Weight Loss Drug: semaglutide)
Overview of molecular structure
Semaglutide requires a prescription and is marketed under the brand names Ozempic, Wegovy, and Rybelsus.
It contains a dicarboxylic fatty acid molecule linked to peptide based on the hormone, produced by the digestive system, glucagon-like peptide-1 (GLP-1);
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption.
GLP-1 is an incretin; thus, it has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin.
the peptide been shown to interact with the cell membranes and membrane receptors. The peptide contains 2-aminoisobutyric acid, which is not a natural amino acid; but is similar in structure to another prescribed weight loss drug, phentermine.
Isoleucine (only 1 in sequence) in peptide is important for binding...
Semaglutide has unique specificity, given that the incorporated hormone peptide naturally interacts with transmembrane receptors in the gut.
Semaglutide is a 31-amino acid peptide with specific modifications: Ala8→Aib, Lys26 acylation with a C18 fatty diacid, and Lys34→Arg.
Amino Acid Sequence
Semaglutide is based on human GLP-1 (7-37) but includes three key modifications to enhance stability and prolong half-life. Using single-letter amino acid codes, the sequence from N-terminus to C-terminus is:
H-Aib-E-G-T-F-T-S-D-V-S-S-Y-L-E-G-Q-A-A-K(E-C18 fatty diacid)-E-F-I-A-W-L-V-K-R-G
Mechanism of action
Semaglutide contains a digestive hormone amino acid sequence that will hone it to gut membrane receptors with optimal accuracy. Semaglutide also contains receptor inhibitors, that fill up the receptor active sites. We see that the small molecule phentermine can also fill this active site to block it, but it will dissociate with the receptor more rapidly.
Active GLP-1 protein secondary structure
Semaglutide will decrease blood sugar levels like other weight loss drugs, including phentermine. Semaglutide and phentermine are glucagon-like peptide-1 receptor agonists, decreasing the activity of the receptors. Both drugs elevate brain norepinephrine and dopamine levels. Semaglutide has been shown to increase the neurotransmitter GABA (gamma-aminobutyric acid) as well. On average, using semaglutide for a month will result in a 3-5% reduction of body weight.
Comparison with other weight loss drugs
Semaglutide, hormone-based drug, is most similar to other hormone-based drugs called liraglutide (marketed as Saxenda and Victoza) and tirzepatide (marketed as Zepbound, Zepbound KwikPen ). All of them contain a hormone signature; all of them work effectively to reduce body weight. Liraglutide was the first to be introduced (2009 in EU, 2010 in USA) in the drug market, followed by semaglutide (2017 in USA) and tirzepatide (2022 in USA). In contrast, small-molecule drugs such as phentermine (1959 in USA), bupropion (1985) and naltrexone
Orlistat was introduced into the marketplace in the UK in 1998
Naltrexone was first made in 1965 and was approved for medical use in the United States in 1984. It is a drug that is also used for smoking cessation.
View a list of weight loss drugs here: https://www.drugs.com/condition/obesity.html
Supplements and natural products
- Studies show that supplementation with amino acid L-histidine (4 grams per day) reduces body weight 2 pounds per month, with a significant reduction in waist circumference
- GABA supplementation alone has been shown to reduce body weight and waist circumference
- Neopuntia (isolated from cactus) and Guarana (derived from a vine plant) aid in weight reduction and are marketed in special coffee blends
- Peptides for muscle building
- isoleucine supplement weight loss pubmed
Lifestyles change always help maintain lower body weight
- Actively exercising five days a week for an extended period of time will likely reduce body weight and build a healthy muscle
- Optimizing eating habits; going vegan for instance.