Weekend Reading | The science behind Ozempic, Wegovy and other GLP-1 agonists

by Kevin Schofield

This weekend’s reading is a post on Substack by Dr. Scott Alexander on the latest “wonder drugs”, Ozempic and Wegovy. Both began as diabetes treatments, but in the last year have gained notoriety as weight loss drugs. Recently, research has emerged that suggests they may be useful treatments, or preventative medications, for a number of other diseases: stroke, heart disease, kidney disease, Parkinson’s and Alzheimer’s, as well as a variety of different addictions. both substance and behavior).

It looks like someone is selling snake oil out of the back of their wagon. And yes, as Alexander points out, after a decade the list of diseases that Ozempic and Wegovy are good at treating will certainly have narrowed considerably. But at the same time, in this case, there is real evidence that the uses are broad, something that is very unusual—almost unheard of—in health care. So Alexander digs into the biochemistry of why, this time, it might be up to the hype.

Ozempic and Wegovy are in a class of drugs called “GLP-1 agonists,” a term that requires packaging. GLP-1 is a hormone, a molecule used by our internal organs to communicate with each other. In this case, the hormone GLP-1 is created naturally by our gut when it senses the presence of food, mainly as a signal to the pancreas. The pancreas is responsible for maintaining the proper level of glucose in our blood by releasing two other chemicals: insulin to remove glucose or glucagon to add more. When GLP-1 binds to receptors on pancreatic cells, the pancreas knows that digested food will turn into a fresh supply of glucose, so it increases insulin and decreases glucagon.

People with diabetes have difficulty regulating their insulin levels, often because their bodies do not properly generate GLP-1 when needed. Unfortunately, the GLP-1 hormone that is naturally generated by our bodies only lasts about two minutes, so we can’t just take it from one person and inject it into another. Instead, the researchers invented new molecules called “GLP-1 agonists” that mimic GLP-1 well enough to activate the same receptors in the pancreas, but last much longer—up to a month. By reactivating our body’s ability to control insulin and glucagon levels, these drugs are effective treatments for some forms of diabetes.

Where this story gets interesting is the discovery that there are several other types of cells, spread throughout our body, that also have GLP-1 receptors – so when the gut starts sending out GLP-1, they are also triggered. Some of them are in the part of our brain that recognizes when we are full, that is, when we have eaten enough. In retrospect, this should come as no surprise; if there is food in our digestive system, we should stop eating. But this is the crux of why these drugs are now used for weight loss: they tell our brains that we don’t need to eat.

It turns out that there are also cells with GLP-1 receptors in the “reward center” of our brain: the part associated with cravings and addictions. It should also come as no surprise to learn that the brain’s reward center talks to our gut, as we all have food cravings and the connection to the digestive system is an effective way for our bodies to prioritize food (including types of special food). when it feels like it’s lacking some important nutrients. Or the opposite: The body can use GLP-1 as a signal to the brain to stop craving more food when it has eaten enough. But this is the same reward center that is implicated in a wide range of other addictions, both to substances such as alcohol, opioids and stimulants, and to behaviors such as pornography and gambling addictions. And this is probably why GLP-1 agonists can be useful to treat addiction. Researchers are still early in their investigation of this connection, but some are very excited by the possibilities of new treatments.

And this takes us even further, to Parkinson’s and Alzheimer’s diseases and other forms of dementia. Alexander explains that this is still not well understood, but we do know that one of the features these diseases share is that they involve cell damage. For example, it is well known that diabetes increases the risk of Parkinson’s and Alzheimer’s, most likely because high blood glucose levels can damage the cells in our body. But Alexander also notes that GLP-1 agonists seem to help with these diseases even in people who don’t have diabetes, so something else must be going on, too. He suggests that the most likely link is that GLP-1 agonists help reduce inflammation. Inflammation is part of our immune system’s response to foreign invaders, creating an environment that is mildly toxic to our cells but highly toxic to the invaders. But long-term chronic inflammation can cause enough damage to our bodies to lead to Parkinson’s, Alzheimer’s, other forms of dementia, and other “auto-immune” diseases like MS. Unfortunately, the modern Western diet, high in fat and sugar, can often lead to chronic inflammation and ultimately contribute to these diseases. But to the extent that Ozempic, Wegovy and other GLP-1 agonists keep inflammation at bay, they may prove to be effective preventative measures — or treatments.

It’s important to remember that much of this is still speculative, and some of it will eventually turn out not to be true. And we’ve been down this road before with treatments that doctors believe may have far-reaching health effects: the hormones in birth control pills (researchers are still trying to fully understand their effects), aspirin, serotonin, testosterone, and other treatments that naturally mimic substances found in our bodies. But it’s also true that GLP-1 agonists won’t be the last of these we discover; there is much we still don’t know about the conversations between parts of the human body, and where a change in one part will permeate many others.

Read Substack’s full post “Why Ozempic Cure All Diseases?” online.

Kevin Schofield is a freelance writer and publisher Seattle Paper Trail. Previously he worked for Microsoft, published Seattle City Council Insightco-hosted “Seattle News, Views and Brews” podcastand raised two daughters as a single father. He serves on the Board of Directors of the Woodland Park Zoo, where he also volunteers.

📸 Featured image: Ozempic semaglutide pen and injection box, November 16, 2023. (Photo: Marc Bruxelle/Shutterstock.com)