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Study · Observational study · n = 20,198 · 2026

6 results

Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach.

Henney AE, Riley DR, Heague M, Roberts CA, Hydes TJ, Anson M, Hughes DM, Alam U, Cuthbertson DJ

Diabetes, obesity & metabolism7 Oct 2025Cited by 6 (Europe PMC)

PMID41058240 (opens in a new tab)PMCIDPMC12673470 (opens in a new tab)DOI10.1111/dom.70169 (opens in a new tab)PepBankPUB-41058240
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Summary

AimsThere is growing evidence that the GLP-1 system is implicated in alcohol and other substance use disorders, and that GLP-1-based therapies may have therapeutic relevance in alcohol use disorder (AUD). We aimed to determine the impact of GLP-1 based therapies on incident AUDs in a real-world setting in patients with T2D.Material and methodsWe conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America. Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i). First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses. Four target trial cohorts were generated and compared with a reference arm of patients treated with DPP4i: cohort (1) treatment with tirzepatide; cohort (2) treatment with semaglutide; cohort (3) treatment with liraglutide; and cohort (4) treatment with dulaglutide. Cohorts underwent propensity score matching 1:1 for confounders. We examined rates of incident AUD (ICD-10 code F10) and performed head-to-head analyses of the incretin-based therapies. We also performed sensitivity analyses relating to whether treatment was adjunctive therapy with metformin and by treatment adherence.ResultsAfter propensity-score matching, we identified four target trials of patients treated with tirzepatide (n = 7165), semaglutide (n = 20 198), liraglutide (n = 6565), and dulaglutide (n = 19 061); 1:1 with the reference (DPP4i) patients. Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively). Head-to-head comparison revealed tirzepatide had a significant risk reduction compared to liraglutide in incident AUD (0.47 [0.24, 0.92]).ConclusionIn patients with T2D, tirzepatide and semaglutide treatment is associated with a lower incidence of AUD; robust randomised, controlled evidence for the use of these drugs for this novel indication is appropriate.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanObservational studyEfficacy outcome

    In patients with diabetes, semaglutide was linked to lower incident alcohol-use disorder than DPP4 inhibitors (HR 0.68).

    In plain wordsIn patients with diabetes, semaglutide use was linked to fewer new alcohol-use disorders than DPP4 inhibitor use.

    Peptide
    Semaglutide
    Outcome
    DecreaseIncident alcohol-use disorder
    Study

    n = 20,198

    Comparator
    DPP4 inhibitors
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    0.68
    semaglutide versus DPP4 inhibitors
    95% CI lower
    0.52
    hazard ratio
    95% CI upper
    0.89
    hazard ratio

    Source sentences

    Summary
    Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively).
    3 context sentences
    Summary · context
    We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America.
    Summary · context
    Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i).
    Summary · context
    First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses.
  2. 02HumanObservational studyEfficacy outcome

    In patients with diabetes, dulaglutide showed no significant reduction in incident alcohol-use disorder versus DPP4 inhibitors.

    In plain wordsIn patients with diabetes, dulaglutide use showed no significant reduction in new alcohol-use disorders compared with DPP4 inhibitor use.

    Peptide
    Dulaglutide (Trulicity)
    Outcome
    No significant changeIncident alcohol-use disorder
    Study

    n = 19,061

    Comparator
    DPP4 inhibitors
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively).
    3 context sentences
    Summary · context
    We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America.
    Summary · context
    Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i).
    Summary · context
    First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses.
  3. 03HumanObservational studyEfficacy outcome

    In patients with diabetes, tirzepatide was linked to lower incident alcohol-use disorder than DPP4 inhibitors (HR 0.47).

    In plain wordsIn patients with diabetes, tirzepatide use was linked to fewer new alcohol-use disorders than DPP4 inhibitor use.

    Peptide
    Tirzepatide
    Outcome
    DecreaseIncident alcohol-use disorder
    Study

    n = 7,165

    Comparator
    DPP4 inhibitors
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    0.47
    tirzepatide versus DPP4 inhibitors
    95% CI lower
    0.29
    hazard ratio
    95% CI upper
    0.75
    hazard ratio

    Source sentences

    Summary
    Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively).
    3 context sentences
    Summary · context
    We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America.
    Summary · context
    Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i).
    Summary · context
    First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses.
  4. 04HumanObservational studyEfficacy outcome

    In patients with diabetes, liraglutide showed no significant reduction in incident alcohol-use disorder versus DPP4 inhibitors.

    In plain wordsIn patients with diabetes, liraglutide use showed no significant reduction in new alcohol-use disorders compared with DPP4 inhibitor use.

    Peptide
    Liraglutide
    Outcome
    No significant changeIncident alcohol-use disorder
    Study

    n = 6,565

    Comparator
    DPP4 inhibitors
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively).
    3 context sentences
    Summary · context
    We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America.
    Summary · context
    Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i).
    Summary · context
    First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses.
  5. 05HumanObservational studyEfficacy outcome

    In patients with diabetes, tirzepatide was linked to lower incident alcohol-use disorder than liraglutide (HR 0.47).

    In plain wordsIn patients with diabetes, tirzepatide use was linked to fewer new alcohol-use disorders than liraglutide use.

    Peptide
    Tirzepatide
    Outcome
    DecreaseIncident alcohol-use disorder
    Study

    n: not reported in source

    Comparator
    Liraglutide
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    0.47
    tirzepatide versus liraglutide, head-to-head
    95% CI lower
    0.24
    hazard ratio
    95% CI upper
    0.92
    hazard ratio

    Source sentences

    Summary
    Head-to-head comparison revealed tirzepatide had a significant risk reduction compared to liraglutide in incident AUD (0.47 [0.24, 0.92]).
    3 context sentences
    Summary · context
    We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America.
    Summary · context
    Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i).
    Summary · context
    First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses.
  6. 06HumanObservational studyEfficacy outcome

    In patients with diabetes, liraglutide was linked to higher incident alcohol-use disorder than tirzepatide in the head-to-head comparison.

    In plain wordsIn patients with diabetes, liraglutide use was linked to more new alcohol-use disorders than tirzepatide use.

    Peptide
    Liraglutide
    Outcome
    IncreaseIncident alcohol-use disorder
    Study

    n: not reported in source

    Comparator
    Tirzepatide
    Outcome group
    Addiction, withdrawal and alcohol intake · Mental health and mood
    Studied dose
    Dose not stated

    Measurements

    Hazard ratio
    0.47
    tirzepatide versus liraglutide, head-to-head
    95% CI lower
    0.24
    hazard ratio
    95% CI upper
    0.92
    hazard ratio

    Source sentences

    Summary
    Head-to-head comparison revealed tirzepatide had a significant risk reduction compared to liraglutide in incident AUD (0.47 [0.24, 0.92]).
    3 context sentences
    Summary · context
    We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America.
    Summary · context
    Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i).
    Summary · context
    First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses.

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 5Current

    22 Oct 2026, 02:25 UTC

    Study results updated

  2. Versions 2 to 4

    21 Oct 2026, 18:59 UTC

    The same notice was added 3 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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