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This is particularly noteworthy because two competing oral small-molecule GLP-1 programs from Pfizer, lotiglipron (discontinued in 2023) and danuglipron (discontinued in April 2025), were terminated due to liver toxicity concerns

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Gut and systemic GLP-1 resistance have been previously described in HFD-fed mice, associated with dysglycemia, insulin resistance, increased food intake, and impaired gastric emptying, and attributed to an acquired impairment of the gut-brain axis secondary to intestinal dysbiosis (34)