Sabrina Brinkmöller, Regina Poß-Doering, Cornelia Straßner, Gunter Laux Department of Primary Care and Health Services Research, Heidelberg University, Medical Faculty, Heidelberg University Hospital, Heidelberg, GermanyCorrespondence: Sabrina Brinkmöller, Department of Primary Care and Health Services Research, Heidelberg University, Medical Faculty, Heidelberg University Hospital, Im Neuenheimer Feld 130.3, Heidelberg, 69120, Germany, Email Sabrina.Brinkmoeller@med.uni-heidelberg.deBackground: Chronic non-cancer pain is common in primary care and may be managed with long-term opioid therapy. The German guideline “Long-term Use of Opioids for Chronic Non-Cancer Pain” provides recommendations for such treatment. The role of opioid formulation (long-acting vs. short-acting) and the association with opioid-related disorders remains underexplored. This study aims to explore associations between opioid formulation and opioid-related disorders in patients with chronic non-cancer pain receiving long-term opioid therapy in German general practices.Methods: We conducted a retrospective cross-sectional claims data analysis using data from one statutory health insurer in Baden-Württemberg (AOK), Germany, for the year 2021. The analysis included patients aged ≥ 18 years who received at least one oral or transdermal opioid prescription in all four quarters. Exclusion criteria were malignant diseases or palliative care. The outcome was opioid-related disorder (ICD-10 category F11.-). Multivariable logistic regression analyses were performed to identify predictors.Results: Multiple models were calculated. The main model included a total of 34,205 patients. The mean age was 70 years, and 65% were female. Overall, 3.1% of patients were diagnosed with an opioid-related disorder. Weak opioids were most frequently prescribed. Long-acting opioids predominated. Higher odds of opioid-related disorders were observed in patients with substance use disorders involving such as sedatives (OR = 5.6, 95% CI: 4.48– 7.01) or alcohol (OR = 2.2, 95% CI: 1.82– 2.66). Short-acting opioids (OR = 2.0, 95% CI: 1.53– 2.48) and combined long- and short-acting therapy (OR = 3.5, 95% CI: 2.38– 5.00) were associated with higher odds of opioid-related disorders compared with long-acting opioids (all p < 0.001).Conclusion: The results suggest that short-acting opioids, either alone or as part of combination therapy, may be more strongly associated with opioid-related disorders in patients with chronic non-cancer pain and long-term opioid therapy than long-acting opioids alone. Further research is needed to clarify these relationships and their underlying causes.Keywords: chronic non-cancer pain, primary care, general practice, long-term opioid therapy, opioid-related disorders, opioid formulation, long-acting opioids, short-acting opioids, Germany