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These challenges were ultimately overcome through molecular modification, long-acting formulations, and a more sophisticated understanding of receptor pharmacology, including biased agonism and doseexposure relationships ( This historical trajectory strongly suggests that GLP-1 should not be viewed as an isolated success, but rather as a prototype for a much larger class of peptidereceptor systems whose translational potential remains unrealized

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The complete search strategies tailored for each database are provided in Supplementary Materials 1

In the lower two-thirds of the oesophagus, including the thoracic and abdominal parts containing the lower oesophageal sphincter, both layers are composed of smooth muscle

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