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.

چکیده اصلی

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Forte, Karolinska Institutet, and Region Stockholm.

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