{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:08:23Z","timestamp":1792080503860,"version":"4.4.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T00:00:00Z","timestamp":1742601600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T00:00:00Z","timestamp":1742601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>Weight loss can improve glycaemic management in individuals with type 2 diabetes, but its long-term effects on remission, cardiovascular risk factors and complications remain unclear. We investigated clinical outcomes following non-interventional \u226510% body weight loss in people with newly diagnosed type 2 diabetes in a routine care setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively analysed two cohorts of people with newly diagnosed type 2 diabetes. After exclusions, cohort 1 included 1934 individuals followed for up to 25 years; cohort 2 comprised 13,277 individuals followed for up to 10 years. Participants were categorised into two groups based on whether or not they lost at least 10% body weight. In a sensitivity analysis, a group of participants with intermediate weight loss (5% to &lt;10%) was also considered. Outcomes included HbA\n                      <jats:sub>1c<\/jats:sub>\n                      , diabetes remission, cardiovascular parameters and chronic complications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Participants (58% male) had a mean age of 62 years and a mean diabetes duration of &lt;2 years at inclusion; mean baseline HbA\n                      <jats:sub>1c<\/jats:sub>\n                      was 57\u201364 mmol\/mol (7.4\u20138.0%) and mean BMI was ~30 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      . Weight loss \u226510% was obtained in 15.9% (\n                      <jats:italic>n<\/jats:italic>\n                      =308) of participants in cohort 1 and in 8.8% (\n                      <jats:italic>n<\/jats:italic>\n                      =1167) in cohort 2. In cohort 1, weight loss \u226510% was associated with a sustained reduction in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      (mean difference 2.1 mmol\/mol; 0.19%) and a higher remission rate than in the &lt;10% weight loss group (20.2% vs 5.5%; HR 4.2). These findings were confirmed in cohort 2, with remission rates of 13.2% and 4.1% (HR 2.6) in the \u226510% and &lt;10% weight loss groups, respectively. Weight loss \u226510% improved systolic BP and HDL-cholesterol and triglyceride levels. Participants with weight loss of 5% to &lt;10% (28.2% in cohort 1 and 17.4% in cohort 2) had marginal improvements in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      , lipids and remission rates compared with participants with weight loss &lt;5%, and such results were inferior to those achieved with weight loss \u226510%. In cohort 1, compared with weight loss &lt;5% (reference), the HR for remission was 5.2 with weight loss \u226510% vs 1.7 with weight loss 5% to &lt;10%. Weight loss \u226510% was not associated with a reduced incidence of complications. On the other hand, remission was independently associated with a significantly lower rate of new-onset microangiopathy (adjusted HR 0.84; 95% CI 0.73, 0.97;\n                      <jats:italic>p<\/jats:italic>\n                      =0.019).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Early weight loss of \u226510% in type 2 diabetes was associated with sustained glycaemic improvements, increasing by three to four times the rates of diabetes remission. Remission, in turn, more than weight loss was associated with a reduced risk of complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06402-w","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T06:58:10Z","timestamp":1742713090000},"page":"1115-1125","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Early weight loss, diabetes remission and long-term trajectory after diagnosis of type 2 diabetes: a retrospective study"],"prefix":"10.1007","volume":"68","author":[{"given":"Mario Luca","family":"Morieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Rigato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Frison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Sartore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Avogaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6510-2097","authenticated-orcid":false,"given":"Gian Paolo","family":"Fadini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,22]]},"reference":[{"issue":"10322","key":"6402_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/S0140-6736(21)01919-X","volume":"399","author":"I Lingvay","year":"2022","unstructured":"Lingvay I, Sumithran P, Cohen RV, le Roux CW (2022) Obesity management as a primary treatment goal for type 2 diabetes: time to reframe the conversation. Lancet 399(10322):394\u2013405. https:\/\/doi.org\/10.1016\/S0140-6736(21)01919-X","journal-title":"Lancet"},{"issue":"9","key":"6402_CR2","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/S2213-8587(19)30076-2","volume":"7","author":"R Taylor","year":"2019","unstructured":"Taylor R, Al-Mrabeh A, Sattar N (2019) Understanding the