Antidiabetic Medications and Mortality Risk in Individuals With Pancreatic Cancer-Related Diabetes and Postpancreatitis Diabetes: A Nationwide Cohort Study

摘要

OBJECTIVE There are no specific treatment guidelines for diabetes of the exocrine pancreas. High-quality studies are warranted to investigate whether the use of antidiabetic medications has survival benefit in individuals with diabetes of the exocrine pancreas. The objective was to determine the risk of mortality associated with the use of antidiabetic medications in individuals with pancreatic cancer-related diabetes (PCRD) and postpancreatitis diabetes mellitus (PPDM). RESEARCH DESIGN AND METHODS Nationwide pharmaceutical dispensing data (2006-2015) linked to hospital discharge data were used to identify 1,862 individuals with PCRD or PPDM. Multivariable Cox regression analysis was conducted, and the risk was expressed as hazard ratios and 95% CIs. A 6-month lag was used to minimize reverse causality. RESULTS In individuals with PCRD, ever users of metformin (adjusted hazard ratio 0.54; 95% CI 0.46-0.63) and ever users of insulin (adjusted hazard ratio 0.46; 95% CI 0.39-0.55) had significantly lower risks of mortality compared with never users of antidiabetic medications. These associations attenuated toward the null with the use of a 6-month lag. In individuals with PPDM, ever users of metformin had a significantly lower risk of mortality (adjusted hazard ratio 0.51; 95% CI 0.36-0.70), whereas ever-users of insulin did not have a significantly changed risk of mortality (adjusted hazard ratio 0.75; 95% CI 0.49-1.14) compared with never users of antidiabetic medications. The former association remained significant with the use of a 6-month lag. CONCLUSIONS Metformin promotes a survival benefit in individuals with PPDM but not PCRD. Reverse causality may play a role in the association between insulin use and mortality in PCRD.