Semaglutide

Mechanism (as reported)

A study describing discovery/research design reports that semaglutide was selected for once-weekly GLP-1 analogue development by increasing albumin affinity and securing stability against metabolic degradation, with semaglutide having amino-acid substitutions versus human GLP-1 and being derivatized (PMID 26308095).

Key findings (each cites a source)

• A phase 3 trial in patients with type 2 diabetes reported that semaglutide (once weekly) was associated with an estimated mean change in glycated hemoglobin from baseline to 40 weeks of -1.86 percentage points (in the trial comparing tirzepatide versus semaglutide). [PMID 34170647]
• In the same type 2 diabetes phase 3 trial (tirzepatide vs semaglutide), gastrointestinal adverse events were reported as the most common adverse events, and the study described them as primarily mild to moderate in severity. [PMID 34170647]
• A preclinical/biophysical design study reported semaglutide was selected as an optimal once-weekly candidate for a GLP-1 analogue by increasing albumin affinity and ensuring stability against metabolic degradation, and it reports semaglutide has two amino acid substitutions versus human GLP-1 plus derivatization at lysine 26. [PMID 26308095]
• The semaglutide discovery/PK design study reported semaglutide plasma half-life of 46.1 h in mini-pigs after i.v. administration and that semaglutide had an MRT of 63.6 h after s.c. dosing to mini-pigs. [PMID 26308095]
• A review of semaglutide safety reported that semaglutide induces mostly mild-to-moderate and transient gastrointestinal disturbances and increases the risk of biliary disease (cholelithiasis), and stated no unexpected safety issues had arisen to date in the context described. [PMID 34305810]