Distinct prognostic impact of diabetes subtypes, metformin use, and glycemic control in pancreatic cancer: a systematic review and meta-analysis of cohort studies
Abstract
Background: The prognostic significance of glycemic status in pancreatic ductal adenocarcinoma (PDAC) remains controversial, largely due to heterogeneity in the exposure definitions (new-onset vs. long-standing diabetes, metformin use, and single fasting glucose measurement). This meta-analysis aimed to clarify the association of four distinct glycemic exposures with overall survival (OS) in patients with PDAC.
Methods: We systematically searched Web of Science, PubMed, and EMBASE from 1 January 2010 to 1 June 2026. Cohort studies reporting hazard ratios (HRs) for OS were included and categorized into four subgroups: 1) new-onset diabetes (NOD) vs. non-diabetes; 2) long-standing diabetes (LSD) vs. non-diabetes; 3) metformin use vs. non-use; and 4) hyperglycemia (elevated preoperative fasting glucose or poor glycemic control) vs. normoglycemia. Random-effects meta-analyses were performed. Heterogeneity was assessed using I 2, and publication bias was evaluated via funnel plots and the trim-and-fill method.
Results: A total of 21 studies (six for NOD, four for LSD, six for metformin, and eight for hyperglycemia) were included. NOD was significantly associated with worse OS (pooled HR = 1.33, 95%CI = 1.13-1.57, I 2 = 72.5%). LSD showed no significant association (HR = 1.21, 95%CI = 0.98-1.49, I 2 = 70.1%). Metformin use was associated with a 33% reduction in mortality (HR = 0.67, 95%CI = 0.53-0.84, I 2 = 70.5%). Preoperative hyperglycemia or poor glycemic control consistently…
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