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The objective of this study was to explore the association between use of metformin or other antidiabetic drugs, diabetes, and the risk of pancreatic cancer.We conducted a case–control study using the UK-based General Practice Research Database (GPRD). Cases had a first-time diagnosis of pancreatic cancer, and six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the GPRD before the index date. Results were further adjusted in multivariate logistic regression analyses for potential confounders such as body mass index, smoking, alcohol consumption, and diabetes duration.In all, 2,763 case patients with a recorded diagnosis of pancreatic cancer were identified. Mean age±s.d. was 69.5±11.0 years. Long-term use (≥30 prescriptions) of metformin was not associated with a materially altered risk of pancreatic cancer (adjusted odds ratio (adj. OR): 0.87, 95% confidence interval (CI): 0.59–1.29), but there was a suggestion of effect modification by gender, as long-term use of metformin was linked to a decreased risk in women (adj. OR: 0.43, 95% CI: 0.23–0.80). Both use of sulfonylureas (≥30 prescriptions, adj. OR: 1.90, 95% CI: 1.32–2.74) and of insulin (≥40 prescriptions, adj. OR: 2.29, 95% CI: 1.34–3.92) were associated with an increased risk of pancreatic cancer.Use of metformin was associated with a decreased risk of pancreatic cancer in women only, whereas use of sulfonylureas and of insulin was associated with an increased risk of pancreatic cancer.