“…It is clear that OT is effective as a monotherapy to elicit weight loss in DIO rodents ( Deblon et al, 2011 ; Maejima et al, 2011 , 2017 ; Zhang and Cai, 2011 ; Zhang et al, 2011 ; Morton et al, 2012 ; Blevins et al, 2016 ; Roberts et al, 2017 ; Edwards et al, 2021b ), non-human primates ( Blevins et al, 2015 ) and humans ( Zhang et al, 2013 ), but these effects (pre- vs. post-intervention) appear to be modest even after sustained treatments that last 4–8 weeks [≈ 4.9% in DIO mice ( Roberts et al, 2017 ), 8.7% in DIO rats ( Roberts et al, 2017 ), 3.3% in DIO rhesus monkeys ( Blevins et al, 2015 ) and 9.3% humans based on results from a proof of concept study with short duration and small sample size ( Zhang et al, 2013 )]. The average weight loss with the currently FDA approved medications (i.e., orlistat, liraglutide, naltrexone/bupropion, phentermine/topiramate, semaglutide) ranges between 5 and 14.9% ( Allison et al, 2012 ; Apovian et al, 2015 ; Bray et al, 2018 ; Enebo et al, 2021 ).…”