Do GLP-1 Drugs Like Ozempic (Semaglutide) Cause Pancreatitis and Pancreatic Cancer?

"Do GLP-1 Drugs Like Ozempic (Semaglutide) Cause Pancreatitis and Pancreatic Cancer?" The most common adverse side effects of Ozempic-type weight-loss drugs are gastrointestinal issues, including nausea, vomiting, diarrhea, and constipation, which I talked about in a previous video, as well as excessive lean muscle loss and gallbladder issues, discussed in a subsequent video, but Ozempic may also heighten the risk of pancreatitis, kidney failure, and thyroid cancer. I talked about the thyroid cancer risk in my last video. Many of the kidney issues may stem from dehydration due to excessive vomiting or diarrhea caused by the drugs, but what about the pancreas inflammation? Analyzing the prescription records of 16 million Americans, compared to taking an older class of weight-loss drugs, the use of GLP-1 drugs like Ozempic was associated with nine times more pancreatitis, as well as four times higher risk of bowel obstruction. Remember, GLP-1 slows down your digestive tract. That’s part of the reason people get nauseous and barfy, but that’s also part of why you feel fuller for longer and lose weight. But sometimes, it can make your gut so sluggish, it stops working, and you get a blockage that could become a surgical emergency. It’s super rare, though. The number needed to harm after one year of use is 1,223, meaning that more than 1,000 people would have to take the drug for a year to cause a single extra case of bowel obstruction. So, even after 10 years of treatment, your cumulative risk would be less than one percent. But what about this 800 percent increased risk of pancreatitis? Digestive hormones like GLP-1 act on multiple targets within the body, with multiple effects, perhaps more "magic shotgun" than "magic bullet," but maybe not so magical for the pancreas. GLP-1 receptors are expressed abundantly throughout the pancreas, and in response to GLP-1 therapy, the cells of the pancreas proliferate, swelling the organ and potentially squeezing off ducts, causing inflammation, at least in rats, but that led to human studies like this, suggesting that GLP-1 drugs may increase the odds of pancreatitis as much as six-fold. This led some investigators to conclude that the balance of evidence suggests an association between the use of GLP-1 based therapies and acute pancreatitis. The major concern is not pancreatitis, though. Acute pancreatitis is unpleasant enough, but the major concern is subclinical, asymptomatic inflammation of the pancreas, because inflammation of the pancreas is well known to predispose to pancreatic cancer, which is one of the deadliest forms of cancer. And some of the rats did show potentially premalignant changes in their pancreases on these drugs. The concern is that the pro-proliferative actions of GLP-1 could take premalignant lesions and accelerate their progression towards cancer. Remember how these drugs were modeled off a compound found in Gila monster saliva? Few have paused to wonder why they would produce it. The answer is that the Gila monster is a desert lizard that goes for weeks or even months between meals and conserves energy during those intervals by shrinking its digestive tract, including its pancreas. So, when it finally does eat, it needs a way to rapidly proliferate its tissues. After reviewing thousands of pages of documents obtained through freedom of information requests, a British Medical Journal investigation unearthed unpublished data from animal and human studies that point to pathological changes in the pancreas, including attempts by drug companies to suppress scientific debate by withholding important safety data from the public. Why have the companies been so slow to respond to this threat? Because of the "three monkey paradigm," which operates as follows. Companies are legally responsible for monitoring the safety of their own products, but obviously can’t be held responsible for tackling a safety concern that does not exist. A concern that can be plausibly doubted or denied carries no legal liability, whereas one that gives rise to serious consideration leaves the door wide open to lawsuits. Thus, inviting companies to monitor the safety of their own products provides them with the strongest possible incentive for failing to do so, an instance of the law of unintended consequences. The three monkeys, who neither hear nor see nor speak, have been allowed to flourish at the heart of our system for protecting the public. "After careful reflection," wrote a professor of medicine at the Mayo Clinic, "most patients and clinicians may opt to avoid GLP-1 based drugs or at least avoid using them for a prolonged period of time." And this was all before this pivotal study came out, where researchers obtained transplant-quality pancreases from, like, accident victims who had been taking GLP-1 drugs for at least a year before they died, and every single pancreas showed abnormalities, marked enlargement, dysplasia, and even a few little tumors. This was all discovered more than a decade ago, though. Where are we now? It remains unclear whether the use of GLP-1 drugs is linked to an increased risk of pancreatic cancer. But trials would have to be enormous to exclude an increased risk, and unless the rules change radically by the time they are to be reported, most of the data will remain hidden from independent scrutiny. And as one Johns Hopkins drug safety researcher asked, "The fundamental question is who bears the burden of the passage of time while these debates are settled?" Thousands of pancreatic cancer cases have been reportedly tied to GLP-1 drugs, like Ozempic, based on the U.S. Food and Drug Administration’s Adverse Events Reporting System, but adverse event databases that rely on voluntary reporting are limited by the potential for reporting bias. That’s like the Centers for Disease Control’s VAERS database, the Vaccine Adverse Events Reporting System. During COVID, the more states were inclined to vote Republican, the more likely their vaccine recipients or clinicians were to report COVID vaccine side effects; so, maybe there was some kind of similar reporting bias among those who submit their pancreatic cancer to the FDA? Either way, if there is even a remote chance that certain drugs can have an impact on cancer development and progression, then such risks should not be taken lightly. But if you really don’t want to get cancer, then you really don’t want to be overweight. Based on a study following millions of people, the longer you’re overweight or obese, the higher your apparent risk of 18 different kinds of cancer. So, even if you cared only about cancer, might these drugs actually lower your overall cancer risk if they caused enough weight loss? A meta-analysis of bariatric surgery studies found that those going under the knife tend to lose so much weight that they have a significantly lower risk of getting cancer and appear to cut their risk of dying from cancer nearly in half. This modeling study suggests that widespread usage of these new-generation weight-loss drugs, like Ozempic, could prevent more than, like, 1 out of 100 cancers over the next 25 years. And that’s just cancer. Wouldn’t just the cardiovascular benefits of losing a lot of weight alone outweigh any potential risks? That’s the subject of my next video: Do the benefits outweigh the risks?