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Some heterozygous patients can have normal biochemistry, but patients with OTC deficiency will often have elevated glutamine, elevated alanine, decreased or absent citrulline, elevated urine orotic acid

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While Mc4r KO mice treated with PL7737 showed no significant decline in food intake or weight, DIO mice treated with PL7737 demonstrated significantly reduced food intake and significantly reduced body weight by 7.06% compared to the vehicle group, confirming the metabolic effects of PL7737 require intact MC4R signaling

Taken together, these heterogeneous findings highlight both biological plausibility and the methodological constraints that shape the current evidence base, motivating the integrative Discussion below

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Glucagon-like peptide-1 receptor co-agonists for the treatment of metabolic disease