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

Abstract

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 everusers 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.

Risk factors for development of diabetes mellitus (Type 3c) after partial pancreatectomy: A systematic review

“…There is some evidence that metformin has been associated with a significant reduction in cancer risk, although this has only been demonstrated in the setting of de novo cancer development . A recent retrospective cohort study demonstrated an association with significantly reduced mortality with metformin use in patients with diabetes post pancreatitis but this was not significant in the group post pancreatic surgery . Although there are no studies specific to the type 3c DM population, oral hypoglycaemic agents known to cause pancreatitis such as GLP‐1 agonists should be used with caution in this population with reduced residual pancreatic volume and recent instrumentation until further data is available to clarify if there is any increased risk of pancreatitis .…”

Relationships are between metformin use and survival in pancreatic cancer patients concurrent with diabetes

“…New studies in recent years are springing up to clarify the question. [ 11 , 12 ] Therefore, here we perform a meta-analysis to assess the effect of metformin on survival outcome of pancreatic cancer patients with concurrent diabetes mellitus.…”

Use of Insulin and the Risk of Progression of Pancreatitis: A Population‐Based Cohort Study

“…Although insulin is often administered for glycemic control in AP, 10,11 there is a dearth of evidence on the association between new use of insulin and risk of progression from AP to RAP and CP. To date, there is only indirect evidence-a 2017 population-based study from the United Kingdom followed 31,789 individuals with diabetes after AP or CP (individuals with progression from AP to CP were not specifically investigated) while considering insulin use as an end point, not an exposure.…”