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Unlike older weight loss drugs that target a single hormone pathway, retatrutide activates three separate receptors: GLP-1 (glucagon like peptide 1), which slows digestion and reduces appetite GIP (glucose dependent insulinotropic polypeptide), which helps regulate blood sugar and insulin release Glucagon, which increases energy expenditure and supports fat burning By working on all three pathways together, retatrutide aims to produce a stronger combined effect than medicines that only target one or two of these hormones, such as semaglutide or tirzepatide

10.1016/S2213-8587(19)30066-X Summary Keywords glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors, combination therapy, type 2 diabetes mellitus, meta-analysis Citation Li C, Luo J, Jiang M and Wang K (2022) The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

in Metabolism used a similar protocol and found smaller but directionally consistent results, with the strongest effect in participants who started with metabolic syndrome

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Other Rare Reactions Severe skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis are extremely rare but possible