You have probably heard many celebrities raving about Ozempic and other GLP-1 agonists for weight loss. But are these “miracle drugs” really a safe shortcut to good health?
In this article, I dive deep into the world of GLP-1 agonists, exploring their benefits and potential long-term health risks you need to know.
On an episode of the Joe Rogan Experience in June 2024, German entrepreneur and investor Christian Angermeyer referred to his use of a GLP-1 agonist as “outsourced discipline.” I thought that was an intriguing description for this type of drug, the most famous of which might be Ozempic. But what exactly did he mean by “outsourced discipline”? Let’s delve into that.
By now, most people are familiar with the GLP-1 agonist class of drugs. Names like Mounjaro (tirzepatide) or Ozempic (semaglutide) have made headlines everywhere. They have also become all the rage on social media, with many high-profile people admitting to using them, mostly in the context of weight management. As it turns out, one of the main effects of these drugs is appetite suppression, which explains Angermeyer’s interesting description.
GLP-1 agonists are peptides that were initially approved for treating type 2 diabetes. These drugs have been on the market as a diabetes treatment for two decades, a fact that might surprise many. However, researchers quickly noticed their impact on body weight. It is for this reason that ten years after their initial approval for diabetes, the first GLP-1 agonist, Saxenda (liraglutide), was cleared by the FDA for weight management in 2014.
But are these drugs safe? The short answer is yes. To gain regulatory approval, drugs must undergo clinical trials and meet specific safety and efficacy standards in humans. However, this doesn’t mean that long-term safety is fully understood by the time a drug hits the market.
Since their approval, several recent studies have raised concerns about the potential long-term effects of these drugs on certain health outcomes:
A reduction in lean body mass, including bone density, unless combined with other weight management interventions such as exercise.
A recent animal study showed that semaglutide (Ozempic) reduced the size of heart muscle cells in mice.
A study using the world’s largest database of drug safety reports (the WHO’s ICSRs database) found that suicidal thoughts were reported more often with the medication semaglutide compared to other drugs.
It’s important to note that some of these studies are not randomized clinical trials (RCT) and therefore, we do not yet know whether there is a causal relationship in humans.
For example, regarding the study investigating the association between semaglutide and suicidality, further research is needed to elucidate this relationship. The higher prevalence of depression among individuals with obesity makes this relationship hard to parse, and adjusting for “collider bias” with this type of data is particularly challenging. However, the emergence of cases of depression and suicidality, even when clinical trials for these drugs exclude patients with these conditions, is concerning.
Additionally, this is not an isolated report. Last year, another JAMA publication raised similar concerns (see also Verovnik & Vovk, 2023).
Despite these health concerns, these drugs have become a boon for the pharmaceutical companies that developed them. Take, for instance, Novo Nordisk, the Danish drugmaker behind Ozempic and Wegovy. In 2024, it reached a market value past $500 billion, making it Europe’s biggest company by market capitalization.
Whether GLP-1 agonists are miracle drugs or a ticking time bomb remains to be seen. Shortcuts to good health—especially pharmaceutical ones—are fraught with risks. As more data emerge, it appears that without accompanying lifestyle changes, these drugs could lead to serious adverse effects. “Outsourced discipline” might be tempting, but in biology, there’s no substitute for actual discipline.
**DISCLAIMER**
Consult a medical doctor before starting, changing, or stopping a medication for any condition. This information is NOT intended to provide medical, professional, or licensed advice and is not a substitute for consultation with a healthcare professional.
References
Schoretsanitis G, Weiler S, Barbui C, Raschi E, Gastaldon C. Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality. JAMA Netw Open. 2024;7(8):e2423385. Published 2024 Aug 1. doi:10.1001/jamanetworkopen.2024.23385
Jensen SBK, Sørensen V, Sandsdal RM, et al. Bone Health After Exercise Alone, GLP-1 Receptor Agonist Treatment, or Combination Treatment: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024;7(6):e2416775. Published 2024 Jun 3. doi:10.1001/jamanetworkopen.2024.16775
Martens MD, Abuetabh Y, Schmidt MA, et al. Semaglutide Reduces Cardiomyocyte Size and Cardiac Mass in Lean and Obese Mice. JACC: Basic to Translational Science, 2024. doi.org/10.1016/j.jacbts.2024.07.006.
Ruder K. As Semaglutide's Popularity Soars, Rare but Serious Adverse Effects Are Emerging. JAMA. 2023;330(22):2140-2142. doi:10.1001/jama.2023.16620
Verovnik B, Vovk A. Semaglutide, suicidal ideation and behaviour: A resting state functional magnetic resonance imaging perspective. Diabetes Obes Metab. 2024;26(2):782-784. doi:10.1111/dom.15363