Do GLP-1’s slow natural GLP-1 Production

In this blog post I want to review an interesting article I just read regarding GLP-1 medications. The article was posted on BBC.com for those interested in reading it in it’s entirety.

One of the major (not the only major, just one of the major) issues with the new GLP-1 drugs (tirzepatide and semaglutide) used for weight loss is that once a patient stops using the drugs they almost always regain the weight lost. A study in 2021 showed that After 68 weeks of semaglutide injections, the average patient lost more than 15% of their body weight, but within 12 months of treatment ending, patients regained two thirds of their prior weight loss on average. On top of this, the weight regain happened much more rapidly than the weight loss. The question is “why?”.

Dr. Martin Whyte states in the article that the doses of GLP-1 provided by semaglutide and tirzepatide are far greater than the body would naturally expect to receive, he says, which may suppress the body's ability to secrete GLP-1 on its own. As a result, people's hunger may return even more voraciously when they cease their doses. So, basically, he hypothesizes that taking the GLP-1 medication makes it more difficult for your body to make it’s own, natural, GLP-1. GLP-1 regulates hunger naturally so not producing it can cause hunger to become out of control. He goes on to state, “What may be happening, and we don't know for sure, is that when you stop them, your body's left in a GLP-1 deficit which has a major impact on the satiety signal going to the brain.”

Again, this is an assumption made by Dr. Whyte. Unfortunately, before approving this medication, this mechanism was not confirmed. The mechanism does make sense, however, if we look at how other natural hormones produced by the body respond when we take synthetic versions. When women go through hormone replacement therapy or me start testosterone replacement therapy, the extra hormones the receive exogenously slow the natural production of hormones in the body.

If this is the case, then the only treatment for success is to treat with these medications for life. This point is underscored by another doctor quoted in the article. Dr. Domenica Rubino states that "I try to explain that these are chronic medications, but I think everybody secretly feels, 'Yeah, but you know what, I'm different, and once I hit my weight goal, I'll be ok.' But the reality is, the brain is quite powerful."

The warning here, in my estimation, is that if you are going to start these drugs to lose weight then you better be prepared to stay on them for the rest of your life. You also better fully understand the long term side effects and costs associated with taking them. I, along, with Dr. Rubino se a sever disconnect with this reality and the perception of people starting these medications for weight management. It is up to health care professionals to fully educate patients on these, and other issues, related to taking medications before recommending treatment.