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Slow dose escalation mitigates these effects substantially, and discontinuation due to gastrointestinal intolerance ranges from 3% to 16% across agents, being highest for GLP-1/glucagon dual agonists (e.g., survodutide)

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In 2009, the first unimolecular gut hormone receptor co-agonist, a glucagon/GLP-1 receptor co-agonist, was discovered and validated in preclinical models [76]