how is semaglutide synthesized synthesis Solid-Phase of Semaglutide: Using Novel Fragment Coupling Strategy to Overcome Aggregation, Improve yield and Quality The 6 Billion Dollar Synthesis

Holst JJ, Physiol Rev 87:1409-39, 2007 Drucker FJ, Cell Metab 135-165, 2006 INSULIN SECRETION PKA IC Ca++ MOLECULAR ACTIONS OF GLP-1 ON BETA CELL Insulin Secretion cAMP Epac2 PI-3K INSULIN GENE TRANSCRIPTION Pdx-1 replenishes beta cell insulin stores prevents beta cell exhaustion BETA CELL GLUCOSE SENSITIVITY increased GLUT2 and Glucokinase restores glucose responsitivity to resistant beta cells INSULIN RESPONSES TO PHYSIOLOGICALAND PHARMACOLOGICAL LEVELS OF GLP-1 Pharmacological GLP-1 levels2(15 mM hyperglycemic clamp) Physiological GLP-1 levels1(15 mM hyperglycemic clamp) 6000 6000 GLP-1 infusion-0.5 pmol/kg/min GLP-1 infusion-1.0 pmol/kg/min Plasma GLP-1: 46 pM Healthy controls 4000 4000 Insulin (pmol/L) Insulin (pmol/L) Plasma GLP-1:126 pmol/L Type 2 diabetes 2000 2000 Plasma GLP-1:41 pM Type 2 diabetes 0 0 0 60 120 0 60 120 Time (min) Time (min) 1

Not everyone needs glutathione supplementation

Cardiovascular exercise burns calories

Summary Compounded semaglutide does not have a universal refrigerated shelf life

The drug was slow to garner attention within or outside of gastroenterology

3.7 Gastrointestinal disorder A healthy diverse microbiome helps maintain a strong intestinal barrier while dysbiosis in gut microbiome leads to leaky gut, allowing pathogens and food antigens to cross the barrier and trigger immune response which further leads to inflammation