{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:22:34Z","timestamp":1792113754165,"version":"4.4.0"},"reference-count":29,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T00:00:00Z","timestamp":1717286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>People with clinically diagnosed type 2 diabetes (T2D) but positive antiglutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>This work aimed to assess glycated hemoglobin A1c (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive vs GADA-negative participants with a clinical T2D diagnosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status, were conducted on 3791 individuals. Intervention included tirzepatide (5, 10, 15\u2005mg). Main outcome measure included change from baseline in HbA1c at weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4) by GADA status.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In participants with confirmed GADA status, 3671 (96.8%) were GADA negative and 120 (3.2%) were GADA positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive vs GADA-negative participants (mean [SD] BMI 32.2 [6.1] vs 33.6 [6.3]). At week 40\/42, both groups achieved robust reductions in HbA1c (\u22122.11% vs \u22122.32%) and BW (\u20139.2\u2005kg vs \u22129.6\u2005kg) (P &amp;lt; .001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; P = .024) and BW reductions did not differ between groups (0.38\u2005kg [\u22120.99, 1.75]; P = .588).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae372","type":"journal-article","created":{"date-parts":[[2024,6,2]],"date-time":"2024-06-02T22:45:12Z","timestamp":1717368312000},"page":"e962-e969","source":"Crossref","is-referenced-by-count":13,"title":["Improved HbA1c and Body Weight in GADA-Positive Individuals Treated With Tirzepatide: A Post Hoc Analysis of SURPASS"],"prefix":"10.1210","volume":"110","author":[{"given":"Anne L","family":"Peters","sequence":"first","affiliation":[{"name":"University of Southern California Clinical Diabetes Program, Keck School of Medicine of the University of Southern California, Los Angeles , Los Angeles, CA 90033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Buzzetti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome , Rome 00160 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-0207","authenticated-orcid":false,"given":"Clare J","family":"Lee","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN 46285 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imre","family":"Pavo","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN 46285 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minzhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Tigermed-BCM Inc , Somerset, NJ 08873 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrisanthi A","family":"Karanikas","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN 46285 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim S","family":"Paik","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company , Indianapolis, IN 46285 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"issue":"11","key":"2025031717082697000_dgae372-B1","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.2337\/dc21-0770","article-title":"Adult-onset type 1 diabetes: current understanding and challenges","volume":"44","author":"Leslie","year":"2021","journal-title":"Diabetes Care"},{"issue":"11","key":"2025031717082697000_dgae372-B2","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1007\/s00125-005-1960-7","article-title":"Latent autoimmune diabetes in adults (LADA) should be less latent","volume":"48","author":"Fourlanos","year":"2005","journal-title":"Diabetologia"},{"issue":"1","key":"2025031717082697000_dgae372-B3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41572-022-00390-6","article-title":"Adult-onset autoimmune diabetes","volume":"8","author":"Buzzetti","year":"2022","journal-title":"Nat Rev Dis Primers"},{"issue":"10","key":"2025031717082697000_dgae372-B4","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.2337\/dbi20-0017","article-title":"Management of latent autoimmune diabetes in adults: a consensus statement from an international expert panel","volume":"69","author":"Buzzetti","year":"2020","journal-title":"Diabetes"},{"issue":"3","key":"2025031717082697000_dgae372-B5","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/dmrr.2717","article-title":"Saxagliptin improves glycaemic control and C-peptide secretion in latent autoimmune diabetes in adults (LADA)","volume":"32","author":"Buzzetti","year":"2016","journal-title":"Diabetes Metab Res Rev"},{"issue":"6","key":"2025031717082697000_dgae372-B6","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1111\/dom.13237","article-title":"Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults (LADA): a post-hoc analysis of the AWARD-2, -4 and -5 trials","volume":"20","author":"Pozzilli","year":"2018","journal-title":"Diabetes Obes Metab"},{"issue":"10295","key":"2025031717082697000_dgae372-B7","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":"6","key":"2025031717082697000_dgae372-B8","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes","volume":"385","author":"Fr\u00edas","year":"2021","journal-title":"N Engl J Med"},{"issue":"10300","key":"2025031717082697000_dgae372-B9","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0140-6736(21)01443-4","article-title":"Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial","volume":"398","author":"Ludvik","year":"2021","journal-title":"Lancet"},{"issue":"10313","key":"2025031717082697000_dgae372-B10","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/S0140-6736(21)02188-7","article-title":"Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial","volume":"398","author":"Prato","year":"2021","journal-title":"Lancet"},{"issue":"6","key":"2025031717082697000_dgae372-B11","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1001\/jama.2022.0078","article-title":"Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial","volume":"327","author":"Dahl","year":"2022","journal-title":"JAMA"},{"issue":"4","key":"2025031717082697000_dgae372-B12","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4239\/wjd.v5.i4.505","article-title":"Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus","volume":"5","author":"Pipi","year":"2014","journal-title":"World