{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:15:36Z","timestamp":1787609736272,"version":"build-2736575974"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Steno Diabetes Center North Jutland"},{"name":"North Denmark Region Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Methods<\/jats:title>\n                  <jats:p>In a Danish nationwide population-based cohort study, we included adults (\u226518 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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 &amp;lt; .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 &amp;lt; .0001) in patients with PPDM. In sensitivity analyses and among individuals with type 2 diabetes, metformin treatment exhibited comparable trends of risk reduction.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvad175","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T21:27:12Z","timestamp":1703280432000},"page":"44-53","source":"Crossref","is-referenced-by-count":16,"title":["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"],"prefix":"10.1093","volume":"190","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-8144","authenticated-orcid":false,"given":"Line","family":"Davidsen","sequence":"first","affiliation":[{"name":"Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital , 9000 Aalborg , Denmark"},{"name":"Department of Clinical Medicine, Aalborg University , 9000 Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6649-8644","authenticated-orcid":false,"given":"Morten H","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, Aalborg University , 9000 Aalborg , Denmark"},{"name":"Data Science, Novo Nordisk A\/S , 2860 S\u00f8borg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4157-1091","authenticated-orcid":false,"given":"Mathias E","family":"Cook","sequence":"additional","affiliation":[{"name":"Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital , 9000 Aalborg , Denmark"},{"name":"Department of Clinical Medicine, Aalborg University , 9000 Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vestergaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aalborg University , 9000 Aalborg , Denmark"},{"name":"Steno Diabetes Centre North Jutland, Aalborg University Hospital , 9000 Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":false,"given":"Filip K","family":"Knop","sequence":"additional","affiliation":[{"name":"Centre for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen , 2900 Hellerup , Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen , 2200 Copenhagen , Denmark"},{"name":"Clinical Research, Steno Diabetes Center Copenhagen , 273 Herlev , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7465-964X","authenticated-orcid":false,"given":"Asbj\u00f8rn M","family":"Drewes","sequence":"additional","affiliation":[{"name":"Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital , 9000 Aalborg , Denmark"},{"name":"Department of Clinical Medicine, Aalborg University , 9000 Aalborg , Denmark"},{"name":"Steno Diabetes Centre North Jutland, Aalborg University Hospital , 9000 Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3916-3168","authenticated-orcid":false,"given":"S\u00f8ren S","family":"Olesen","sequence":"additional","affiliation":[{"name":"Centre for Pancreatic Diseases and Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital , 9000 Aalborg , Denmark"},{"name":"Department of Clinical Medicine, Aalborg University , 9000 Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"issue":"1","key":"2024013107273750200_lvad175-B1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1177\/2050640620966513","article-title":"Time trends in incidence and prevalence of chronic pancreatitis: a 25-year population-based nationwide study","volume":"9","author":"Olesen","year":"2021","journal-title":"United Eur Gastroenterol J"},{"issue":"3","key":"2024013107273750200_lvad175-B2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41575-018-0087-5","article-title":"Global epidemiology and holistic prevention of pancreatitis","volume":"16","author":"Petrov","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"9","key":"2024013107273750200_lvad175-B3","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.2337\/dc21-0333","article-title":"Glucose-lowering therapy in patients with postpancreatitis diabetes mellitus: a nationwide population-based cohort study","volume":"44","author":"Viggers","year":"2021","journal-title":"Diabetes Care"},{"issue":"11","key":"2024013107273750200_lvad175-B4","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.2337\/dc17-0542","article-title":"Incidence, demographics, and clinical characteristics of diabetes of the exocrine pancreas (type 3c): a retrospective cohort study","volume":"40","author":"Woodmansey","year":"2017","journal-title":"Diabetes Care"},{"issue":"6","key":"2024013107273750200_lvad175-B5","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.2337\/dc21-2531","article-title":"Risk of major adverse cardiovascular events, severe hypoglycemia, and all-cause mortality in postpancreatitis diabetes mellitus versus type 2 diabetes: a nationwide population-based cohort study","volume":"45","author":"Olesen","year":"2022","journal-title":"Diabetes Care"},{"issue":"1","key":"2024013107273750200_lvad175-B6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/ueg2.12344","article-title":"Post-pancreatitis diabetes mellitus is common in chronic pancreatitis and is associated with adverse