Elevated HbA1c Levels Are Associated with a Risk of Pancreatic Cancer: A Case-Control Study

Background: The early diagnosis of pancreatic cancer (ICD-10 C25) can improve the patient's prognosis. The association between pancreatic cancer and type 2 diabetes (T2D) is known, but not yet fully understood. It is, therefore, necessary to investigate the impact of hemoglobin A1c (HbA1c) serum levels on pancreatic cancer development and the potential intervention options. Methods: In the case-control study, patients from the German IQVIA^TM Disease Analyzer database aged ≥18 years with a diagnosis of pancreatic cancer (ICD-10 C25) and a diagnosis of T2D (ICD-10: E11) were included. The patients' propensity score matched 1:5 with individuals without pancreatic cancer. Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Results: An elevated serum HbA1c prior to the index date was found to be significantly associated with an increased risk of a subsequent pancreatic cancer diagnosis for the mean HbA1c values of 6.5-8.4% (OR: 1.38; 95% CI: 1.22-1.57) as well as for mean HbA1c values ≥8.5% (OR: 1.41; 95% CI: 1.16-1.73). The only antihyperglycemic agent negatively associated with the subsequent pancreatic cancer diagnosis was the sodium-glucose cotransporter-2 (SGLT-2) inhibitor, with an odds ratio of 0.80 (95% confidence interval: 0.74-0.87 per year of therapy). This correlation was observed in both age- and sex-stratified subgroups. Conclusions: The data indicate that elevated serum HbA1c levels in patients with T2D are associated with an increased risk of pancreatic cancer development. It is possible that SGLT2 therapy may prove an effective means of reducing the risk of pancreatic cancer, thereby offering a potential avenue for the future reduction in pancreatic cancer incidence in patients with T2D.