The coexistence of Pancreatic cancer (PC) with diabetes mellitus (DM) and metabolic disorders (MDs) may further exacerbate the disease burden; however, the long-term mortality trends remain unclear.

We utilized the CDC WONDER database to extract mortality data for PC and its comorbidities with diabetes mellitus and metabolic disorders among the U.S. population aged 25 and older from 1999 to 2023. We calculated the Age-Adjusted Mortality Rate (AAMR) and employed Joinpoint regression analysis to assess the average annual percentage change (AAPC), stratifying the data by sex, age, race, region, and urbanization level.

The annual AAMR for PC in the United States increased from 16.41 (95% CI: 16.22 to 16.60) to 17.83 (95% CI: 17.17 to 17.48), with an AAPC of 0.24 (95% CI: 0.19 to 0.30). The AAMR of PC with DM also increased, with an AAPC of 2.21 (95% CI: 1.52 to 2.89; p<0.001), while PC with MDs showed a steeper increase, with an AAPC of 5.45 (95% CI: 4.86 to 6.03; p<0.001). The highest AAMR was observed among males, non-Hispanic blacks, and patients in Southern, Midwestern and nonmetropolitan areas, with a particularly notable increase in non-urban regions.

The mortality rate associated with PC and its metabolic comorbidities continues to rise, indicating the need to strengthen early screening and metabolic management for high-risk populations.