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Introduction Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and Type 2 Diabetes mellitus (T2DM) is both a risk factor for and a consequence of PDAC. However, long-term national trends in combined PDAC-T2DM-related mortality and future projections are not well understood.Methods This population-based retrospective cohort study utilised the CDC WONDER database to identify deaths among US residents aged ≥25 years (2000–2024) with ICD-10 codes for pancreatic adenocarcinoma (C25.0–C25.9) and T2DM (E11.0–E11.9). Age-adjusted mortality rates (AAMRs) were calculated per 1,000,000 population. Joinpoint regression estimated annual percentage changes (APCs) and ARIMA modeling forecasted mortality through 2034.Results From 2000–2024, there were 28,206 PDAC-T2DM-related deaths (12,820 females; 15,386 males). Overall AAMR ( figure 1) increased from 2.39 (95% CI 2.16–2.61) in 2000 to 9.17 (8.81–9.52) in 2024 (APC 2000–2009: 5.47%; 2012–2024: 8.13%). Male AAMRs rose from 2.67 to 11.15, with APC 8.15% (2014–2024); female AAMRs rose from 2.16 to 7.50, APC 8.47% (2014–2024). Older adults (≥65 years) had substantially higher AAMRs, increasing from 10.06 to 38.20, with APC 7.84% (2012–2024); among ages 45–64, AAMR rose from 1.23 to 4.81, with APC 12.34% (2014–2021).By race/ethnicity, AAMRs in 2024 were 9.97 (8.78–11.17) for non-Hispanic Black, 8.79 (8.39–9.20) for non-Hispanic White, and 11.7 (10.4–13.0) for Hispanic/Latino individuals, with significant recent increases in all groups (e.g., APC 7.56% in Black populations 2015–2024; APC 6.32% in Hispanic/Latino 2000–2024) (figure 2). AAMRs rose in all census regions, highest in the West (13.35 in 2024; APC 6.95% over 2000–2024), with pronounced clustering in western and mid-northern states (e.g., California, Nebraska, Minnesota). Non-metropolitan areas had higher AAMRs than metropolitan areas (9.14 vs 6.27 in 2020), with significant increases in both settings. Deaths most commonly occurred at home (15,320; 54%), with rising hospice deaths over time.ARIMA models projected that the overall AAMR would reach 14.63 (95% CI 9.65–19.60) by 2034. Forecasts indicated marked elevations in older adults (61.48; 40.53–82.44), in the West (16.59; 14.05–19.14), and in non-metropolitan areas (12.10; 8.11–16.09 by 2030).Conclusions Mortality from concurrent pancreatic adenocarcinoma and T2DM has risen, with marked disparities by sex, race, age, and region, and the projected increase underscores the need for targeted prevention and early detection in high-risk diabetic populations.Abstract P154 Figure 1Overall and sex-stratified Pancreatic adenocarcinoma and Type 2 Diabetes mellitus-related age-adjusted mortality rates per 1,000,000 in the United States, 2000 to 2024* Indicates that the annual percentage change (APC) is significantly different from zero at α = 0.05.