{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:19:43Z","timestamp":1768569583456,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,27]]},"group-title":"Endocrinology (including Diabetes Mellitus and Metabolic Disease)","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Lipodystrophy encompasses a group of rare disorders associated with severe metabolic disease. These disorders are defined by abnormal fat distribution, with near-total (generalized lipodystrophy, GL) or partial (partial lipodystrophy, PL; i.e. familial partial lipodystrophy, FPLD) absence of adipocyte mass leading to a decreased ability to store lipids safely. Excess lipids are more likely to be stored in non-adipose tissues, which leads to the metabolic manifestations. We have recently shown that glucagon-like peptide-1 agonists are associated with metabolic improvements in FPLD. We hypothesized that tirzepatide, a dual incretin, may also lead to metabolic improvement in patients with lipodystrophy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Observational cohort of patients with PL or GL who received tirzepatide clinically were tracked in the context of ongoing natural history studies.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Seventeen patients received tirzepatide, 14 with FPLD (ages within 30-74 years; 12 female 2 male). After a median 8.7 months of follow-up, BMI (median\u0394 -1.7; range -5.9 to 0.9 kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ;\n                    <jats:italic>p<\/jats:italic>\n                    =0.008), HbA1c (median\u0394 -1.1%; range -6.3 to -0.1%;\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.001), triglycerides [median\u0394 - 65 mg\/dL (-0.73 mmol\/L); range -3820 to 43 mg\/dL (-43.2 to 0.49 mmol\/L);\n                    <jats:italic>p<\/jats:italic>\n                    =0.003] and total daily insulin requirements (median\u0394 -109; range -315 to 0 units\/day;\n                    <jats:italic>p<\/jats:italic>\n                    =0.002) were significantly reduced. Three patients with acquired GL (Ages within 35-64 years; all female) also demonstrated a robust response to tirzepatide with reduced BMI (22.2-&gt;20.9; 26.2-&gt;25.4; 19.5-&gt;17.6 kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    ), HbA1c (8.5%-&gt;7.0%; 10.2%-&gt;7.8%; 9.1%-&gt;6.5%), triglycerides (91-&gt;80; 641-&gt;293; 1238-&gt;100 mg\/dL or 1.03-&gt;0.90; 7.24-&gt;3.31; 14.0-&gt;1.13 mmol\/L), and total daily insulin requirement (85-&gt;0; 0-&gt;0; 1000-&gt;750 units\/day). Three patients did not tolerate dose escalation due to gastroesophageal reflux.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Tirzepatide may be an effective treatment for patients with lipodystrophy.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.25.24313345","type":"posted-content","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T14:50:15Z","timestamp":1727448615000},"source":"Crossref","is-referenced-by-count":1,"title":["Tirzepatide for Lipodystrophy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-5049","authenticated-orcid":false,"given":"Rasimcan","family":"Meral","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Merve","family":"Celik Guler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diarratou","family":"Kaba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeevitha","family":"Prativadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric D","family":"Frontera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-1125","authenticated-orcid":false,"given":"Maria Cristina","family":"Foss-Freitas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noura","family":"Nachawi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David T","family":"Broome","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marissa","family":"Lightbourne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca J","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeon I","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9171-1144","authenticated-orcid":false,"given":"Elif A","family":"Oral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024100104000737000_2024.09.25.24313345v1.1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1159"},{"key":"2024100104000737000_2024.09.25.24313345v1.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2466"},{"key":"2024100104000737000_2024.09.25.24313345v1.3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031868"},{"key":"2024100104000737000_2024.09.25.24313345v1.4","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1872"},{"key":"2024100104000737000_2024.09.25.24313345v1.5","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00032.2020"},{"key":"2024100104000737000_2024.09.25.24313345v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.007"},{"key":"2024100104000737000_2024.09.25.24313345v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13311"},{"key":"2024100104000737000_2024.09.25.24313345v1.8","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab216"},{"key":"2024100104000737000_2024.09.25.24313345v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2024.05.015"},{"key":"2024100104000737000_2024.09.25.24313345v1.10","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1359211"},{"key":"2024100104000737000_2024.09.25.24313345v1.11","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.16.1568"},{"key":"2024100104000737000_2024.09.25.24313345v1.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2005.00468.x"},{"key":"2024100104000737000_2024.09.25.24313345v1.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012437"},{"key":"2024100104000737000_2024.09.25.24313345v1.14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200215001"},{"key":"2024100104000737000_2024.09.25.24313345v1.15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1546"},{"key":"2024100104000737000_2024.09.25.24313345v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1502-9"},{"key":"2024100104000737000_2024.09.25.24313345v1.17","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-1589-1"},{"key":"2024100104000737000_2024.09.25.24313345v1.18","unstructured":"Parks MH . 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