Compounded Semaglutide
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This week we talk about Wegovy, Eli Lilly, and HIMS. We also discuss pig pancreases, beneficial side-effects, and shortages. Recommended Book: The Death Café Movement by Jack Fong Transcript In the 1970s, a pair of researchers looking into possible ways to address duodenal ulcer disease were studying the way we secrete different hormones while eating, and that led to an experiment in which they pumped a hormone called glucagon-like peptide 1, or GLP-1, extracted from pigs, into pig pancreases to see what effect that would have. As it turned out, this hormone stimulated the secretion of insulin while inhibiting the secretion of glucagon, and that was notable to these researchers because folks with diabetes have too much glucagon in their bodies, which is what causes high blood sugar. The idea, then, was that by stoking the production of more insulin and limiting the amount of glucagon being produced, you might be able to help folks with type 2 diabetes control their symptoms. These researchers shopped around the idea of building a treatment based on this hormone a little bit in subsequent years, but didn’t get much interest from the major drug companies. In 1993, though, they were able to do a study that showed that infusing folks who have type 2 diabetes with GLP-1, they could reset their blood glucose levels back to normal within just four hours, which was a pretty big deal—a lot better than most other options at the time. A drug based on this hormone was approved by the FDA for medical use in the US in 2017 under the name Semaglutide, and by 2021 it had become one of the top 100 most-prescribed drugs in the country—which is saying something, as the US is awash in pharmaceutical options, these days. Even before that approval, though, there were signs that GLP-1 receptor agonists, which is what Semaglutide and other drugs based on this concept are called, might have also had some other uses. In some of the clinical trials in which they were trying to gauge how well folks with type 2 diabetes faired while using the drug, for instance, they found that many of their subjects had trouble finishing the meals they were supposed to eat, which was a problem, as having that meal was part of the process, and after they ate it, ideally the whole thing, researchers would measure their blood insulin—so keeping that controlled was kind of important for their results, but the subjects consistently just weren’t as hungry as they typically would have been. Interestingly, this realization led to a proposal by one of those original researchers to the drug company Novo Nordisk, the company that brought Semaglutide to market, for another drug that would help people control their appetite and consequently limit food intake, perhaps serving as a means of remediating obesity, which at the time, in 1998, was already becoming a big health issue of significant global concern and widespread impact. The company didn’t end up doing anything with the patent they went in on with that researcher, but they did pursue something along those lines a little bit later, which approached the issue with a similar underlying substance, but via a different route. And in March of 2021, the company started clinical trials for that drug, which eventually became Wegovy, using basically the same substance as Semaglutide, but in a different volume, and the adult subjects in that trial lost a significant amount of weight. A few months later, in June of 2021, Wegovy was approved for use in the US to treat adults with obesity, and then in December the following year it was approved for use by obese teens, as well. Now, Wegovy and its effects were in some ways forecasted in those trials for Semaglutide when test subjects were eating less than usual while on the drug, and something similar happened here, as subjects who were being given Wegovy for weight loss purposes were showing other, unanticipated positive effects, as well. Among those effects were positive car
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