Study
n: not reported in source
Comparator
Other GLP1RAs in the network
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events.
1 context sentence(design, population, supporting numbers)
Summary · context
A total of seven GLP1RA CVOTs were included having 56,004 patients.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-3257141611

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.

Version 3Current
21 Oct 2026, 18:59 UTC
Study data updated · source update from Europe PMC
Version 2
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis.

Summary

Results from this study11

Studies that did not test the peptide alone3

Version history

Subjects

Publication types

MeSH terms

Keywords