Association of GLP-1 receptor agonists with alcohol use disorder-related and substance use disorder-related hospital admissions during treatment and after discontinuation: a Swedish register-based within-individual observational study.
GLP-1 receptor agonists were associated with lower rates of hospitalizations for alcohol use disorder during treatment and shortly after stopping, but the benefits for substance use disorder were not consistent.
Where it sits
this study against the rest of the exenatide corpusSummary and findings
This study investigated the association of GLP-1 receptor agonists with hospital admissions related to alcohol use disorder and substance use disorder among individuals with type 2 diabetes. A total of 167,026 individuals were analyzed, with 41,109 receiving GLP-1 receptor agonists. The study found that GLP-1 exposure was associated with lower rates of hospitalizations related to both disorders during treatment and shortly after discontinuation.
Abstract
<h4>Background</h4>Evidence suggests that GLP-1 receptor agonists might reduce substance use across different substance use disorders. However, data on substance use-related outcomes after GLP-1 discontinuation are absent. This study aimed to investigate the risk of alcohol and substance use-related hospitalisations during and after exposure to GLP-1 receptor agonists.<h4>Methods</h4>This within-individual observational study used Swedish registers to identify residents of Stockholm County with a first registered diagnosis of type 2 diabetes between Jan 1, 2005, and Dec 31, 2024 who had received GLP-1 receptor agonists and, for comparison, DPP-4 inhibitors. Active follow‑up started on Jan 1, 2015, or on the date of the first registered diabetes diagnosis, whichever occurred later. Patients were followed up until the end of the observation period (Dec 31, 2024). The main outcomes were hospitalisations related to alcohol use disorder and substance use disorder (which included the alcohol use disorder-related events). Fixed-effects Poisson regression models were used to estimate rate ratios (RRs) of hospitalisations, comparing periods of GLP-1 receptor agonist or DPP-4 inhibitor exposure and two post-exposure windows (days 1-182 and 183-364) with unexposed periods in the same individuals. People with lived experience were not involved in the study.<h4>Findings</h4>167 026 individuals with type 2 diabetes (mean age 63·98 years [SD 13·77]; median age 65·00 years [IQR 55·00-74·00]; 96 133 [57·6%] males and 70 893 [42·4%] females) were included in the study. Ethnicity data were unavailable. 1559 (0·9%) individuals had at least one alcohol use disorder-related hospitalisation and 2008 (1·2%) had at least one substance use disorder-related hospitalisation. 41 109 (24·6%) individuals received GLP-1 receptor agonists during the study period, and 23 666 (14·2%) received DPP-4 inhibitors. 308 (0·7%) of those receiving GLP-1 receptor agonists had at least one alcohol-related hospitalisation during the observational period, and 444 (1·1%) had at least one substance use-related hospitalisation; 957 (66·1%) of the 1447 substance use disorder-related hospitalisations recorded in these 444 individuals were attributed to alcohol use disorder. GLP-1 exposure was associated with lower rates of hospitalisations related to alcohol use disorder (RR 0·55, 95% CI 0·43-0·70) and substance use disorder (0·61, 0·50-0·74) compared with unexposed periods for the same individuals. For individuals with alcohol use disorder, the association with hospitalisation rate reduction persisted during days 1-182 after discontinuation of GLP-1 receptor agonists (0·70, 0·50-0·98) but was no longer evident during days 183-364 after discontinuation (1·07, 0·71-1·63); for substance use disorder, there were no statistically significant associations with reduction after discontinuation of GLP-1 receptor agonists (days 1-182: 0·79, 0·61-1·02; days 183-364: 0·89, 0·63-1·26). DPP-4 inhibitors were not associated with consistent rate reductions.<h4>Interpretation</h4>GLP-1 receptor agonist treatment was associated with lower rates of hospitalisation in individuals with alcohol use disorder and substance use disorder. This association extended into the first 182 days after discontinuation for alcohol use disorder but not for substance use disorder. Findings support clinical monitoring of substance use when GLP-1 receptor agonist treatment is stopped.<h4>Funding</h4>Forte, Karolinska Institutet, and Region Stockholm.
Background
This paper addresses the potential impact of GLP-1 receptor agonists on hospital admissions related to alcohol and substance use disorders in individuals with type 2 diabetes. Prior evidence suggested that GLP-1 receptor agonists might influence substance use behaviors, but data on outcomes following discontinuation were lacking. Understanding these associations is crucial for managing the health of patients with diabetes who may also struggle with substance use disorders.
Methods
This within-individual observational study utilized Swedish registers to identify residents of Stockholm County diagnosed with type 2 diabetes between January 1, 2005, and December 31, 2024. The study included 167,026 individuals, with active follow-up starting on January 1, 2015, or at the first diabetes diagnosis. The primary outcomes measured were hospitalizations related to alcohol use disorder and substance use disorder, analyzed using fixed-effects Poisson regression models.
Results
The primary finding indicated that GLP-1 receptor agonist exposure was associated with a reduced rate of alcohol use disorder-related hospitalizations (RR 0.55, 95% CI 0.43-0.70) compared to unexposed periods. Additionally, 308 individuals receiving GLP-1 had at least one alcohol-related hospitalization. The association persisted for 182 days post-discontinuation for alcohol use disorder (RR 0.70, 95% CI 0.50-0.98), but not for substance use disorder hospitalizations.
Interpretation
The results suggest that GLP-1 receptor agonists may be linked to lower hospitalization rates for alcohol use disorder, which is statistically significant but may not be clinically significant given the small effect size. The lack of sustained benefit for substance use disorder after discontinuation raises questions about the long-term implications of GLP-1 therapy. Confounding factors inherent in observational studies, such as unmeasured lifestyle variables, may limit the conclusions drawn from these findings.
Key findings
- 167,026 individuals with type 2 diabetes included, mean age 63.98 years (SD 13.77), n=167026.
- 1559 (0.9%) had at least one alcohol use disorder-related hospitalization, n=167026.
- 308 (0.7%) of those receiving GLP-1 receptor agonists had at least one alcohol-related hospitalization, n=41109.
- GLP-1 exposure associated with lower rates of alcohol use disorder hospitalizations (RR 0.55, 95% CI 0.43-0.70).
- For alcohol use disorder, the association with hospitalization rate reduction persisted during days 1-182 after discontinuation (RR 0.70, 95% CI 0.50-0.98).
- No statistically significant associations for substance use disorder hospitalizations after discontinuation (days 183-364: RR 0.89, 95% CI 0.63-1.26).
Limitations
- Observational study design may introduce confounding factors.
- Ethnicity data were unavailable.
- Follow-up after discontinuation was limited to 364 days.
- No consistent associations for substance use disorder after discontinuation.
- Potential for unmeasured variables affecting outcomes.