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Their long\u2010term value depends on how well the weight loss is maintained and on the composition of weight loss, not only amount of weight loss. Part of incretin\u2010induced weight loss is lean tissue. It is unknown whether the proportion of lean mass, and especially, muscle mass loss is greater than with other weight\u2010loss interventions, and whether it may cause clinically meaningful harm. Men with obesity commonly have low or low\u2010normal testosterone, which is associated with reduced muscle mass, increased visceral adiposity, impaired insulin sensitivity, and increased cardiovascular risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>We propose, as an exploratory hypothesis, that in men with obesity and low testosterone, combining incretin therapy with testosterone therapy may preserve muscle mass, increase the proportion of weight lost as fat mass, and reduce fat\u2010predominant weight regain after incretin discontinuation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Resistance exercise and adequate protein intake are first\u2010line measures for preserving muscle mass during weight loss. No lifestyle measure reliably prevents the fat\u2010predominant weight regain that follows diet discontinuation, and long\u2010term adherence to lifestyle interventions is poor. We position testosterone therapy as a pharmacological adjunct for weight loss maintenance in men with obesity and low testosterone, to be evaluated in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The only direct human data come from a small, non\u2010randomized pilot study and are hypothesis\u2010generating. The clinical consequences of incretin\u2010associated loss of lean mass, and particularly muscle mass, should be investigated in future studies. The hypothesis requires evaluation in randomized controlled trials that properly assess changes in lean mass and muscle mass, along with safety monitoring, before it can inform clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71384","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:05:23Z","timestamp":1792461923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Weight Regain After Incretin Treatment: The Lean Mass Deficit Hypothesis and a Role for Testosterone Combination Therapy in Men"],"prefix":"10.1111","author":[{"given":"Michael","family":"Zitzmann","sequence":"first","affiliation":[{"name":"Department of Clinical and Surgical Andrology, Centre of Reproductive Medicine and Andrology (CeRA) M\u00fcnster University Hospital (UKM)  M\u00fcnster 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