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. 2024 Jan 3;190(1):44-53.
doi: 10.1093/ejendo/lvad175.

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

Line Davidsen  1   2 , Morten H Jensen  3   4 , Mathias E Cook  1   2 , Peter Vestergaard  2   5 , Filip K Knop  6   7   8 , Asbjørn M Drewes  1   2   5 , Søren S Olesen  1   2
Affiliations

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

Line Davidsen et al. Eur J Endocrinol. .

Abstract

Objective: 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.

Design and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: diabetes mellitus; metformin; pancreatitis; treatment.

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Conflict of interest statement

Conflict of interest: M.H.J. is an employee at Novo Nordisk and holds shares in Novo Nordisk. Co-author F.K.K. is on the editorial board of EJE. He was not involved in the review or editorial process for this paper, on which he is listed as author. No other potential conflicts of interest relevant to this article were reported.

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