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 (C18) molecule linked to a peptide produced by the digestive and nervous systems, glucagon-like peptide-1 (GLP-1). The GLP-1 is made up of 37 amino acids, and this sequence is slightly modified to make the drug semaglutide. The crystal structures of either peptide show the peptides have alpha-helical tertiary structure. The semaglutide peptide contains 2-aminoisobutyric acid, which is similar in structure to another prescribed weight loss drug, phentermine. All modifications of the GLP-1 hormone to make semaglutide peptide are as follows: the first six amino acids are deleted, Alanine 8 is replaced with aminobutyric acid (mentioned above), Lysine 26 is attached to a C18 fatty acid, Lysine 34 is replaced with Arginine, and an extra amino acid, Glycine is added to the end of semaglutide..
Comparison with similar weight loss drugs
Semaglutide, a peptide-based drug, is most similar to other peptide-based drugs called liraglutide (derived from human GLP-1 hormone; marketed as Saxenda and Victoza), retatrutide (derived from GLP-1 as well as human Gastric inhibitory polypeptide, GIP and glucagon receptor, GL-R), and tirzepatide (derived from GLP-1 as well as GIP; marketed as Zepbound, Zepbound KwikPen ). All of them contain a hormone signature(s); all of them work effectively to reduce body weight. Liraglutide was the first peptide-based weight loss drug to be introduced (2009 in EU, 2010 in USA) in the drug market, followed by semaglutide (2017 in USA), tirzepatide (2022 in USA) and retatrutide (2026 in USA).Semaglutide, as well as the other hormone-based medications work effectively for weight loss, with an average reduction of 3-5% body weight within the first month.
Comparison with small-molecule drugs
In contrast, small-molecule drugs such as phentermine (1959 in USA), bupropion (marketed as Wellbutrin, 1985), naltrexone (1984) and orlistat (1998) were introduced into the market much earlier. Topiramate (marketed as Qsymia) was originally an epilepsy treatment with side effects including weight loss; and was therefore repurposed for weight management (used in combination with phentermine) starting in 2012. Buprenorphine is a drug used for opioid addiction or pain management with a common side effect of weight loss. Topiramate, bupropion, phentermine and buprenorphine all contain quaternary Carbons in their structures, making structurally similar to the isobutyl modified alanine in semaglutide.
Vitamins and metabolites with similar structure
Multiple key vitamins and metabolites have quaternary carbons and are similar in structure to the isobutyric acid in semaglutide and weight loss drugs. Vitamin B5 (pantothenic acid), pantethine and acetyl-CoA are involved in metabolism of fats and carbohydrates. If a drug looks similar to vitamins and metabolites, then it is likely that they interfere with these metabolite pathways. Vitamin B5, pantethine and coenzyme A (CoA) are involved in fat metabolism, energy production, and cholesterol regulation. These systems are targeted with weight loss drugs.
Supplements for weight loss
- Carotenoids - beta-carotene, zeaxanthin and lutein research indicates that supplementation alone assists in reductions in body weight and fat mass
- Plant sterols - Studies show plant sterols supplementation decreases weight gain by inhibiting absorption of cholesterol in the gut
- 2-aminoisobutyric acid, has a quaternary Carbon motif found in antibiotics and weight loss drugs and supplements
- Ipamorelin is a body building peptide (amino acid sequence: A(ib)HXFK) that helps with fat loss and muscle gain. Similar to semaglutide due to modification of alanine to include a quaternary Carbon