back in 2021, we did an episode on semaglutide, the then-recently approved drug for weight loss that was originally approved for type 2 diabetes. Since that episode, another paper has come out on what happens to weight when the drug is discontinued, another on Mounjaro, a drug approved for type 2 diabetes. That's the topic of this week's Healthcare triage. 

Semaglutide works by mimicking the hormone GLP-1, a hormone released in response to food. When this hormone arrived on teh scene, several things happen, including more insulin production, an increase in the time it takes for food to leave the stomach, and decreased food intake. Mounjaro, on the other hand, mimics two proteins, GLP-1 and GIP. GIP is thought to enhance the effect that GLP-1 has on lowering both glucose and weight, so the idea here is that activation of both of these receptors leads to better outcomes for both diabetes and weight loss.

In our 2021 episode on semaglutide, we described the impressive clinical trial results that had just been published in the New England Journal of Medicine. It was a double-blind, placebo-controlled trial with nearly 2000 participants that did not have diabetes but did have a high body mass index. 
Both the placebo and control groups were followed for 68 weeks, which is a reasonably long time. Given weekly injections, people in the placebo group lost an average of almost 6 pounds, compared to the treatment group, who lost an average of 34 pounds, which is pretty impressive. Importantly, a big chunk of that weight loss occurred in the first 20 weeks, and remained lost through week 68, meaning the weight loss had staying power-- something we don't usually see with typical diet and exercise. 

As for Mounjaro, a 2022 paper detail the results of a double-blind, randomized, placebo-controlled trial that enrolled over 2500 people with a high body mass index who did not have diabetes. Participants were randomly assigned to received either placebo or one of the three doses of the drug over a period of 72 weeks. 
The mean weight loss in the placebo group was close to 6 pounds, compared to a mean weight loss of about 28 pounds for all the drug dose groups combined.

That's a little lower than what we saw in the semaglutide trial, but weight loss in pounds was very likely higher with the higher dose rather than averaged across all doses. When we compare percentage weight changes by dose, which is what the paper provides, the Mounjaro group actually did better. The mean change in weight in the group receiving the highest dose of Mounjaro was 20.9%, while the mean change in body weight for Semaglutide was just under 15%.  It isn't technically correct to directly compare the results of these trials given the differences in methods and study population, but there you have it. 

The looming question is whether these drugs would need to be taken forever, and the answer to that is: we don't know for sure yet. But data published from the semaglutide trial in mid-2022 suggests this might be the case. Looking at the period from week 68 to week 120, with the drug being taken away at week 68, we see that weight was regained fairly rapidly.

While the Mounjaro report mentions a 4-week safety follow up and an additional two years of treatment for participants with pre-diabetes, it's unclear if they will follow up and report on participants after the drug has been discontinued. 

Some people are uncomfortable with the idea of being on a drug forever, particularly a drug that has potential serious side effects, and for which the effects of continued use are uncertain. It's possible the drug could be taken intermittently, say, like, a few months on, a few months off, but it's hard to say until we've had more time to get more data. While the relationship between obesity and health is very complicated, and often misrepresented, weight is a definitive factor in some health problems, and weight loss is really, really hard. We certainly look forward to more data on some of the side effects and on the long-term implications of use, but for now, these kinds of results are a pretty big deal. 

Hey did you enjoy this episode? You might enjoy this other episode on how exercise is not the key to weight loss! We'd appreciate it if you'd Like this video, perhaps subscribe to the channel down below, and go on over to patreon.com/HealthcareTriage where you can help support the show, make it bigger and better. We'd especially like to thank our research associates, Joe Sevits, and Edward Liljeholm, and of course, our surgeon admiral Sam.