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In the lean stack protocol , it functions as the metabolic regulator by: Activating GLP-1 receptors to suppress appetite and slow gastric emptying Activating GIP receptors to enhance insulin sensitivity in adipose tissue Activating glucagon receptors to increase energy expenditure and fat oxidation Reducing body weight through combined anorectic and thermogenic effects Improving glycaemic control in metabolic research models Retatrutide has demonstrated the most significant weight reduction of any incretin-based compound in Phase 2 clinical data, with mean reductions of 24.2% over 48 weeks at the highest dose making it the centrepiece of the lean stack protocol

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160,161 For example, HM15211, a triple agonist developed by Hanmi Pharmaceutical in South Korea that activates GLP-1R, GIPR and GCGR has entered early clinical trials for the treatment of obesity and non-alcoholic steatohepatitis (NASH)