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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

ANSWER: Meta-analyses evaluating the A1C-lowering impact of adding a DPP-4 inhibitor or SGLT2 inhibitor to metformin have shown either no significant differences between the two classes or a small difference (0.11% to 0.17%) in favour of SGLT2 inhibitors

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