The Key to Long Term Weight Loss

What Ozempic/ Wegovy/ Mounjaro teaches us about Weight Loss

It’s about Controlling Hunger, not Calories

Dr. Jason Fung
10 min readNov 16, 2023

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The GLP-1 Agonist Class of Drugs

Semaglutide (trade named Wegovy and Ozempic), is part of the drug class GLP1 (Glucagon Like Peptide 1) agonist. This is not a new drug class, as it has been around since the discovery of exenatide (trade name Byetta) in the venom from the saliva of the Gila monster.

It was first approved for use in the United States in 2005. The GLP1 hormones are part of the hormone class called incretins, with many different physiologic effects. They are secreted mainly in the stomach and the main effect was thought to increase insulin secretion from the pancreatic beta cell in response to glucose given by mouth (but not by intravenous since it bypasses the stomach).

The very cute Gila Monster

The enhanced insulin secretion was useful to reduce blood glucose in type 2 diabetes. Exenatide saw only modest success because it was inconvenient. It needed to be injected twice daily. It caused mild weight loss, at best 2.5 kg weight loss (5.5 pounds). Yes, you lost weight, but it was nothing to write home about.

Next came liraglutide (trade name Victoza), developed as a easier to use version of exenatide because it could be taken once a day instead of twice. It also produced weight loss — about 4–6 kg (8–13 pounds). Not bad, but not amazing either.

Then along came semaglutide (Ozempic or Wegovy), developed essentially as an updated version of liraglutide. Instead of daily injections, it would be weekly injections. The easier to use, the more likely people will use it. And it worked. But people soon noticed something else. People weren’t losing a little bit of weight — they were losing a LOT of weight.

STEP 1 Trial — Weight Loss with Semaglutide

In the STEP 1 trial, published in the New England Journal of Medicine, people taking semaglutide lost about 15% of their original body weight. A 200 pound person…

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Dr. Jason Fung

Nephrologist. New York Times best selling author. Interest in type 2 diabetes reversal and intermittent fasting. Founder www.TheFastingMethod.com.