mechanisms of reversal of type 2 diabetes. Lancet Diabetes Endocrinol 7(9):726\u2013736. https:\/\/doi.org\/10.1016\/S2213-8587(19)30076-2","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"2","key":"6402_CR3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1056\/NEJMoa1212914","volume":"369","author":"RR Wing","year":"2013","unstructured":"Wing RR, Bolin P, Brancati FL et al (2013) Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 369(2):145\u2013154. https:\/\/doi.org\/10.1056\/NEJMoa1212914","journal-title":"N Engl J Med"},{"issue":"23","key":"6402_CR4","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1001\/jama.2012.67929","volume":"308","author":"EW Gregg","year":"2012","unstructured":"Gregg EW, Chen H, Wagenknecht LE et al (2012) Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA 308(23):2489\u20132496. https:\/\/doi.org\/10.1001\/jama.2012.67929","journal-title":"JAMA"},{"issue":"5","key":"6402_CR5","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1002\/osp4.504","volume":"7","author":"E Jacob","year":"2021","unstructured":"Jacob E, Avery A (2021) Energy-restricted interventions are effective for the remission of newly diagnosed type 2 diabetes: a systematic review of the evidence base. Obes Sci Pract 7(5):606\u2013618. https:\/\/doi.org\/10.1002\/osp4.504","journal-title":"Obes Sci Pract"},{"issue":"10","key":"6402_CR6","doi-asserted-by":"publisher","first-page":"2438","DOI":"10.2337\/dci21-0034","volume":"44","author":"MC Riddle","year":"2021","unstructured":"Riddle MC, Cefalu WT, Evans PH et al (2021) Consensus report: definition and interpretation of remission in type 2 diabetes. Diabetes Care 44(10):2438\u20132444. https:\/\/doi.org\/10.2337\/dci21-0034","journal-title":"Diabetes Care"},{"issue":"6","key":"6402_CR7","doi-asserted-by":"publisher","first-page":"e13733","DOI":"10.1111\/obr.13733","volume":"25","author":"AN Aksoy","year":"2024","unstructured":"Aksoy AN, Abayomi J, Relph N, Butler T (2024) Physiological and psychological determinants of long-term diet-induced type 2 diabetes (T2DM) remission: a narrative review. Obes Rev 25(6):e13733. https:\/\/doi.org\/10.1111\/obr.13733","journal-title":"Obes Rev"},{"issue":"4","key":"6402_CR8","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/S2213-8587(23)00385-6","volume":"12","author":"ME Lean","year":"2024","unstructured":"Lean ME, Leslie WS, Barnes AC et al (2024) 5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study. Lancet Diabetes Endocrinol 12(4):233\u2013246. https:\/\/doi.org\/10.1016\/S2213-8587(23)00385-6","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"4","key":"6402_CR9","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1007\/s00125-023-06069-1","volume":"67","author":"A Rothberg","year":"2024","unstructured":"Rothberg A, Lean M, Laferrere B (2024) Remission of type 2 diabetes: always more questions, but enough answers for action. Diabetologia 67(4):602\u2013610. https:\/\/doi.org\/10.1007\/s00125-023-06069-1","journal-title":"Diabetologia"},{"issue":"5","key":"6402_CR10","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/S2213-8587(19)30068-3","volume":"7","author":"MEJ Lean","year":"2019","unstructured":"Lean MEJ, Leslie WS, Barnes AC et al (2019) Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 7(5):344\u2013355. https:\/\/doi.org\/10.1016\/S2213-8587(19)30068-3","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"4","key":"6402_CR11","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1111\/dme.14122","volume":"37","author":"H Dambha-Miller","year":"2020","unstructured":"Dambha-Miller H, Day AJ, Strelitz J, Irving G, Griffin SJ (2020) Behaviour change, weight loss and remission of type 2 diabetes: a community-based prospective cohort study. Diabet Med 37(4):681\u2013688. https:\/\/doi.org\/10.1111\/dme.14122","journal-title":"Diabet Med"},{"issue":"12","key":"6402_CR12","doi-asserted-by":"publisher","first-page":"4147","DOI":"10.1007\/s11695-023-06909-4","volume":"33","author":"M De Luca","year":"2023","unstructured":"De Luca M, Zese M, Silverii GA et al (2023) Bariatric Surgery for Patients with Overweight\/Obesity. A comprehensive grading methodology and network metanalysis of randomized controlled trials on weight loss outcomes and adverse events. Obes Surg 33(12):4147\u20134158. https:\/\/doi.org\/10.1007\/s11695-023-06909-4","journal-title":"Obes Surg"},{"issue":"9","key":"6402_CR13","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/S2213-8587(24)00194-3","volume":"12","author":"J Valabhji","year":"2024","unstructured":"Valabhji J, Gorton T, Barron E et al (2024) Early findings from the NHS Type 2 Diabetes Path to Remission Programme: a prospective evaluation of real-world implementation. Lancet Diabetes Endocrinol 12(9):653\u2013663. https:\/\/doi.org\/10.1016\/S2213-8587(24)00194-3","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"1","key":"6402_CR14","doi-asserted-by":"publisher","first-page":"e1004327","DOI":"10.1371\/journal.pmed.1004327","volume":"21","author":"H Wu","year":"2024","unstructured":"Wu H, Yang A, Lau ESH et al (2024) 1-year weight change after diabetes diagnosis and long-term