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Each pathway contributes a separate pharmacological signal: GLP-1 receptor agonism slows gastric emptying and reduces appetite signalling in the hypothalamus GIP receptor agonism enhances glucose-dependent insulin secretion and is associated in the literature with effects on lipid handling Glucagon receptor agonism increases energy expenditure and hepatic glucose output, the opposite direction to a glucagon antagonist, and is absent from every dual agonist currently on the UK market How retatrutide compares to dual agonists Tirzepatide (Mounjaro) is a GIP + GLP-1 dual agonist authorised by the MHRA for type 2 diabetes in 2023

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An interruption of just six months before resuming treatment still reduced the cardiovascular benefit, leading to a 4% to 8% increase in risk, compared to continuous use

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