J Diabetes"},{"issue":"1","key":"2025031717082697000_dgae372-B13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2337\/dc14-1770","article-title":"Latent autoimmune diabetes in adults with low-titer GAD antibodies: similar disease progression with type 2 diabetes: a nationwide, multicenter prospective study (LADA China study 3)","volume":"38","author":"Liu","year":"2015","journal-title":"Diabetes Care"},{"issue":"3","key":"2025031717082697000_dgae372-B14","doi-asserted-by":"crossref","first-page":"476","DOI":"10.2337\/dc14-1952","article-title":"Prevalence of detectable C-peptide according to age at diagnosis and duration of type 1 diabetes","volume":"38","author":"Davis","year":"2015","journal-title":"Diabetes Care"},{"issue":"1","key":"2025031717082697000_dgae372-B15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6823-15-1","article-title":"Insulin secretion in patients with latent autoimmune diabetes (LADA): half way between type 1 and type 2 diabetes: action LADA 9","volume":"15","author":"Hernandez","year":"2015","journal-title":"BMC Endocr Disord"},{"issue":"6","key":"2025031717082697000_dgae372-B16","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2337\/diacare.27.6.1487","article-title":"Use and abuse of HOMA modeling","volume":"27","author":"Wallace","year":"2004","journal-title":"Diabetes Care"},{"key":"2025031717082697000_dgae372-B17","unstructured":"Peters AL, Buzzetti R, Lee CJ, et al Supplemental appendix: improved HbA1c and body weight in GADA-positive individuals treated with tirzepatide: a post hoc analysis of SURPASS. Zenodo. https:\/\/zenodo.org\/deposit\/11454669"},{"issue":"11","key":"2025031717082697000_dgae372-B18","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2337\/dci22-0034","article-title":"Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"45","author":"Davies","year":"2022","journal-title":"Diabetes Care"},{"issue":"10322","key":"2025031717082697000_dgae372-B19","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S0140-6736(21)01919-X","article-title":"Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation","volume":"399","author":"Lingvay","year":"2022","journal-title":"Lancet"},{"issue":"Suppl 1","key":"2025031717082697000_dgae372-B20","doi-asserted-by":"crossref","first-page":"S128","DOI":"10.2337\/dc23-S008","article-title":"8. Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes-2023","volume":"46","author":"ElSayed","year":"2023","journal-title":"Diabetes Care"},{"issue":"2","key":"2025031717082697000_dgae372-B21","doi-asserted-by":"crossref","first-page":"250","DOI":"10.2337\/dc15-0258","article-title":"Markers of \u03b2-cell failure predict poor glycemic response to GLP-1 receptor agonist therapy in type 2 diabetes","volume":"39","author":"Jones","year":"2016","journal-title":"Diabetes Care"},{"issue":"10","key":"2025031717082697000_dgae372-B22","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1056\/NEJMc2302677","article-title":"Semaglutide in early type 1 diabetes","volume":"389","author":"Dandona","year":"2023","journal-title":"N Engl J Med"},{"issue":"6","key":"2025031717082697000_dgae372-B23","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/S2213-8587(22)00085-7","article-title":"Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial","volume":"10","author":"Heise","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"2","key":"2025031717082697000_dgae372-B24","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1210\/clinem\/dgaa863","article-title":"Dual GIP and GLP-1 receptor agonist tirzepatide improves beta-cell function and insulin sensitivity in type 2 diabetes","volume":"106","author":"Thomas","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2025031717082697000_dgae372-B25","doi-asserted-by":"crossref","first-page":"bvad056","DOI":"10.1210\/jendso\/bvad056","article-title":"Tirzepatide as monotherapy improved markers of beta-cell function and insulin sensitivity in type 2 diabetes (SURPASS-1)","volume":"7","author":"Lee","year":"2023","journal-title":"J Endocr Soc"},{"key":"2025031717082697000_dgae372-B26","doi-asserted-by":"crossref","first-page":"170213","DOI":"10.1016\/j.peptides.2019.170213","article-title":"The role of GIP in \u03b1-cells and glucagon secretion","volume":"125","author":"El","year":"2020","journal-title":"Peptides"},{"issue":"12","key":"2025031717082697000_dgae372-B27","doi-asserted-by":"crossref","first-page":"e146353","DOI":"10.1172\/JCI146353","article-title":"GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice","volume":"131","author":"Samms","year":"2021","journal-title":"J Clin Invest"},{"issue":"6","key":"2025031717082697000_dgae372-B28","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/dmrr.2411","article-title":"Action LADA 8. Latent autoimmune diabetes in adults is perched between type 1 and type 2: evidence from adults in one region of Spain","volume":"29","author":"Mollo","year":"2013","journal-title":"Diabetes Metab Res Rev"},{"issue":"4","key":"2025031717082697000_dgae372-B29","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2337\/dc12-0931","article-title":"Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: action LADA 7","volume":"36","author":"Hawa","year":"2013","journal-title":"Diabetes Care"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgae372\/58181620\/dgae372.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/4\/e962\/58181620\/dgae372.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/4\/e962\/58181620\/dgae372.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T17:08:45Z","timestamp":1742231325000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/4\/e962\/7686558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,3]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,6,3]]},"published-print":{"date-parts":[[2025,3,17]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgae372","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2024,6,3]]}}}