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4 Discussion The main findings of the present studies are the following: (1) the pharmacokinetics of icodec are unchanged when combining icodec and semaglutide in IcoSema, (2) the total exposure of semaglutide in IcoSema is unchanged, but the maximum concentration is higher and earlier compared with semaglutide administration alone, (3) the change in semaglutide pharmacokinetics in IcoSema appears to be owing to competition for albumin binding locally at the injection site, where icodec outcompetes semaglutide and (4) the frequency of gastrointestinal related adverse events is higher for IcoSema versus icodec or semaglutide administration alone

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