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Setmelanotide is FDA approved for ages 6 years and older to treat monogenic obesity due to variants that are pathogenic, likely pathogenic or variant of unknown significance (VUS) in POMC (pro opiomelanocortin), PCSK1 (proprotein convertase subtilisin/kexin type 1), LEPR (leptin receptor) and Bardet Biedl Syndrome (BBS)

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For instance, replacing problematic functional groups, such as the carboxylic acid group in danuglipron, with alternative structures has shown promise

doi: 10.1001/jamacardio.2020.4511 68 VaduganathanMDochertyKFClaggettBLJhundPSde BoerRAHernandezAFet al

however, no improvement in fibrosis was found (52)