{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T11:00:31Z","timestamp":1774868431588,"version":"3.50.1"},"reference-count":12,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, induces substantial weight loss in patients with obesity; however, pharmacologically induced weight reduction may be accompanied by losses in fat-free mass (FFM), muscle strength (MS), and resting metabolic rate (RMR), potentially influencing metabolic health. The metabolic implications of short-term preservation of metabolically active tissue during TZP therapy remain incompletely characterized. Methods: We performed a secondary, exploratory analysis of a previously published 12-week prospective, non-randomized comparative study including 60 patients with obesity treated with TZP (n = 30 TZP+Low Energy Ketogenic Therapy [LEKT]; n = 30 TZP+Low Calorie Diet [LCD]). Body weight (BW), fat mass (FM), FFM, MS, and RMR were assessed at baseline and week 12. Glycaemic parameters included fasting glucose, insulin, hemoglobin A1c (HbA1c), and HOMA-IR. All analyses were exploratory and hypothesis-generating. Results: Both groups achieved comparable reductions in BW after 12 weeks. FM decreased in both groups, while relative preservation of FFM, MS, and RMR was observed in one dietary context. Short-term changes in HbA1c, insulin, and HOMA-IR were statistically associated with concurrent changes in FFM, MS, and RMR, whereas no consistent associations were observed with changes in total BW or FM. Baseline glycaemic values were largely within the normoglycemic range. Conclusions: In this short-term secondary exploratory analysis, preservation of metabolically active tissue during TZP therapy was associated with concurrent glycaemic profiles, whereas no consistent associations were observed with total weight loss magnitude. These findings do not imply causality and should be interpreted as hypothesis-generating, warranting confirmation in larger, randomized, long-term studies.<\/jats:p>","DOI":"10.3390\/nu18071092","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:57:24Z","timestamp":1774864644000},"page":"1092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Short-Term Associations Between Fat-Free Mass Preservation and Glycaemic Markers During Tirzepatide Therapy: A Secondary Exploratory Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3639-6847","authenticated-orcid":false,"given":"Luigi","family":"Schiavo","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biagio","family":"Santella","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Mingo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Baronissi, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Rossetti","sequence":"additional","affiliation":[{"name":"General and Bariatric Surgery Unit, Abano Terme Policlinic, 35031 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Orio","sequence":"additional","affiliation":[{"name":"Medical and Diabetological Center CMSO, 84123 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-4770","authenticated-orcid":false,"given":"Luigi","family":"Cobellis","sequence":"additional","affiliation":[{"name":"Unit of General Surgery, Casa Di Cura \u201cProf. Dott. Luigi Cobellis\u201d, 84078 Vallo Della Lucania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Cobellis","sequence":"additional","affiliation":[{"name":"Unit of General Surgery, Casa Di Cura \u201cProf. Dott. Luigi Cobellis\u201d, 84078 Vallo Della Lucania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Pilone","sequence":"additional","affiliation":[{"name":"Public Health Department, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100175","DOI":"10.1016\/j.obpill.2025.100175","article-title":"Chronicity of obesity and the importance of early treatment to reduce cardiometabolic risk and improve body composition","volume":"15","author":"Christensen","year":"2025","journal-title":"Obes. Pillars"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S2213-8587(24)00316-4","article-title":"Definition and diagnostic criteria of clinical obesity","volume":"13","author":"Rubino","year":"2025","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.pcd.2025.03.008","article-title":"The promise of tirzepatide: A narrative review of metabolic benefits","volume":"19","author":"Sokary","year":"2025","journal-title":"Prim. Care Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tian, Q., Song, Y., Deng, Y., and Lin, S. (2025). Efficacy and safety of tirzepatide for weight loss in patients with obesity or type 2 diabetes: A systematic review and meta-analysis. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1593134"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Reytor-Gonz\u00e1lez, C., Campuzano-Donoso, M., Sarno, G., Montalvan, M., Horowitz, R., Rossetti, G., Pilone, V., Barrea, L., Muscogiuri, G., and Schiavo, L. (2026). Single vs. Dual Agonist Pharmacotherapy for Managing Insufficient Weight Loss and Weight Regain Following Metabolic and Bariatric Surgery: A Comparative Review. Nutrients, 18.","DOI":"10.3390\/nu18040553"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide Once Weekly for the Treatment of Obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S0140-6736(23)01200-X","article-title":"Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial","volume":"402","author":"Garvey","year":"2023","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.1038\/s41591-023-02597-w","article-title":"Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: The SURMOUNT-3 phase 3 trial","volume":"29","author":"Wadden","year":"2023","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1001\/jama.2023.24945","article-title":"Continued Treatment with Tirzepatide for Maintenance of Weight Reduction in Adults with Obesity: The SURMOUNT-4 Randomized Clinical Trial","volume":"331","author":"Aronne","year":"2024","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.2337\/dbi25-0003","article-title":"High-Quality Weight Loss in Obesity: Importance of Skeletal Muscle","volume":"74","author":"Harper","year":"2025","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1161\/CIRCRESAHA.125.325532","article-title":"Unraveling Skeletal Muscle Insulin Resistance: Molecular Mechanisms and the Restorative Role of Exercise","volume":"137","author":"Whytock","year":"2025","journal-title":"Circ. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.3390\/nu17071216","article-title":"Preliminary Evidence Suggests That a 12-Week Treatment with Tirzepatide Plus Low-Energy Ketogenic Therapy Is More Effective than Its Combination with a Low-Calorie Diet in Preserving Fat-Free Mass, Muscle Strength, and Resting Metabolic Rate in Patients with Obesity","volume":"17","author":"Schiavo","year":"2025","journal-title":"Nutrients"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T10:08:11Z","timestamp":1774865291000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/7\/1092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":12,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["nu18071092"],"URL":"https:\/\/doi.org\/10.3390\/nu18071092","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]}}}