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Study · Systematic review · 2026

3 results

Effect of Medications for Type 2 Diabetes on Cardiovascular Events and Mortality: A Comprehensive Pairwise and Network Meta-Analysis.

Silverii GA, Velardi V, Marinelli C, Lax A, Monami M, Mannucci E

Diabetes, obesity & metabolism30 Jul 2026Cited by 1 (Europe PMC)

PMID42530338 (opens in a new tab)PMCIDPMC13538750 (opens in a new tab)DOI10.1111/dom.71128 (opens in a new tab)PepBankPUB-42530338
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Summary

AimTo assess the effect of all the approved classes of medications for type 2 diabetes on Major Adverse Cardiovascular events (MACE) and all-cause mortality.MethodsWe performed a pairwise and network meta-analysis, including randomised controlled trials with a duration of at least 40 weeks, comparing medications versus placebo or an active comparator, in which MACE and deaths were adjudicated.ResultsWe included 93 studies. In pairwise meta-analyses, versus all comparators, GLP-1 receptor agonists (GLP1RA), SGLT-2 inhibitors (SGLT2i), metformin and pioglitazone were associated with a significant reduction of MACE and sulfonylureas with increased MACE. Furthermore, tirzepatide, SGLT2i and GLP1RA were associated with a significantly reduced all-cause mortality. In the principal (frequentist) network meta-analysis, metformin (OR 0.69, 95% CI 0.53-0.89), SGLT2i (0.82, 0.75-0.90), GLP1RA (0.87, 0.83-0.92) and tirzepatide (0.82, 0.72-0.93) were associated with a significant reduction of MACE versus placebo; no effect was observed for insulin, DPP4 inhibitors (DPP4i) or sulfonylureas. Tirzepatide (0.72, 0.64-0.82), SGLT2i (0.85, 0.80-0.91) and GLP1RA (0.85, 0.80-0.91) were associated with a significantly reduced mortality versus placebo; no effect was detected for other drugs. The sensitivity (Bayesian) analysis did not confirm the significance of results for pioglitazone on MACE. The certainty of evidence was moderate-to-high for GLP1RA, SGLT2i, Tirzepatide, DPP4i; low for metformin; low-to-moderate for other drugs.ConclusionSGLT2i, GLP1RA, tirzepatide and (with lower quality of evidence) pioglitazone and metformin are associated with a reduced incidence of cardiovascular events; tirzepatide, SGLT2i and GLP1RA are also associated with a reduced all-cause mortality.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, pairwise meta-analysis showed tirzepatide was associated with significantly reduced all-cause mortality versus all comparators.

    In plain wordsIn adults with type 2 diabetes, trials combined showed fewer deaths from any cause with tirzepatide than with the comparison treatments.

    Peptide
    Tirzepatide
    Outcome
    DecreaseAll-cause mortality, pairwise meta-analysis
    Study

    n: not reported in source

    Comparator
    All comparators
    Outcome group
    Mortality · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Furthermore, tirzepatide, SGLT2i and GLP1RA were associated with a significantly reduced all-cause mortality.
    2 context sentences
    Summary · context
    We performed a pairwise and network meta-analysis, including randomised controlled trials with a duration of at least 40 weeks, comparing medications versus placebo or an active comparator, in which MACE and deaths were adjudicated.
    Summary · context
    We included 93 studies.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, tirzepatide was associated with a significant reduction of MACE versus placebo in the network meta-analysis.

    In plain wordsIn adults with type 2 diabetes, tirzepatide was linked to fewer serious heart events than placebo in combined trial analysis.

    Peptide
    Tirzepatide
    Outcome
    DecreaseMACE versus placebo, network meta-analysis
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    OR
    0.82 ratio
    MACE versus placebo

    Source sentences

    Summary
    tirzepatide (0.82, 0.72-0.93) were associated with a significant reduction of MACE versus placebo
    2 context sentences
    Summary · context
    We performed a pairwise and network meta-analysis, including randomised controlled trials with a duration of at least 40 weeks, comparing medications versus placebo or an active comparator, in which MACE and deaths were adjudicated.
    Summary · context
    We included 93 studies.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with type 2 diabetes, tirzepatide was associated with significantly reduced mortality versus placebo in the network meta-analysis.

    In plain wordsIn adults with type 2 diabetes, tirzepatide was linked to fewer deaths than placebo in combined trial analysis.

    Peptide
    Tirzepatide
    Outcome
    DecreaseAll-cause mortality versus placebo, network meta-analysis
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Mortality · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    OR
    0.72 ratio
    mortality versus placebo

    Source sentences

    Summary
    Tirzepatide (0.72, 0.64-0.82), SGLT2i (0.85, 0.80-0.91) and GLP1RA (0.85, 0.80-0.91) were associated with a significantly reduced mortality versus placebo; no effect was detected for other drugs.
    2 context sentences
    Summary · context
    We performed a pairwise and network meta-analysis, including randomised controlled trials with a duration of at least 40 weeks, comparing medications versus placebo or an active comparator, in which MACE and deaths were adjudicated.
    Summary · context
    We included 93 studies.

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.

  1. Version 2Current

    12 Oct 2026, 12:10 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:07 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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