Semaglutide: The Skinny on Obesity's New Foe
Besides RNA vaccines, semaglutide might be one of the most fascinating discovery yielded by the persistent research that took almost a decade. FDA finally approved it last year after long clinical trials and, for the first time, there is possibility to eliminate obesity! 1/n https://x.com/deedydas/status/1581473508856455169
Semaglutide was created literally by molecular engineering! In 1990s it became know that GLP-1 hormone was the responsible agent for controlling glycemic response. That includes a lot of things including feeling full, secretion of insulin and pancreatic cells that makes insulin.\
If you want to solve obesity, you need to make sure this hormone is in good shape. One can make this hormone artificially but it has very small half life in minutes. So, major research efforts underwent during past decades to extend half life of this molecule. \
Researchers worked at molecular level, analyzing the amino acid sequences to find compatible molecules that can attach to GLP-1 and protect it. This is like a game of chess. Proteins have shapes and slots to attach to other molecules and that’s how they switch things on/off. \
If you let fatty acid molecule to attach GLP-1 to protect it, then it loses it efficiency to do its job. So, the challenge is to find right molecule and sites of attachments such that it gets protected, half life improved while it still can do its main job. \
The first glimmer of success came around 2010 with invention of Liraglutide. But this new altered molecule still had much small half life requiring daily injections while it’s effectiveness got reduced significantly. This is why we probably didn’t see it in the news. \
Researchers kept at it to find right modification to GLP-1, altering amino acid sequence and trying out many possible fatty acid molecules and ultimately hitting the lottery. The semaglutide molecule was discovered in 2012 with limited scope of treatment of diabetes. \
By 2017, there were strong indications on it’s impact on obesity. In next 4 years, more clinical trials and versions followed. The latest one concluding in 2021 which shows whopping 15% weight reduction in a single year without much of a significant side effects! \
15% weight loss in single year is huge and is usually only possible by surgery for people dealing with genetic/chronic obesity. The fascinating part is that semaglutide is now approved for anyone with BMI>30 because of lack of serious side effects and extraordinary trial results.
Things are still not perfect as semaglutide still requires weekly injections but we are getting tantalizingly closer to erase out obesity from humanity. The interesting part for me is how AI can accelerate such molecular engineering and revolutionize this field. \
When I looked at how semaglutide was discovered, I saw the monumental manual efforts to interpret and modify a single molecule that took years. AI can shorten this and make far more effective in coming years. Here’s the paper on discovery of semaglutide: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474072/pdf/fendo-10-00155.pdf