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The beneficial effects of GLP-1 RAs on HRQoL and other outcomes in HFpEF are likely due to pleiotropic impacts, related or not to weight reduction, such as decongestion (mainly due to the reduction of increased plasma volume associated with obesity and epicardial constrain), reverse cardiac remodelling (mainly due to the decrease in epicardial fat and regression of left atrial and LV myopathy, lowering intracardiac pressure) and anti-inflammatory actions, among others

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The same problem-solving framework applies to retatrutide, with the additional consideration that glucagon receptor effects on energy expenditure may help break plateaus that dual agonists cannot