Customized GLP-1 Retatrutide Tirzepatide Semaglutide Liraglutide for Treatment of Diabetes and Obesity

What is Semaglutide?
Semaglutide is the newest GLP-1R agonist and was approved by the FDA as a once-weekly injection for the treatment of T2DM in late 2017. The peptide is chemically similar to liraglutide, with the inclusion of two structural modifications (Lau, Bloch, et al., 2015). The first is the replacement of Gly with the non-proteinogenic amino acid 2-aminoisobutyric acid (Aib) at position 2. The second is the attachment of octadecanoic diacid to the side chain of Lys-26 through a short polyethylene glycol (PEG) spacer and a γ-glutamic acid linker. The amino acid substitution renders the peptide more resistant to DPP-4 compared to liraglutide, and the presence of the 18-carbon fatty acid moiety results in a high binding affinity for serum albumin, which translates to a half-life of approximately 7 days in humans. 

Semaglutide is a long-acting GLP-1 receptor agonist (GLP-1RA). GLP-1RA activates the GLP-1 receptor by mimicking natural GLP-1, enhances insulin secretion in a glucose-dependent manner, inhibits glucagon secretion, delays gastric emptying, and reduces food intake through central appetite suppression, thereby reducing blood sugar and weight loss. GLP-1RA not only has significant hypoglycemic effect, but also has a small risk of hypoglycemia when used alone. At the same time, GLP-1RA has the effects of weight loss, blood pressure reduction, and improvement of blood lipid profile, so it has become one of the world's best-selling hypoglycemic drugs.

Application of Semaglutide:
1.Significant hypoglycemic effect. Subcutaneous injection of semaglutide once a week has a significant advantage in lowering blood glucose compared to various standard hypoglycemic therapies commonly used in clinical practice.
2.The weight loss effect is obvious. Obese patients treated with semaglutide lost an average of 17-18% of their body weight over 68 weeks, and the trial was shown to be safe and well tolerated.
3.In addition to its significant hypoglycemic effect, Semaglutide has a significant benefit on cardiovascular outcomes in patients with type 2 diabetes, significantly reducing the risk of major cardiovascular adverse events by 26%, significantly reducing the risk of non-fatal stroke by 39%, and significantly improving the patient's weight, blood pressure, lipid and other indicators. It can bring comprehensive cardiovascular and metabolic benefits to patients.