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Pain and Physical Function Improvements TRIUMPH-4's co-primary endpoint focused on knee osteoarthritis pain, measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale: WOMAC Pain Score Reductions: Retatrutide 9mg: -4.5 points (75.8% reduction) Retatrutide 12mg: -4.4 points (73.3% reduction) Placebo: -2.4 points (40.3% reduction) Participants also experienced substantial improvements in physical function, with WOMAC physical function subscale scores improving by: Retatrutide 9mg: -4.1 points Retatrutide 12mg: -4.2 points Placebo: -2.1 points Perhaps most remarkably, a post-hoc analysis revealed that 14.1% of participants on 9mg and 12.0% on 12mg became completely pain-free at 68 weeks, compared to just 4.2% on placebo

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Intravenous administration in mice showed that NRH is more potent at raising NAD + levels in the liver and muscle than NR and NMN 128

Finally, this unique phenotype offers mechanistic insights: the dissociation between severe adiposity and a favorable cardiometabolic profile suggests that MC4R signaling plays a non-redundant role in integrating energy balance with cardiovascular regulation [2,32,33]