{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:14:54Z","timestamp":1792800894594,"version":"4.5.0"},"reference-count":10,"publisher":"Bioscientifica","issue":"3","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>We describe a case of concurrent metformin-associated lactic acidosis (MALA) and euglycemic diabetic ketoacidosis (EDKA) in a 64-year-old woman with type 2 diabetes mellitus (T2DM) treated with metformin and tirzepatide who presented with shock, encephalopathy, and severe high anion gap metabolic acidosis after two weeks of markedly reduced oral intake following tirzepatide dose escalation. While incretin-based therapies, including dual glucose-dependent insulinotropic polypeptide\/glucagon-like peptide-1 receptor agonists (GIP\/GLP-1 RAs) such as tirzepatide, are highly effective for glycemic control and weight management, gastrointestinal (GI) adverse effects may lead to prolonged caloric restriction and starvation physiology. In this patient, starvation ketosis progressed to EDKA, while concurrent dehydration and acute kidney injury (AKI) impaired metformin clearance, resulting in MALA with markedly elevated lactate. The patient required endotracheal intubation, vasopressor support, and continuous renal replacement therapy (CRRT), with rapid clinical and metabolic improvement following discontinuation of metformin and tirzepatide. This case highlights the potential for severe overlapping metabolic complications involving starvation-related ketoacidosis, dehydration, AKI, and impaired metformin clearance when incretin-based therapies are continued during prolonged poor oral intake.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Learning points<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1530\/edm-26-0025","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:52:55Z","timestamp":1790358775000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":1,"title":["Concurrent metformin-associated lactic acidosis and euglycemic diabetic ketoacidosis from tirzepatide starvation ketosis"],"prefix":"10.1530","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7681-6176","authenticated-orcid":true,"given":"Frank","family":"Epitropoulos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Brijawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khizar","family":"Ghuman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Will","family":"Van Beusekom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inderpal","family":"Thethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2026092513525139100_bib1","doi-asserted-by":"crossref","first-page":"R211","DOI":"10.1530\/EJE-19-0566","article-title":"Management of endocrine disease: are all GLP-1 agonists equal in the treatment of type 2 diabetes?","volume":"181","author":"Nauck","year":"2019","journal-title":"Eur J Endocrinol"},{"key":"2026092513525139100_bib2","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.cmet.2018.03.001","article-title":"Mechanisms of action and therapeutic application of glucagon-like peptide-1","volume":"27","author":"Drucker","year":"2018","journal-title":"Cell Metab"},{"key":"2026092513525139100_bib3","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1056\/NEJM197003192821209","article-title":"Starvation in man","volume":"282","author":"Cahill","year":"1970","journal-title":"N Engl J Med"},{"key":"2026092513525139100_bib4","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/pds.3689","article-title":"Mortality rate in so-called \u201cmetformin-associated lactic acidosis\u201d: a review of the data since the 1960s","volume":"23","author":"Kajbaf","year":"2014","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2026092513525139100_bib5","doi-asserted-by":"crossref","DOI":"10.1186\/cc11332","article-title":"Metformin overdose, but not lactic acidosis per se, inhibits oxygen consumption in pigs","volume":"16","author":"Protti","year":"2012","journal-title":"Crit Care"},{"key":"2026092513525139100_bib6","article-title":"Euglycemic ketoacidosis from semaglutide in a patient without diabetes","volume":"2","author":"Sood","year":"2024","journal-title":"JCEM Case Rep"},{"key":"2026092513525139100_bib7","article-title":"Tirzepatide-induced ketoacidosis in non-diabetic patients","volume":"11","author":"Iqbal","year":"2024","journal-title":"Eur J Case Rep Intern Med"},{"key":"2026092513525139100_bib8","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000034027","article-title":"Euglycemic diabetic ketoacidosis after the initiation of dulaglutide in patient with type 2 diabetes","volume":"102","author":"Alduraibi","year":"2023","journal-title":"Medicine"},{"key":"2026092513525139100_bib9","article-title":"Unanticipated adverse events with tirzepatide: three cases underscoring the importance of postmarketing monitoring","volume":"3","author":"Colorado","year":"2025","journal-title":"JCEM Case Rep"},{"key":"2026092513525139100_bib10","article-title":"Tirzepatide. [Updated 2024 Feb 20]","volume-title":"StatPearls [Internet]","author":"Farzam","year":"2025"}],"container-title":["Endocrinology, Diabetes &amp; Metabolism Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.bioscientifica.com\/edm\/article-pdf\/doi\/10.1530\/EDM-26-0025\/525764\/edm-26-0025.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/edm\/article-pdf\/doi\/10.1530\/EDM-26-0025\/525764\/edm-26-0025.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:52:57Z","timestamp":1790358777000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/edm\/article\/2026\/3\/EDM260025\/78273\/Concurrent-metformin-associated-lactic-acidosis"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,1]]},"references-count":10,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1530\/edm-26-0025","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,1]]},"article-number":"EDM260025"}}