Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, that’s available in monotherapy in oral or injectable form. 

GLP-1 is one of the major incretin (gut peptide secreted after nutrient intake) hormones in humans. It plays a pivotal role in many different mechanisms within the body:

• Insulin secretion
• Inhibits glucagon release (glucagon is secreted as a response in blood sugar drop)
• Suppresses hepatic gluconeogenesis (glycogen is the primary carbohydrate stored in the liver)
• Delays gastric emptying
• Reduces appetite and energy intake

When talking about obese diabetic 2 type patients, GLP-1 assumes a special status in their treatment as it lowers HbA1c levels along with body weight, but without the risk of hypoglycemia. 

However, the biggest problem with GLP-1 is its short half-live (of only 1 to 2 minutes) and this is why researchers turner to various other GLP-1 receptor agonists, such as liraglutide, dulaglutide and, of course, semaglutide. Another thing researchers hope to achieve by turning to GLP-1 agonists, such as semaglutide, is to develop an effective diabetes management drug which needs less frequent dosing. 

Murine models suggested that semaglutide’s GLP-1 receptor activation affects insulin secretion, blood sugar homeostasis and beta cell protection. Further, in vitro studies showed its potential to also affect glucagon secretion. This insulin glucagon mechanics is what’s used to balance our pancreatic function and regulate metabolism. 

References:

1. Mahapatra MK, Karuppasamy M, Sahoo BM. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Rev Endocr Metab Disord. 2022 Jun;23(3):521-539. doi: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID: 34993760; PMCID: PMC8736331.
2. Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012 Dec;8(12):728-42. doi: 10.1038/nrendo.2012.140. Epub 2012 Sep 4. PMID: 22945360.