Welcome to Talk on Health. I’m your host Dr. Chet Zelasko. Talk on Health is a joint production with WGVU in Grand Rapids MI. I examine the practical application of health information. Nutrition. Exercise. Diet. Supplementation. I look at the science behind them, and let you know whether it’s something to consider or not. You can check out other things that I do on my website Drchet.com and sign up for my free emails.
We’ve seen what’s been going on with celebrities and neighbors alike. People that were once heavy have lost weight, sometimes a lot of weight, when they never were able to lose weight before. Everyone who’s succeeding now when failing so many times before, have no problem talking about what helped them do: GLP-1 receptor agonists. On this track, I’ll take you through how these medications work for T2D and weight loss as well as the side effects attributed to them.
Let’s start at the beginning. What exactly is Glucagon-like Peptide 1 AKA GLP-1? GLP-1 is a hormone released by the intestines while you eat. It specifically responds to blood glucose levels. How it’s produced is complex but suffice it to say that GLP-1 has an impact on insulin production, although as we’ll see later, it has far reaching effects.
How does the hormone do what it does? It enhances insulin production—which gets sugar out of the bloodstream—and reduces the release of glucagon—which increases the amount of sugar in the bloodstream from glycogen stores. The net effect of that delays the stomach from emptying quickly with the objective of reducing the amount of food eaten. In other words, it suppresses the appetite.
What else can GLP-1 do? The list is long but I think you’ll get a better understanding of how important it is if I list and explain them. Let’s start with the digestive system where the final processing of GLP-1 happens. As I mentioned earlier, the release of food from the stomach, technically called gastric emptying, slows down. In addition, the rhythmic nature of the small and large intestine also slows down. The net effect is you should feel full and stop eating.
In the liver, glucose production slows down because the pancreas has gotten the signal to increase the production of insulin while simultaneously decreasing the production of glucagon. Combining these two effects, there is no reason to make sugar from proteins or release it from glycogen stores if you’re getting a fresh supply as your food digests. Fat cells stop making fat cells and the fat mass starts to decrease.
Here's where it gets interesting. In the CV system, more glucose is used as fuel while lipid metabolism decreases. The actual functioning of the heart improves, providing cardiac protection. On top of that, inflammation decreases which is also cardioprotective.
The brain also seems to benefit from GLP-1. Normal food intake decreases as well as hedonic eating decreases. What’s hedonic eating? Eating for pleasure, taste, or emotional comfort, rather than to satisfy hunger or energy needs. Body weight decreases and the hormone exerts a neuroprotective effect.. Finally, at least for now, skeletal muscle can take up more glucose which can result in better workouts while exercising. To say that this hormone is important, is an understatement.
The success or failure of GLP-1H depends on the number of GLP-1 Receptors or the functional ability of the hormone to bind to the GLP-1 receptor. The number of receptors have been shown to be reduced during insulin resistance and T2D. Why does this happen? My suspicion is that chronic overeating down-regulates the genes that are responsible for making the receptors. Fewer receptors means that the hormone will not suppress appetite. Or the receptors become disabled in some way, again in response to overeating. The net effect is that we don’t get hormonal cues to stop eating and thus, less insulin is released and over time, blood sugar rises. We ignore natural cues that we’re full and continue eating. Not only can that impact blood sugar but also means the extra calories can be stared as fat.
What does a receptor agonist do? GLP-1 agonists bind to GLP-1 receptors and begins to do the things the GLP-1 hormone does. It stimulates the production of insulin in the pancreas that results in suppressing appetite and all the benefits I just got done talking about. Ignoring those signals results in some of the side effects people who use it may get.
I’m going to cover the most common side effects because the severe ones rarely happen. The common side effects begin with nausea and vomiting. When you begin taking the GLP-1 agonist, you may make the mistake of eating your previous volume of food. With stomach emptying slowed down as well slower peristalsis, the backing up of digesting food can cause those side effects.
Some people experience other digestive issues such as acid reflux, belching, gas, bloating and stomach pain or discomfort. I would expect that those side effects may improve over time as a person starts eating a more reasonable quantity of food. Then, there may be bouts of diarrhea and constipation depending on the types of food eaten. Remember, the agonist is not really working in the digestive system unless there are GLP-1 receptors in the digestive track or the agonist is difficult to break down for elimination.
Other side effects are fatigue, headache, and even hair loss. That may be due to a decreased appetite, which is supposed to happen, but may be more due to poor food choices. Just because you are forced to eat less doesn’t mean you’re eating the right foods. Finally, there may be changes to your face, a sort of sunken, look. The fat pads between bones and tendons often shrink if you lose weight too fast. That might be a characteristic of GLP-1 agonists as well.
There’s the story of GLP-1 the hormone, the receptor and the receptor agonist. The next question is what do I think about using it for weight loss. The agonists were originally developed to help lower HbA1c levels in pre-diabetics and T2D. The agonists do work. But because it has now been approved for weight loss, more and more people want to try it. My only question is What is your exit strategy? I’ve talked forever about eating less, eating better, and moving more to lose weight and maintain it and that’s what you have to do for the rest of your life.
If one of these agonists helps you to get there, it does so by forcing you to eat less. It doesn’t impact your metabolic rate nor pass calories through your digestive system without absorbing them. You have to eat less. If you take the opportunity to track what you eat, make healthier food choices, and move more while you do that, you’ll be in a position to maintain that weight loss. It will give you an edge. If you’re not going to do that work to be ready for when you ultimately go off the agonist, you will regain the weight you lost. That’s the final side effect that people cite when using agonists: regaining weight.
But that won’t happen if you take the opportunity to learn how to eat better, eat enough but no more, and keep moving. It all depends on whether you look at it as an opportunity to change your body for good or as another thing that didn’t work. It works if you will.
That’s it for this episode. If you like this podcast, please hit the like button and tell your friends and colleagues about it. Until next time, this is Dr. Chet Zelasko saying health is a choice. Choose wisely today and every day.
References :https://www.biochempeg.com/article/299.html
NIH Books Stat Pearls NBK551568
Prog Mol Biol Transl Sci. 2014 ; 121: 23–65.
