{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T12:07:04Z","timestamp":1794226024339,"version":"4.8.0"},"reference-count":120,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Highly effective anti\u2010obesity medications (AOMs) induce substantial weight loss and have renewed debate on appropriate treatment targets. Weight loss comprises reductions in fat mass (FM) and fat\u2010free mass (FFM), with skeletal muscle (SM) as the major component of FFM. Clinical trials report that 20%\u201340% of total weight loss is attributable to FFM, raising concerns about excessive SM loss and sarcopenia risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This narrative review integrates physiological principles and quantitative data from clinical trials to derive a rationale for redefining healthy weight loss targets based on body composition. Determinants of energy partitioning (baseline adiposity, age, diet and physical activity) are combined with predictive and reference\u2010based approaches. Skeletal muscle index (SMI) was estimated from FFM, body weight, sex and age (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.87, SEE\u2009=\u20090.635\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) and evaluated using SMI standard deviation scores (SDS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SM accounts for 92%\u201397% of FFM loss during weight reduction. In incretin\u2010based trials, FM decreased by \u221218.7% to \u221233.9% and FFM by \u22126.8% to \u221210.9%, corresponding to 33%\u201338% of total weight loss. Model\u2010based estimates predict lower FFM reductions (~6.8%\u20136.9%), indicating that observed FFM losses exceed physiological expectations under conditions of large energy deficits. Across studies, diet\u2010 or AOM\u2010induced weight loss without structured exercise is associated with higher proportions of FFM loss than expected, whereas interventions including exercise show more favourable partitioning. An SMI\u2010SDS threshold of \u22120.67 (25th percentile) identifies clinically relevant SM depletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Disproportionate SM loss is common with considerable weight reduction and may exceed physiologically expected levels. An SMI\u2010based framework enables definition of individualized, safe treatment targets and may help prevent sarcopenia during obesity treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70334","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:43:42Z","timestamp":1784123022000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Defining Healthy Weight Loss and Target Weight in the Era of Highly Effective Treatment of Patients With Obesity"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8318-9448","authenticated-orcid":false,"given":"Anja","family":"Bosy\u2010Westphal","sequence":"first","affiliation":[{"name":"Department of Human Nutrition, Institute of Human Nutrition and Food Science Kiel University  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0483-860X","authenticated-orcid":false,"given":"Janna","family":"Enderle","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Institute of Human Nutrition and Food Science Kiel University  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Norman","sequence":"additional","affiliation":[{"name":"German Institute of Nutritional Science, University of Potsdam, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam\u2010Rehbr\u00fccke  Nuthetal Germany"},{"name":"Department of Geriatrics and Medical Gerontology, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred J.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Institute of Human Nutrition and Food Science Kiel University  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102214"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.6586"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvae164"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.067676"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(24)00272-9"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.156113"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13190"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03095-3"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.090167"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140553"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20230586"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.016"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnaa016"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00641-2"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.582258"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12502"},{"issue":"3","key":"e_1_2_5_18_1","first-page":"318","article-title":"Pathogenesis of NIDDM","volume":"15","author":"DeFronzo R. 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