{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:30:48Z","timestamp":1779208248345,"version":"3.51.4"},"reference-count":29,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100014786","name":"Northern Border University","doi-asserted-by":"publisher","award":["NBU-FFR2025-396-03"],"award-info":[{"award-number":["NBU-FFR2025-396-03"]}],"id":[{"id":"10.13039\/501100014786","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Endocrinology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n Background:<\/jats:title>\n Metformin is the first-line pharmacological treatment for type 2 diabetes mellitus. Metformin-associated lactic acidosis is uncommon; however, subclinical increases in lactate levels can yield considerable clinical consequences, warranting regular surveillance in high-risk patients. Limited data exist on the patterns of metformin dosing and specific patient factors that may elevate lactate levels, indicating a critical need for further investigation.<\/jats:p>\n <\/jats:sec>\n \n Objectives:<\/jats:title>\n This study aimed to determine the patterns of metformin dosing and identify patient-specific factors associated with higher lactate levels.<\/jats:p>\n <\/jats:sec>\n \n Design:<\/jats:title>\n A retrospective, cross-sectional study.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Patients who attended the endocrinology and internal medicine clinic between January 2021 and December 2022 were included. Patients\u2019 data, including demographics, comorbidities, prescribed medications, and laboratory tests, were collected from electronic health records. Patients were categorized based on age (middle-aged <65\u2009years and older \u2a7e65\u2009years) and metformin dosage (low, medium, and high). Univariable analyses were performed to assess the difference between the comparison groups. Multivariable linear regression analysis was performed to identify factors associated with elevated lactate levels.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Among 3304 diabetic patients, 2329 were metformin users. Metformin users exhibited significantly higher lactate levels (1.9 vs 1.0\u2009mmol\/L,\n p<\/jats:italic>\n \u2009<\u20090.001) compared to nonusers. Older patients had a higher prevalence of comorbidities such as heart failure (74 vs 55,\n p<\/jats:italic>\n \u2009<\u20090.001) and renal disease (3 vs 1,\n p<\/jats:italic>\n \u2009=\u20090.01) but received lower metformin doses compared to middle-aged patients. Increasing metformin dosage (\u03b2\u2009=\u20090.66,\n p<\/jats:italic>\n \u2009<\u20090.001), renal impairment (\u03b2\u2009=\u20090.2,\n p<\/jats:italic>\n \u2009<\u20090.001) and co-prescription of diuretics (\u03b2\u2009=\u20090.2,\n p<\/jats:italic>\n \u2009<\u20090.001) and nonsteroidal anti-inflammatory drugs (\u03b2\u2009=\u20090.1,\n p<\/jats:italic>\n \u2009=\u20090.001) were associated with elevated lactate level, whereas co-prescription of renin-angiotensin-aldosterone inhibitors showed negative association with high lactate level (\u03b2\u2009=\u2009\u22120.25,\n p<\/jats:italic>\n \u2009<\u20090.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Metformin users demonstrated higher lactate levels, with increasing doses and renal impairment being key risk factors. This study calls attention to the importance of routine lactate monitoring, particularly in older adults and patients with renal dysfunction or polypharmacy.<\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/20420188261434647","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T08:48:16Z","timestamp":1775206096000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Factors potentiating risk of higher lactate level associated with metformin therapy: a cross-sectional study in an ambulatory care setting"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4284-0265","authenticated-orcid":false,"given":"Aymen","family":"Alqurain","sequence":"first","affiliation":[{"name":"Department of Clinical Practice, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amani S.","family":"Alrossies","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abrar A.","family":"Almuayli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Maternity and Children Hospital, Al-Ahsa Health Cluster, Al-Ahsa, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayat M.","family":"Alherz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Almoosa Health Group, Al-Ahsa, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munther S.","family":"Alkhamees","sequence":"additional","affiliation":[{"name":"North Sector, Primary Care Medicine, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hawra","family":"Al-Ghafli","sequence":"additional","affiliation":[{"name":"Bioengineering Department, King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia"},{"name":"Interdisciplinary Research Center for Biosystems and Machines, King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nida","family":"Alsaffar","sequence":"additional","affiliation":[{"name":"Independent Researcher, Dammam, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Zawiah","sequence":"additional","affiliation":[{"name":"Department of Clinical Practice, Faculty of Pharmacy, Northern Border University, Rafha, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4336-x"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11808"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1396031"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-017-0564-6"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/emermed-2014-204305"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.10.014"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0125-4"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-019-00742-0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00059814"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.2337\/diaclin.29.3.97"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002967.pub3"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1357171"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13206187"},{"key":"e_1_3_4_15_2","volume-title":"International statistical classification of disease and related health problems 10th revision (ICD-10)\u2014WHO Version for 2016","author":"World Health Organisation","year":"2016","unstructured":"World Health Organisation. International statistical classification of disease and related health problems 10th revision (ICD-10)\u2014WHO Version for 2016. Geneva: World Health Organization, 2016."},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-021122"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000180580"},{"key":"e_1_3_4_18_2","unstructured":"World Health Organization. Anatomical therapeutic chemical (ATC) classification index with defined daily doses (DDDs). In: Methodology CCfDS (ed.) Oslo: World Health Organisation 2000."},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61602-X"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-2361"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.07.011"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbs.2022.108809"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.665250"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3949\/ccjm.86a.18024"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.7.1791"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000450862"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.2337\/dci18-0033"},{"key":"e_1_3_4_28_2","article-title":"Introduction and methodology: standards of care in diabetes\u20142023","volume":"46","author":"ElSayed NA","year":"2023","unstructured":"ElSayed NA, Aleppo G, Aroda VR, et al. Introduction and methodology: standards of care in diabetes\u20142023. Diabetes Care 2023; 46(Suppl. 1): S1\u2013S4.","journal-title":"Diabetes Care"},{"key":"e_1_3_4_29_2","article-title":"2. Classification and diagnosis of diabetes: standards of care in diabetes\u20142023","volume":"46","author":"ElSayed NA","year":"2023","unstructured":"ElSayed NA, Aleppo G, Aroda VR, et al. 2. Classification and diagnosis of diabetes: standards of care in diabetes\u20142023. Diabetes Care 2023; 46(Suppl. 1): S19\u2013S40.","journal-title":"Diabetes Care"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2013.06.012"}],"container-title":["Therapeutic Advances in Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20420188261434647","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20420188261434647","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20420188261434647","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:37:17Z","timestamp":1777592237000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20420188261434647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":29,"alternative-id":["10.1177\/20420188261434647"],"URL":"https:\/\/doi.org\/10.1177\/20420188261434647","relation":{},"ISSN":["2042-0188","2042-0196"],"issn-type":[{"value":"2042-0188","type":"print"},{"value":"2042-0196","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"article-number":"20420188261434647"}}