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For non-diabetic obesity, the cleanest comparison is between two separate trials: STEP 1 (semaglutide 2.4 mg, Wilding et al., NEJM 2021): 14.9% body weight loss at 68 weeks SURMOUNT-1 (tirzepatide 15 mg, Jastreboff et al., NEJM 2022): 20.9% body weight loss at 72 weeks A roughly 6 percentage point gap in average weight loss favors tirzepatide

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MOTS-C MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a naturally occurring peptide encoded within mitochondrial DNA, playing a key role in cellular metabolism and energy regulation

Additionally, GPER influences the expression of bone metabolism-associated genes such as Runx2 and osteocalcin through downstream signaling pathways, including cAMP/PKA and AMPK, promoting osteoblast activity and suppressing osteoclast-mediated bone resorption