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Semaglutide has 94% homology to native GLP1, with structural modifications that make semaglutide less susceptible to degradation by dipeptidyl peptidase4 (DPP4) enzymes.7 Moreover, the modifications improve the specific highaffinity binding to albumin,7 which slows down the degradation of semaglutide in plasma and results in decreased renal clearance.8 The structural modifications prolong the halflife of semaglutide to ~1 week, making it appropriate for onceweekly administration.7, 9 In phase III trials, semaglutide demonstrated superior reductions in HbA1c and body weight compared with placebo and active comparators,10, 11, 12 as well as a decrease in cardiovascular risk.13 Native GLP1 is rapidly metabolized by enzymes such as DPP4, which is found in many tissues and cell types.14 Clearance of native GLP1 and its metabolites is largely mediated via the kidneys14 and, in general, GLP1RAs require no dose adjustment for hepatic impairment.15 In humans, semaglutide is metabolized via proteolytic cleavage of the peptide backbone and sequential oxidation of the fatty acid chain, with no single organ acting as the major route of elimination.8 Semaglutide degradation products are excreted via urine and faeces,8 implying at least partial involvement of the liver in semaglutide elimination

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