outcomes","volume":"11","author":"Dugic","year":"2023","journal-title":"United Eur Gastroenterol J"},{"issue":"3","key":"2024013107273750200_lvad175-B7","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1159\/000329188","article-title":"Pancreatogenic diabetes: special considerations for management","volume":"11","author":"Cui","year":"2011","journal-title":"Pancreatology"},{"issue":"4","key":"2024013107273750200_lvad175-B8","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.pan.2013.05.002","article-title":"Detection, evaluation and treatment of diabetes mellitus in chronic pancreatitis: recommendations from PancreasFest 2012","volume":"13","author":"Rickels","year":"2013","journal-title":"Pancreatology"},{"issue":"2","key":"2024013107273750200_lvad175-B9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/2050640616684695","article-title":"United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU)","volume":"5","author":"L\u00f6hr","year":"2017","journal-title":"United Eur Gastroenterol J"},{"issue":"9","key":"2024013107273750200_lvad175-B10","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"issue":"10","key":"2024013107273750200_lvad175-B11","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.3390\/ijms19102863","article-title":"Metformin: an old drug with new applications","volume":"19","author":"Zhou","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2024013107273750200_lvad175-B12","doi-asserted-by":"crossref","first-page":"944902","DOI":"10.3389\/fcvm.2022.944902","article-title":"Effect of metformin on adverse outcomes in T2DM patients: systemic review and meta-analysis of observational studies","volume":"9","author":"Xu","year":"2022","journal-title":"Front Cardiovasc Med"},{"issue":"5","key":"2024013107273750200_lvad175-B13","doi-asserted-by":"crossref","first-page":"530","DOI":"10.2337\/diab.35.5.530","article-title":"The diabetes control and complications trial (DCCT): design and methodologic considerations for the feasibility phase","volume":"35","author":"The DCCT Research Group","year":"1986","journal-title":"Diabetes"},{"issue":"12","key":"2024013107273750200_lvad175-B14","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/BF00400195","article-title":"UK prospective diabetes study (UKPDS)","volume":"34","author":"UK Prospective Diabetes Study (UKPDS) Group","year":"1991","journal-title":"Diabetologia"},{"issue":"12","key":"2024013107273750200_lvad175-B15","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s40265-023-01913-5","article-title":"Diabetes of the exocrine pancreas: implications for pharmacological management","volume":"83","author":"Goodarzi","year":"2023","journal-title":"Drugs"},{"issue":"10295","key":"2024013107273750200_lvad175-B16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0140-6736(21)01324-6","article-title":"Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial","volume":"398","author":"Rosenstock","year":"2021","journal-title":"Lancet"},{"issue":"3","key":"2024013107273750200_lvad175-B17","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S2213-8587(13)70084-6","article-title":"Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"1","author":"Roden","year":"2013","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"9","key":"2024013107273750200_lvad175-B18","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.2337\/dc19-0145","article-title":"Antidiabetic medications and mortality risk in individuals with pancreatic cancer-related diabetes and postpancreatitis diabetes: a nationwide cohort study","volume":"42","author":"Cho","year":"2019","journal-title":"Diabetes Care"},{"key":"2024013107273750200_lvad175-B19","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"issue":"8","key":"2024013107273750200_lvad175-B20","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s10654-014-9930-3","article-title":"The Danish Civil Registration System as a tool in epidemiology","volume":"29","author":"Schmidt","year":"2014","journal-title":"Eur J Epidemiol"},{"issue":"3","key":"2024013107273750200_lvad175-B21","first-page":"798","article-title":"Data resource profile: the Danish national prescription registry","volume":"46","author":"Potteg\u00e5rd","year":"2017","journal-title":"Int J Epidemiol"},{"issue":"7_suppl","key":"2024013107273750200_lvad175-B22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/1403494811399958","article-title":"The Danish register of causes of death","volume":"39","author":"Helweg-Larsen","year":"2011","journal-title":"Scand J Public Health"},{"key":"2024013107273750200_lvad175-B23","first-page":"535","article-title":"The Danish cancer registry history, content, quality and use","volume":"44","author":"Storm","year":"1997","journal-title":"Dan Med Bull"},{"key":"2024013107273750200_lvad175-B24","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2147\/CLEP.S245060","article-title":"Existing data sources in clinical epidemiology: laboratory information system databases in Denmark","volume":"12","author":"Arendt","year":"2020","journal-title":"Clin Epidemiol"},{"issue":"7_suppl","key":"2024013107273750200_lvad175-B25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1177\/1403494810394715","article-title":"Danish education registers","volume":"39","author":"Jensen","year":"2011","journal-title":"Scand J Public Health"},{"issue":"7_suppl","key":"2024013107273750200_lvad175-B26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1177\/1403494811408483","article-title":"Danish