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Clinical data so far have shown that retatrutide dose-dependently increases heart rate up to 6.7 bpm at 24 weeks and declined thereafter ( Figure 2 Importantly, in the SELECT trial, differences in rates of cardiovascular events between semaglutide and placebo began to emerge within the first few months suggesting that weight loss alone may not account for the full benefits ( On the co-morbidities front, GLP-1R is not expressed in the liver and the data generated with semaglutide in NASH patients seems to support a lack of a direct antifibrotic effect ( There is also tremendous activity in the development of non peptidic small molecules targeting the incretin system to produce drugs that are orally available