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GLP1s reach into both systems

One notable example is orforglipron (LY3502970), a small molecule in Phase III trial, binds to GLP-1R at a distinct site closer to the extracellular side of the transmembrane helical bundle rather than deeply within the orthosteric pocket (Kawai et al., 2020

The trial involving 18,000 people not yet published as of September 2023 is apparently the first to show that GLP-1 drugs can confer heart health benefits for people who are overweight but don't have diabetes

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