registers on personal labour market affiliation","volume":"39","author":"Petersson","year":"2011","journal-title":"Scand J Public Health"},{"issue":"6","key":"2024013107273750200_lvad175-B27","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.2337\/dc19-2535","article-title":"Risk of major adverse cardiovascular events, severe hypoglycemia, and all-cause mortality for widely used antihyperglycemic dual and triple therapies for type 2 diabetes management: a cohort study of all Danish users","volume":"43","author":"Jensen","year":"2020","journal-title":"Diabetes Care"},{"issue":"9","key":"2024013107273750200_lvad175-B28","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.2337\/dc20-0207","article-title":"Postpancreatitis diabetes confers higher risk for pancreatic cancer than type 2 diabetes: results from a nationwide cancer registry","volume":"43","author":"Cho","year":"2020","journal-title":"Diabetes Care"},{"issue":"mar12 1","key":"2024013107273750200_lvad175-B29","doi-asserted-by":"crossref","first-page":"b5087","DOI":"10.1136\/bmj.b5087","article-title":"Problem of immortal time bias in cohort studies: example using statins for preventing progression of diabetes","volume":"340","author":"Levesque","year":"2010","journal-title":"BMJ"},{"issue":"5):","key":"2024013107273750200_lvad175-B30","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J Chron Dis"},{"issue":"9131","key":"2024013107273750200_lvad175-B31","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/S0140-6736(98)07037-8","article-title":"Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)","volume":"352","author":"UK Prospective Diabetes Study (UKPDS) Group","year":"1998","journal-title":"Lancet"},{"issue":"3","key":"2024013107273750200_lvad175-B32","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s40256-018-0266-3","article-title":"Cardioprotection by metformin: beneficial effects beyond glucose reduction","volume":"18","author":"Varjabedian","year":"2018","journal-title":"Am J Cardiovasc Drugs"},{"issue":"4","key":"2024013107273750200_lvad175-B33","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00592-007-0004-9","article-title":"Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes","volume":"44","author":"Yilmaz","year":"2007","journal-title":"Acta Diabetol"},{"issue":"3","key":"2024013107273750200_lvad175-B34","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S2468-1253(16)30106-6","article-title":"Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer","volume":"1","author":"Hart","year":"2016","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"1","key":"2024013107273750200_lvad175-B35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/mpa.0b013e31805d01b0","article-title":"Mechanisms and emerging treatments of the metabolic complications of chronic pancreatitis","volume":"35","author":"Andersen","year":"2007","journal-title":"Pancreas"},{"key":"2024013107273750200_lvad175-B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ph15080953","article-title":"Continuous subcutaneous insulin infusion (CSII) combined with oral glucose-lowering drugs in type 2 diabetes\u202f: a systematic review and network meta-analysis of randomized","volume":"15","author":"Li","year":"2022","journal-title":"Controlled Trials"},{"issue":"3","key":"2024013107273750200_lvad175-B37","doi-asserted-by":"crossref","first-page":"101225","DOI":"10.1016\/j.diabet.2021.101225","article-title":"Glucose variability and diabetes complications: risk factor or biomarker? Can we disentangle the \u201cgordian Knot\u201d?","volume":"47","author":"Monnier","year":"2021","journal-title":"Diabetes Metab"},{"issue":"12","key":"2024013107273750200_lvad175-B38","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/1753-0407.13210","article-title":"Clinical and biochemical characteristics of postpancreatitis diabetes mellitus: a cross-sectional study from the Danish nationwide DD2 cohort","volume":"13","author":"Olesen","year":"2021","journal-title":"J Diabetes"},{"issue":"10","key":"2024013107273750200_lvad175-B39","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1097\/MPA.0000000000001930","article-title":"Pancreatogenic diabetes, 2 onset forms and lack of metabolic syndrome components differentiate it from type 2 diabetes","volume":"50","author":"Valdez-Hern\u00e1ndez","year":"2021","journal-title":"Pancreas"},{"issue":"1","key":"2024013107273750200_lvad175-B40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/1403494818773535","article-title":"Positive predictive value of acute and chronic pancreatitis diagnoses in the Danish National Patient Registry: a validation study","volume":"48","author":"Kirkeg\u00e5rd","year":"2020","journal-title":"Scand J Public Health"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejendo\/advance-article-pdf\/doi\/10.1093\/ejendo\/lvad175\/54763449\/lvad175.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/190\/1\/44\/55371534\/lvad175.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejendo\/article-pdf\/190\/1\/44\/55371534\/lvad175.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T07:28:06Z","timestamp":1706686086000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/190\/1\/44\/7491713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,22]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,3]]}},"URL":"https:\/\/doi.org\/10.1093\/ejendo\/lvad175","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1]]},"published":{"date-parts":[[2023,12,22]]}}}