Background: A causal relationship between diabetes mellitus (DM) and pancreatic cancer (PC) is well established. However, in patients with advanced PC (APC) who receive palliative chemotherapy, the impact of DM on prognosis is unclear. Methods: Between 2003 and 2010, we enrolled consecutive patients with APC, all recipients of palliative chemotherapy, with the provision that DM disease status could be properly defined. Enrollees were stratified by diagnosis, in accordance with 2010 DM criteria (AHA/ADA). DM at least 2 years' duration prior to diagnosis of APC qualified as remote-onset DM (vs recent-onset). Clinical characteristics and outcomes were then analyzed. Results: Of the 349 enrollees with APC, 183 (52.4%) had DM. In patients with DM, 160 had DM at the time APC was diagnosed (remote onset, 87; recent onset, 73); and the remaining 23 developed DM during the course of APC treatment. Ultimately, 73.2% (134/183) of DM patients received antidiabetic medication (metformin (56), sulfonylurea (62), insulin (43)). By multivariate analysis, cancer extent (HR, 1.792; p < 0.001) and weight loss during chemotherapy (HR, 1.270; p = 0.08) were associated with diminished overall survival (OS), whereas a diagnosis of DM (HR, 0.788; p = 0.05) conferred a positive effect on OS ( OS 8.4 months in DM patients vs 7.5 months in non-DM patients, p = 0.04). Among DM patients, recent-onset DM trended toward prolonged OS, compared with remote-onset/subsequent DM (9.8 months vs. 7.9 months, respectively; HR, 0.789; p = 0.142). Neither antidiabetic medication in general nor sulfonylurea or insulin specifically affected OS. However, recipients of metformin survived longer than non-recipients (HR, 0.693; 95% CI, 0.492-0.977; p = 0.036). Relative to the APC cohort overall including non-DM patients, metformin conferred better survival as well (11.0 months vs. 7.8 months, HR 0.712, p = 0.067), given similar baseline clinical characteristics. Conclusions: In patients with APC receiving palliative chemotherapy, recent-onset DM (within 2 years of APC diagnosis) and metformin treatment are positive prognosticators, associated with prolonged OS.