Brief Summary
This podcast episode examines the potential side effects of GLP-1 weight-loss drugs like Ozempic and Zepbound, focusing on suicide risk, thyroid and pancreatic cancer, pancreatitis, and bowel obstruction. It balances the alarming warnings with the statistical rarity of some side effects and the potential overall health benefits of weight loss, including reduced cancer risk. The episode also touches on concerns about data suppression by drug companies and the challenges of accurately assessing long-term risks.
- GLP-1 drugs carry warnings for potential side effects like thyroid tumors, pancreatitis, kidney injury, and suicidal thoughts.
- Studies suggest GLP-1 drugs may lower the risk of suicidal ideation.
- GLP-1 drugs are associated with an increased risk of thyroid cancer, but the overall risk remains low.
- GLP-1 drugs may significantly increase the risk of pancreatitis and bowel obstruction, although these events are rare.
- Weight loss achieved through these drugs could potentially lower overall cancer risk and provide cardiovascular benefits.
Introduction to GLP-1 Weight-Loss Drugs and Their Potential Side Effects
The podcast introduces a series on Ozempic and other GLP-1 weight-loss drugs, addressing concerns about potential side effects such as suicide, pancreatitis, bowel obstruction, thyroid cancer, and pancreatic cancer. Regulatory authorities have expressed concerns about the potential risks of acute pancreatitis, thyroid cancer, and kidney failure, which are included as warnings in the drug packaging. The package inserts for Ozempic (semaglutide) and Zepbound (tirzepatide) list warnings and precautions, including thyroid tumors, acute pancreatitis, gallbladder disease, low blood sugar risk, kidney injury, allergic reactions, worsening eye disease, increased heart rate, and suicidal thoughts and behaviors.
Suicide Risk and GLP-1 Drugs
The possibility of adverse psychiatric events with GLP-1 drugs is biologically plausible due to the presence of GLP-1 receptors in the central nervous system. However, a meta-analysis of randomized controlled trials did not find any detrimental effect on mental health, including suicide risk. Newer studies with real-world subjects also showed no clear increased risk. One study found that semaglutide (Ozempic) was associated with a lower risk of suicidal ideation, potentially cutting suicidal thoughts by more than half compared to older weight-loss drugs. Weight reduction treatments can improve mood by reducing the burden of obesity.
Thyroid Cancer Risk and GLP-1 Drugs
Wegovy and Zepbound carry black box warnings for thyroid cancer risk due to dose-dependent thyroid tumors observed in rodents at clinically relevant exposures. It is currently unknown whether these drugs cause medullary thyroid carcinoma in humans. As a precaution, these drugs should not be prescribed to individuals with a personal or family history of thyroid cancer. Doctors should advise patients to watch for symptoms of thyroid tumors, such as lumps or swelling in the neck, trouble swallowing, shortness of breath, or persistent hoarseness. Research on GLP-1 drugs like Ozempic has shown an increased risk of all thyroid cancers, particularly medullary thyroid cancer, after a few years of use. A meta-analysis found a significant increase in the risk of overall thyroid cancer, with about 52 percent greater odds. However, the overall incidence of thyroid cancer in the population is low, with only about three people out of 1,000 expected to get the cancer over a decade. Even with a 50 percent increase in risk, only about four in 1,000 would get it over a decade. The five-year relative survival rate for thyroid cancer is 98.4 percent, indicating it is a relatively mild cancer.
Pancreatitis and Bowel Obstruction Risk with GLP-1 Drugs
The most common side effects of Ozempic-type weight-loss drugs are gastrointestinal issues like nausea, vomiting, diarrhea, and constipation. Ozempic may also increase the risk of pancreatitis, kidney failure, and thyroid cancer. Kidney issues may arise from dehydration due to vomiting or diarrhea caused by the drugs. GLP-1 drugs were associated with nine times more pancreatitis and a four times higher risk of bowel obstruction compared to older weight-loss drugs. GLP-1 slows down the digestive tract, which can lead to nausea but also promotes fullness and weight loss. In rare cases, it can cause the gut to become so sluggish that it stops working, leading to a blockage requiring surgery. The number needed to harm for bowel obstruction after one year of use is 1,223, meaning over 1,000 people would need to take the drug for a year to cause one extra case. The cumulative risk after 10 years of treatment is less than one percent. GLP-1 receptors are abundant in the pancreas, and GLP-1 therapy can cause the cells of the pancreas to proliferate, potentially leading to inflammation. Studies suggest GLP-1 drugs may increase the odds of pancreatitis as much as six-fold.
Pancreatic Cancer Risk and Concerns About Data Suppression
The major concern is subclinical, asymptomatic inflammation of the pancreas, which can predispose individuals to pancreatic cancer. Some rats showed potentially premalignant changes in their pancreases while on these drugs. The pro-proliferative actions of GLP-1 could accelerate the progression of premalignant lesions towards cancer. GLP-1 drugs are modeled after a compound found in Gila monster saliva, which the lizard uses to rapidly proliferate its tissues after long periods without food. A British Medical Journal investigation revealed unpublished data from animal and human studies indicating pathological changes in the pancreas, with drug companies allegedly suppressing scientific debate by withholding safety data. Companies may be incentivized to avoid monitoring the safety of their products to avoid legal liability, a concept referred to as the "three monkey paradigm." A professor at the Mayo Clinic suggested that most patients and clinicians might opt to avoid GLP-1 based drugs or limit their use to a short period. A study of transplant-quality pancreases from accident victims who had been taking GLP-1 drugs for at least a year showed abnormalities in every pancreas, including enlargement, dysplasia, and small tumors.
Current Understanding and the Broader Context of Cancer Risk
It remains unclear whether the use of GLP-1 drugs is linked to an increased risk of pancreatic cancer, and trials would need to be enormous to exclude such a risk. Most data may remain hidden from independent scrutiny. Thousands of pancreatic cancer cases have been reportedly tied to GLP-1 drugs via the FDA's Adverse Events Reporting System, but these databases are limited by potential reporting bias. If there is even a remote chance that certain drugs can impact cancer development and progression, such risks should not be taken lightly. Being overweight increases the risk of 18 different kinds of cancer. Weight loss achieved through these drugs could potentially lower overall cancer risk. A meta-analysis of bariatric surgery studies found that significant weight loss can lower the risk of getting and dying from cancer. Widespread use of new-generation weight-loss drugs like Ozempic could prevent more than 1 out of 100 cancers over the next 25 years. The cardiovascular benefits of significant weight loss may outweigh any potential risks.
