GLP-1 Evidence

Not medical advice. A record of published research and our assessments of it. The limits

The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis

Design
Retrospective cohort · 1321056 participants · Hard outcome
Match to healthy normal-weight adults aged 55–75
Partial matchNot restricted to diabetes or obesity and effects consistent in subgroups without them; but a substance-use-disorder population and observational.
Could weight loss explain it?
UnlikelyEffect consistent regardless of comorbid obesity or diabetes, arguing against weight mediation; confounding by prescribing patterns remains.
Study tier
Study tier 3Large observational cohort with plausible confounding.
Assessment
Version 2 · curated · Sep 13, 2026

Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.

In US health-system records, people with opioid or alcohol use disorder who were prescribed GLP-1/GIP drugs had 40-50% lower rates of overdose and alcohol intoxication, regardless of whether they had diabetes or obesity. Observational, but one of the few signals that does not depend on metabolic disease.

01Findings

What the study reported

Drugs
Class unspecified, Tirzepatide
Primary outcome
Opioid overdose in OUD; alcohol intoxication in AUD (EHR, 136 US health systems)
Effect
aIRR 0.60 (opioid overdose); aIRR 0.50 (alcohol intoxication); consistent across diabetes/obesity subgroups
95% confidence interval
0.43 to 0.83; 0.40 to 0.63
Follow-up
18 years
Adverse events
Not extracted
Limitations
Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.

Who was studied

Obesity status
mixed; subgroups with and without obesity
Diabetes status
mixed
Baseline condition
opioid or alcohol use disorder
Sample size
747

Study quality details

Study design
Retrospective cohort
Sample size
747
Randomization
no
Blinding
not stated
Comparator
not stated
Follow up duration
18 years
Outcome type
unknown
Replication
not assessed (auto)
Consistency with other evidence
not assessed (auto)
Population applicability
INDIRECT
Statistical precision
CI reported: 95% confidence interval (CI
Risk of bias
confounding by indication; exposure defined as any prescription
Funding conflicts
unclear
Peer review status
yes
02Funding

Funding and conflicts

Funding
None declared
Industry funded
No
Manufacturer
None identified
Sponsor role
not reported in abstract
Author conflicts
None.
Independent replication
unknown

Funding is shown on every study and never used to score it.

03Claims

Claims this study bears on

04Source

The source, as retrieved

Abstract

[AIMS] This study aimed to estimate the strength of association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RA) and the incidence of opioid overdose and alcohol intoxication in patients with opioid use disorder (OUD) and alcohol use disorder (AUD), respectively. This study also aimed to compare the strength of the GIP/GLP-1 RA and substance use-outcome association among patients with comorbid type 2 diabetes and obesity. [DESIGN] A retrospective cohort study analyzing de-identified electronic health record data from the Oracle Cerner Real-World Data. [SETTING] About 136 United States of America health systems, covering over 100 million patients, spanning January 2014 to September 2022. [PARTICIPANTS] The study included 503 747 patients with a history of OUD and 817 309 patients with a history of AUD, aged 18 years or older. [MEASUREMENTS] The exposure indicated the presence (one or more) or absence of GIP/GLP-1 RA prescriptions. The outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort. Potential confounders included comorbidities and demographic factors. [FINDINGS] Patients with GIP/GLP-1 RA prescriptions demonstrated statistically significantly lower rates of opioid overdose [adjusted incidence rate ratio (aIRR) in OUD patients: 0.60; 95% confidence interval (CI) = 0.43-0.83] and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI = 0.40-0.63) compared to those without such prescriptions. When stratified by comorbid conditions, the rate of incident opioid overdose and alcohol intoxication remained similarly protective for those prescribed GIP/GLP-1 RA among patients with OUD and AUD. [CONCLUSIONS] Prescriptions of glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonists appear to be associated with lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder and alcohol use disorder. The protective effects are consistent across various subgroups, including patients with comorbid type 2 diabetes and obesity.

Where this record came from

SourceRetrievedIdentifier
pubmedSep 13, 202639415416
first ingestion