Metformin treatment is associated with reduced risk of hypoglycaemia, major adverse cardiovascular events, and all-cause mortality in patients with post-pancreatitis diabetes mellitus: a nationwide cohort study

• Published in: European journal of endocrinology Vol. 190; no. 1; pp. 44 - 53
• Main Authors: Davidsen, Line, Jensen, Morten H, Cook, Mathias E, Vestergaard, Peter, Knop, Filip K, Drewes, Asbjørn M, Olesen, Søren S
• Format: Journal Article
• Language: English
• Published: England 03.01.2024
• Subjects: Adult; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - epidemiology; Cohort Studies; Diabetes Mellitus, Type 2 - chemically induced; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Glucose; Humans; Hypoglycemia - chemically induced; Hypoglycemic Agents - adverse effects; Metformin - adverse effects; Pancreatitis - complications; Pancreatitis - drug therapy; treatment; metformin; diabetes mellitus; pancreatitis
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1093/ejendo/lvad175

Post-pancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis and is associated with an increased risk of adverse outcomes. Metformin is recommended for the treatment of PPDM, but evidence of its risk-benefit profile is limited. In a pharmaco-epidemiologic study, we investigated the association between metformin treatment and adverse outcomes in patients with PPDM. In a Danish nationwide population-based cohort study, we included adults (≥18 years) with incident PPDM or type 2 diabetes between 2009 and 2018. Post-pancreatitis diabetes mellitus was categorised into acute and chronic subtypes (PPDM-A and PPDM-C). Associations between metformin treatment and severe hypoglycaemia, major adverse cardiovascular events (MACE), and all-cause mortality were examined across the diabetes subgroups using Cox regression analysis. Treatments with metformin, insulin, and other glucose-lowering therapies were handled as time-varying exposures. We included 222 337 individuals with new-onset type 2 diabetes and 3781 with PPDM, of whom 2305 (61%) were classified as PPDM-A and 1476 (39%) as PPDM-C. Treatment with metformin was associated with a lower risk of severe hypoglycaemia (adjusted hazard ratio [HR] 0.41, 95% CI 0.27-0.62, P < .0001), MACE (HR 0.74, 95% CI 0.60-0.92, P = .0071), and all-cause mortality (HR 0.56, 95% CI 0.49-0.64, P < .0001) in patients with PPDM. In sensitivity analyses and among individuals with type 2 diabetes, metformin treatment exhibited comparable trends of risk reduction. Metformin is associated with a lower risk of adverse outcomes, including all-cause mortality in patients with PPDM, supporting the use of metformin as a glucose-lowering therapy for these patients.