Ozempic: A Case Study in Hybris

We owe the pharmaceutical industry a great debt of gratitude as a society. There is no doubt that modern medicine has given us tremendous benefits. The list of luminary scientists who paved the way for modern medicine and the establishment of the pharmaceutical industry is long: in the 17th century, Nicholas Culpeper collated current medical knowledge on herbal remedies and the specific ailments they were useful for. A century later, William Withering discovered the medicinal properties of foxglove for treating heart conditions. Alexander Fleming, Paul Ehrlich and Gertrude Elion all received Nobel Prizes for their accomplishments. We live in an era where Novo Nordisk—the Danish pharma giant—has a market capitalisation that is larger than the GDP of Denmark.

With such success, the risk of hybris is hard to avoid. We have conquered polio and smallpox. Leprosy is treatable, as is HIV. Measles, famously nearly wiped out by the vaccine, and tuberculosis, both once feared, no longer pose a threat to those that have access to modern medicine.

The list is much longer, and of course includes insulin, as the first man‑made protein to treat a disease, and will certainly not end with CAR‑T, the much‑hailed cell therapy, first approved in 2017 for the treatment of relapsed or refractory acute lymphoblastic leukemia (ALL). Each and every one of these advances resulted in tremendous benefits for patients.

Where modern medicine is at its most effective is where there is a single and well‑defined target that is the cause of the disease. This was even formulated expressly by Robert Koch in 1890 for the connection between a microbe and a disease. For the time, these guidelines were well founded, sensible, and immensely influential. If you want to identify the causal agent of a disease, follow Koch’s postulates.

What about diseases where there is no single cause? What if many factors contribute to your ailment? What about synergy, multi‑causality, redundancy, positive or negative feedback systems? These aren’t just words—these are ways in which organisms are organised and what complex systems are built on. In such complex systems, finding the singular causal anything is a non‑starter. Metabolic disorders are a prime example, as are chronic inflammation—which can lead to coronary diseases—, allergies, or mental health disorders such as depression or anxiety.

Still, the approach of modern medicine is to find the causal target and hit it with a molecule. The drug. The hammer. That remains our most sophisticated approach. At least here in the West.

Such is the case with Ozempic, chemical name semaglutide. It is being sold as a weight‑loss wonder drug. Ozempic accounts for billions of dollars of annual revenue for Novo Nordisk, and is responsible for a large part of its sales growth.

The drug is what is called a “GLP‑1 receptor agonist”—which means it targets the GLP‑1 receptor. According to the European Medicines Agency’s website:

How does Ozempic work? The active substance in Ozempic, semaglutide, is a “GLP‑1 receptor agonist”. It acts in the same way as GLP‑1 (a hormone produced in the gut) by increasing the amount of insulin that the pancreas releases in response to food. This helps with the control of blood glucose levels.

So, in laymen’s terms, there is a signalling pathway that tells the body to control appetite, and semaglutide activates that signal. On the face of it this sounds reasonable. Tell the body: you’re good—stop eating. If you can “fake” that message—by adding more of it—your’re golden. The molecule semaglutide is that message.

Or is it?

The sensation of satiety is regulated by not just one molecule. That would be insane. Or, to be more scientific, it would be overly simplistic. There are several hormones—which are body‑internal signalling molecules—that influence the feeling of satiety. Leptin is one, ghrellin another. There are even “stretch receptors” in the stomach that sense how physically full we are. Sugars, amino acids, fatty acids all influence our feeling of fullness or hunger. So trying to regulate our feeling of hunger using only one single active substance isn’t going to cut it. All the other pathways are still active and will do their utmost to regulate your sense of hunger. This is not a trivial pathway for our bodies. We need food, every day and in good quantity.

Recently, a fellow Substack author posted an analysis of an investment bank stating that Ozempic could be bigger than the iPhone. I sincerely hope not. Hybris and wishful thinking are close bedfellows. If we want to really help people regulate their appetite and their weight, we need to be smarter than this. Interestingly, we already have good alternatives. Such as shown by a recent study looking at spinach extracts. It hits the exact same pathway as Ozempic (the GLP‑1 receptor), among several other ones. There is more than one active compound in spinach extract. Together, they regulate blood sugar and the sense of satiety much more naturally than semaglutide. Maybe Novo Nordisk should invest in farming Amaranthacea. Stephen Fry, and millions of others, might be grateful.