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Importantly, some patients taking the highest dose of oral semaglutide in trials achieved up to 22% weight loss, bringing results closer to what has previously only been associated with injectable GLP-1 treatments

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Indeed, GLP-1R blockade by direct injection of exendin(9-39) into the ARC abolished the weight loss effects of liraglutide, whereas neither injection of exendin(9-39) into the PVN nor electrolytic lesion of the PVN affected the ability of liraglutide to reduce weight gain in rats

There is a weak to modest weight loss effect with berberine as reported in small and short duration studies