{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:07:32Z","timestamp":1791644852761,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Japan's optimal use guideline restricts insurance\u2010reimbursed GLP\u20101 receptor agonist (GLP\u20101 RA) therapy for obesity to patients completing a mandatory 6\u2010month lifestyle intervention, caps treatment at 68\u2009weeks (semaglutide 2.4\u2009mg) or 72\u2009weeks (tirzepatide), and mandates subsequent washout. We evaluated the clinical implications of this regulated program in a real\u2010world cohort of patients with obesity treated with semaglutide or tirzepatide, with particular attention to pre\u2010treatment weight change during the mandated lifestyle phase, on\u2010treatment response, and post\u2010cessation weight regain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We prospectively followed 104 patients with obesity without type 2 diabetes (45 primary, 59 post\u2010metabolic\/bariatric\u2010surgery rescue) treated with semaglutide (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200943) or tirzepatide (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200961) under Japan's optimal use guideline. Both cohorts qualified for GLP\u20101 RA under the same insurance eligibility criteria (BMI \u2265\u200927\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      with obesity\u2010related comorbidities). Body weight was recorded bimonthly from 6\u2009months before drug initiation through the post\u2010cessation washout phase. Outcomes included percent body weight change from baseline and rates of weight loss and regain across phases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During the mandated lifestyle phase, the rescue cohort gained weight (+2.28\u2009\u00b1\u20094.16\u2009kg; 69% gained weight), while the primary cohort remained essentially stable (\u22120.65\u2009\u00b1\u20095.51\u2009kg;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004). Once GLP\u20101 RA was initiated, % body weight change trajectories were comparable between cohorts from month 4 onward (month 6: \u221211.8% vs. \u221210.8%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.57). Aggregate % body weight change reached a partial plateau by months 10\u201314 (\u221216.3%, \u221216.1%, \u221215.5%) and was \u221216.0% at the treatment endpoint (month 16,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930, all semaglutide\u2010treated). After mandated cessation, 95% (21\/22) of patients regained weight by 2\u2009months, and 83% (10\/12) by 6\u2009months. Indexed to month \u22126, mean change reverted from \u221214.4% at month 16 to \u22127.0% at month 22, indicating substantial loss of achieved treatment benefit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Under Japan's current regulatory framework, GLP\u20101 RAs produced comparable weight loss in primary and rescue cohorts sharing the same eligibility criteria. Phase\u2010specific observations\u2014pre\u2010treatment weight gain in the rescue cohort and achieved treatment effect that reverted rapidly after mandated cessation\u2014provide a real\u2010world basis for examining whether mandated treatment cessation is compatible with the chronic nature of obesity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71190","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:31:48Z","timestamp":1785897108000},"page":"9595-9606","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>GLP<\/scp>\n                    \u20101 Receptor Agonist Therapy for Obesity Under Japan's Optimal Use Guideline: A Prospective Real\u2010World Study of Lifestyle Pre\u2010Treatment, Time\u2010Limited Treatment Cap, and Post\u2010Cessation Regain"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4917-4545","authenticated-orcid":false,"given":"Susumu","family":"Inamine","sequence":"first","affiliation":[{"name":"Center for Metabolic and Bariatric Surgery Ohama Daiichi Hospital  Naha Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-8066","authenticated-orcid":false,"given":"Yasunori","family":"Uesato","sequence":"additional","affiliation":[{"name":"Center for Metabolic and Bariatric Surgery Ohama Daiichi Hospital  Naha Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.12551"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP161365.GL"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-3415"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032183"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206038"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307563"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ23-0593"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15638"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40519-021-01217-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2023.2930"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11695-025-08210-y"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40519-025-01770-z"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02026-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.3224"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2410819"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.24945"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2025.6112"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14725"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.24310"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2404881"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2401943"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2025.09.019"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2018.10.014"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2023.02.003"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-022-01176-2"}],"container-title":["Diabetes, 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