Do GLP-1s The Right Way—You Shouldn't Feel Exhausted, Nauseous, or Unable to Workout

Did a podcast this morning and it reminded me about something important—there are so many new people in this space, especially those of you starting tirzepatide or retatrutide, who might be making critical mistakes without even realizing it.

Let me share some context. I was lucky enough to get into tirzepatide NOT wanting to lose 70 lbs—I did that part before. I started tirzepatide to calm that overall food noise and stay at maintenance. I'm also the type of person who will do months of research and figure out everything about a peptide before I dive in.

As part of that research, I already understood proper dieting and the dangers of putting yourself into too harsh of a deficit. So let me break this down for you:

If you're feeling tired, nauseous, and can't eat—your dose is too high.

Here's what's actually happening in your body when you push the dose too hard:

GLP-1 agonists like tirzepatide work by slowing gastric emptying (how fast food leaves your stomach) and signaling satiety centers in your brain. When you dose too aggressively, you're essentially slamming the brakes on your entire digestive system. The nausea isn't just discomfort—it's your body telling you it can't process what's happening.

Can't eat → You're losing muscle.

When you're in a severe caloric deficit, your body doesn't just burn fat. It breaks down muscle tissue for amino acids through a process called gluconeogenesis—literally converting protein into glucose for energy. Muscle is metabolically expensive for your body to maintain, so when resources are scarce, it's one of the first things to go.

And for those of you on tirzepatide specifically—this is even more pronounced. Tirzepatide is a dual agonist hitting GLP-1 and GIP receptors, but it has no glucagon receptor activity. Retatrutide, on the other hand, is a triple agonist that includes glucagon receptor activation. Why does this matter? Glucagon signaling helps mobilize fat for energy and has some muscle-sparing properties. Without that glucagon component, tirzepatide users need to be even MORE intentional about protein intake and resistance training to protect lean mass.

Can't train or weight lift because you're too tired → You're killing your metabolic rate.

Here's where it gets ugly. Your basal metabolic rate (BMR)—the calories you burn just existing—is largely determined by your lean muscle mass. Every pound of muscle you lose reduces your daily caloric burn.

Now look—I'll be honest. A lot of people in the fitness space overexaggerate metabolic adaptation. Your metabolism doesn't just tank overnight because you skipped a meal or had a rough week. The body is more resilient than the fear-mongering suggests.

BUT. When you're eating next to nothing AND doing zero exercise for extended periods? It absolutely will happen. You're sending your body every possible signal that resources are scarce and muscle is expendable. Your thyroid downregulates, your NEAT (non-exercise activity thermogenesis) drops, and your body becomes ruthlessly efficient at conserving energy.

You're not just losing weight at that point—you're creating the exact metabolic dysfunction that made weight loss hard in the first place. And digging yourself out of that hole takes time.

Start low with ALL peptides and get the most out of the least.

Your GLP-1 receptors will desensitize over time with higher doses. Why burn through your sensitivity at 15mg when 5mg still works? You can always go up. You can't undo receptor downregulation overnight.

Eat 3-4 high protein meals a day. Stick to nutrient-dense foods.

Eggs, steak, chicken, vegetables, fruits. When you're coming from a metabolically dysfunctional state—insulin resistance, leptin resistance, years of yo-yo dieting—do you really think eating 300 calories a day is going to make you feel amazing?

There's going to be a time period where you need to provide your body with the resources it needs to rebuild. Your mitochondria need nutrients. Your hormones need building blocks. Your neurotransmitters need amino acids.

Use GLP-1s as the tool they are.

These peptides give you something powerful: the ability to say no to junk food without white-knuckling it. They quiet the food noise. But that's not permission to eat nothing—it's an opportunity to force yourself to eat whole, clean foods.

Address this NOW or you'll never build the habits to sustain your weight loss. It's that simple.

The neuroplasticity research is clear—your brain needs repetition to rewire. Every time you make a healthy choice while on these peptides, you're literally strengthening new neural pathways. Going slow through your weight loss journey gives you the time to build these connections. Rush it, and you'll hit your goal weight with the same broken habits you started with.

This is why slow and steady wins.

Not because it sounds nice. Because it's the only approach that actually works long-term.

Thank you to

@Laura PepFitCoach

for reminding me of the education needed in this space. The podcast should be out tomorrow and honestly it was one of the realest, most open conversations I've had about all of this.

Keep an eye out for it.

Compare Prices Research Use Only: https://peptideprice.store

Substack Post: https://open.substack.com/pub/derekpruski/p/do-glp-1s-the-right-wayyou-shouldnt?r=4jq1x8&utm_campaign=post&utm_medium=web&showWelcomeOnShare=true

Stay safe out there. 🙏

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