Q&A: Why Do I Feel Fatigued on GLP-1s?

Q: What Causes Nausea and Sulfur Burps on GLP-1s?

A: GI side effects are the biggest complaint in all of these GLP-1 medications. In some trials, the dropout rate is up to 17%.

But we can treat it, and everyone I start this on can tolerate it because we have a protocol that helps relieve and prevent any of these side effects!

What’s happening with sulfur burps is that there’s actually too much food sitting in the stomach. It’s your body’s way of saying, “I can’t digest this, I can’t take any more food right now.” And it’s because these meds do slow down digestion. My anesthesiology colleagues have found that they want people stopping Mounjaro a full 10 days before any planned surgery, as opposed to just telling them to fast before midnight. It’s a very powerful med!

To help, you can focus on foods that don’t take up too much space in the stomach and that are easy to digest. A lot of people will be surprised at this, but vegetables can actually take up a lot of room in the stomach and are harder for the body to break down, so I recommend a focus on protein. Also, you can wait to drink water or liquid until after eating to take up less space in the stomach.

For nausea, I recommend keeping electrolytes by your bed to drink first thing in the morning, which can help with fatigue and nausea. Nausea can be the body asking for salt!

I also recommend a B Complex for people on GLP-1 medications.

A B-complex will really help cut down on nausea and can generally have a nice effect on cutting down on a lot of these GI side effects.

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Q: Why do people feel fatigued on GLP-1s?

A: Since GLP-1s reduce blood sugar, even a few point reduction is enough for the body to be like, ‘what’s going on?’ Generally speaking, the fatigue goes away by the end of the first month, and then it hits you again when you go off on the dose. And so what I really remind people is that this is normal. And this is a journey that we’re on, and once we get you to your maintenance dose, this will go away.

Dehydration can also play a role in this. Electrolytes are very much your friend! Sodium and salt bring the water you drink to the right places in your body. So even if you’re chugging the water, if you don’t have salts along with it, you will not get it into the right parts of your body, and you’ll feel the effects.

And then the third thing that happens is that when the body is in a weight loss state, it’s recognizing that something’s happening, and it’s trying to figure out if it should be conserving energy to put up a fight. So people can feel some insomnia and also a bit of fight or flight mode, like “should I be alert in the middle of the night?”

So, I really remind people that we can’t stress out our bodies too much. Over time, our bodies adapt to a new state. But that’s why we taper up on these medications gradually and do expect at least a little bit of fatigue during the process.

Q: What’s the Science Behind Metabolic Dysfunction?

A: So a lot of people come to me and say, ‘I am trying so hard, and the weight stop coming on. And I know you won’t believe me.’ And I’m like, ‘Of course I believe you. This is all I do.’ 

In my opinion, fat is the most powerful organ, and metabolic dysfunction is really what happens to lead to excess fat. It could be an endocrine disorder, where we have decreased leptin, which is the satiety hormone, and a lack of reserve in the brain and stomach for stopping. Or it could be insulin resistance. We have all sorts of imbalances that will lead to weight gain. And then, when you put on the weight, there are negative feedback signals, and that further dysregulates what’s going on. 

As insulin resistance or metabolic syndrome grows, it gets really impossible for the body to become efficient at burning whatever food you’re bringing in, and your body just goes into a fat storage mode.

I include metabolic dysfunction as insulin resistance, even early insulin resistance. For someone to meet the criteria for true metabolic syndrome, they’ll show signs of elevated blood sugar, low HDL (good cholesterol), high triglycerides, and increased abdominal circumference.

When we can help people identify some of that dysfunction early on, in those early stages of weight coming on and not understanding, I really think we can stop a lot of disease in its tracks.

Q: Why Do Doctors Miss It?

A: I long recognized that there was a problem that people would come to me and say, ‘I ran all the labs and everything looks fine.’ And then I looked at the same set of labs and I would be like but no, you have early insulin resistance. And that’s just a runaway train. For most people, insulin resistance will progress to type two diabetes so we want to catch that.

Testing Fasting Insulin.

Testing fasting insulin is a very useful, scientifically validated tool that’s not used in clinical medicine, which allows us to predict pre-diabetes or insulin resistance 15 years before we see an increase in the average blood sugar marker.

I developed a kit, The Weight Biology Kit, that tests for fasting insulin in addition to the other markers that make up metabolic syndrome.

Shop the Weight Biology Kit

Q: How is Diet Culture Damaging to the Metabolism?

A: If you look at the Biggest Loser studies, you see excessive dieting and exercise, which initially leads to weight loss, but what does excessive calorie restriction ultimately do? It tanks your basal metabolic rate and puts you at a disadvantage unless you’re keeping up with that intense level of what it is you did to get there. Otherwise, you’re going to regain. With your basal metabolic rate lower, the weight comes back in waves.

Because of this, some people say, “Well, don’t lose weight at all.” But no, it’s just the extreme yo-yo that’s harmful, and losing weight needs to be done appropriately. The way we titrate medications like Wegovy helps people do it appropriately, where they’re losing between .5% and 1% of total body weight a week. It shouldn’t be more than that. 

Overall, we need to focus on macronutrients like protein and some sort of exercise. Strength training is best because it helps keep up basal metabolic rate.