incidence and sustainability of remission of type 2 diabetes in real-world settings in Hong Kong: an observational cohort study. PLoS Med 21(1):e1004327. https:\/\/doi.org\/10.1371\/journal.pmed.1004327","journal-title":"PLoS Med"},{"issue":"Suppl 1","key":"6402_CR15","doi-asserted-by":"publisher","first-page":"S145","DOI":"10.2337\/dc24-S008","volume":"47","author":"American Diabetes Association Professional Practice Committee","year":"2024","unstructured":"American Diabetes Association Professional Practice Committee (2024) Obesity and weight management for the prevention and treatment of type 2 diabetes: standards of care in diabetes-2024. Diabetes Care 47(Suppl 1):S145\u2013S157. https:\/\/doi.org\/10.2337\/dc24-S008","journal-title":"Diabetes Care"},{"issue":"8","key":"6402_CR16","doi-asserted-by":"publisher","first-page":"e200420","DOI":"10.1001\/jamasurg.2020.0420","volume":"155","author":"RV Cohen","year":"2020","unstructured":"Cohen RV, Pereira TV, Aboud CM et al (2020) Effect of gastric bypass vs best medical treatment on early-stage chronic kidney disease in patients with type 2 diabetes and obesity: a randomized clinical trial. JAMA Surg 155(8):e200420. https:\/\/doi.org\/10.1001\/jamasurg.2020.0420","journal-title":"JAMA Surg"},{"issue":"12","key":"6402_CR17","doi-asserted-by":"publisher","first-page":"3907","DOI":"10.1007\/s11695-019-04095-w","volume":"29","author":"AD Miras","year":"2019","unstructured":"Miras AD, Ravindra S, Humphreys A et al (2019) Metabolic changes and diabetes microvascular complications 5 years after obesity surgery. Obes Surg 29(12):3907\u20133911. https:\/\/doi.org\/10.1007\/s11695-019-04095-w","journal-title":"Obes Surg"},{"issue":"3","key":"6402_CR18","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s00125-023-06048-6","volume":"67","author":"EW Gregg","year":"2024","unstructured":"Gregg EW, Chen H, Bancks MP et al (2024) Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study. Diabetologia 67(3):459\u2013469. https:\/\/doi.org\/10.1007\/s00125-023-06048-6","journal-title":"Diabetologia"},{"key":"6402_CR19","doi-asserted-by":"publisher","first-page":"e2016025","DOI":"10.4178\/epih.e2016025","volume":"38","author":"M Shakiba","year":"2016","unstructured":"Shakiba M, Soori H, Mansournia MA, Nazari SSH, Salimi Y (2016) Adjusting for reverse causation to estimate the effect of obesity on mortality after incident heart failure in the Atherosclerosis Risk in Communities (ARIC) study. Epidemiol Health 38:e2016025. https:\/\/doi.org\/10.4178\/epih.e2016025","journal-title":"Epidemiol Health"},{"key":"6402_CR20","doi-asserted-by":"publisher","first-page":"117313","DOI":"10.1016\/j.atherosclerosis.2023.117313","volume":"394","author":"A Chait","year":"2024","unstructured":"Chait A, Eckel RH, Vrablik M, Zambon A (2024) Lipid-lowering in diabetes: an update. Atherosclerosis 394:117313. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2023.117313","journal-title":"Atherosclerosis"},{"key":"6402_CR21","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2410819","author":"AM Jastreboff","year":"2024","unstructured":"Jastreboff AM, le Roux CW, Stefanski A et al (2024) Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med. https:\/\/doi.org\/10.1056\/NEJMoa2410819","journal-title":"N Engl J Med"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06402-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-025-06402-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06402-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T15:03:51Z","timestamp":1747062231000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-025-06402-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,22]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["6402"],"URL":"https:\/\/doi.org\/10.1007\/s00125-025-06402-w","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,22]]},"assertion":[{"value":"30 October 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We wish to thank S. Del Prato (Interdisciplinary Research Center \u2018Health Science\u2019, Sant'Anna School of Advanced Studies, Pisa, Italy) for useful discussions and insights.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Restrictions apply to the sharing of rough data used for this study. Aggregate data are available on reasonable request to the corresponding author.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Open access funding provided by Universit\u00e0 degli Studi di Padova within the CRUI-CARE Agreement. The study is supported by institutional grants from the University of Padova.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"MLM performed data analysis and wrote the manuscript. MR, VF, MDA and GS performed data collection and interpretation and revised the manuscript. AA contributed to study conception and design, data interpretation and manuscript revision. GPF performed data collection, analysis and interpretation and wrote the manuscript. All authors approved the final version of the manuscript for publication. GPF is the guarantor of the work and takes full responsibility for its content.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}