Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials.

Lee MMY, Sattar N, Pop-Busui R, Deanfield J, Emerson SS, Inzucchi SE, Mann JFE, Marx N, Mulvagh SL, Poulter NR, Badve SV, Pratley RE, Perkovic V, Buse JB, McGuire DK

Diabetes care1 May 2025Cited by 100 (Europe PMC)

PMID40156846DOI10.2337/dc25-0241PepBankPUB-40156846

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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 study9

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone9

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.

01HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) reduced MACE by 14% (HR 0.86) versus placebo.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, cut major heart events by 14% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseMajor adverse cardiovascular events (MACE)
Study
n = 71,351
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.86 ratio
MACE
Source sentences
Summary
Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%).
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684601
02HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) reduced hospitalization for heart failure by 14% (HR 0.86) versus placebo.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, cut heart-failure hospital stays by 14% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseHospitalization for heart failure
Study
n = 71,351
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Measurements
HR
0.86 ratio
hospitalization for heart failure
Source sentences
Summary
Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%).
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684602
03HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) reduced the composite kidney outcome by 17% (HR 0.83) versus placebo.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, cut serious kidney events by 17% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseComposite kidney outcome
Study
n = 71,351
Comparator
Placebo
Outcome group
Kidney function · Kidney and urinary
Measurements
HR
0.83 ratio
composite kidney outcome
Source sentences
Summary
Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%).
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684603
04HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) reduced all-cause mortality by 12% (HR 0.88) versus placebo.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, cut deaths from any cause by 12% compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseAll-cause mortality
Study
n = 71,351
Comparator
Placebo
Outcome group
Mortality · Cardiovascular
Measurements
HR
0.88 ratio
all-cause mortality
Source sentences
Summary
Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%).
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684604
05HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) did not increase the risk of severe hypoglycemia.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, did not raise the risk of severe low blood sugar.
Peptide
Semaglutide
Outcome
No significant changeSevere hypoglycemia
Study
n = 71,351
Comparator
Placebo
Outcome group
Adverse events · Metabolic and weight
Source sentences
Summary
There were no increased risks of severe hypoglycemia, retinopathy, or pancreatic events.
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684607
06HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) did not increase the risk of retinopathy.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, did not raise the risk of eye retinopathy.
Peptide
Semaglutide
Outcome
No significant changeRetinopathy
Study
n = 71,351
Comparator
Placebo
Outcome group
Adverse events · Eye
Source sentences
Summary
There were no increased risks of severe hypoglycemia, retinopathy, or pancreatic events.
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684608
07HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) did not increase the risk of pancreatic events.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, did not raise the risk of pancreas problems.
Peptide
Semaglutide
Outcome
No significant changePancreatic events
Study
n = 71,351
Comparator
Placebo
Outcome group
Adverse events · Gastrointestinal
Source sentences
Summary
There were no increased risks of severe hypoglycemia, retinopathy, or pancreatic events.
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684609
08HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled long-acting GLP-1RA (including semaglutide) gave a consistent 14% reduction for all MACE components.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs, including semaglutide, lowered each type of major heart event by about 14%.
Peptide
Semaglutide
Outcome
DecreaseMACE components
Study
n: not reported in source
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
A consistent 14% reduction was seen for all MACE components.
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684605
09HumanNot a test of Semaglutide aloneSystematic reviewOther
In adults with type 2 diabetes, there was no significant heterogeneity of GLP-1RA effects between subcutaneous and oral routes.
In plain wordsIn adults with type 2 diabetes, long-acting GLP-1 drugs showed no clear difference in effect between injected and oral forms.
Peptide
Semaglutide
Outcome
No significant changeHeterogeneity by administration route
Study
n: not reported in source
Comparator
Subcutaneous versus oral
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
There was no significant heterogeneity by GLP-1RA administration route (subcutaneous vs. oral).
2 context sentences(design, population, supporting numbers)
Summary · context
In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinet…
Summary · context
Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included.
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.
Report a problemFND-4015684606

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 2Current
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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