Why Am I So Tired on Retatrutide?

Happy Monday!

Today, I want to delve into a question I received from a reader in my question box.

I am starting to see more questions like this as more people experiment with GLP-1s like retatrutide:

Let’s break this down—why GLP-1s like retatrutide can make you feel like you’ve just finished running a marathon, and, most importantly, what you can do to get your energy (and your life) back on track.

The Most Common Cause—Rapid Calorie Deficit

First, let’s start with the obvious: GLP-1 peptides are appetite silencers for your brain.

You eat less—sometimes way less—without even realizing it.

And while this is fantastic for the scale, it’s a double-edged sword for your energy. Most people on retatrutide cut calories by 20–40% compared to before.

That means your body’s “fuel gauge” is on empty.

When you go from filling up the tank with 2,500 calories a day to barely scraping 1,200–1,400, your cells are running on fumes.

You simply can’t make as much energy—ATP, for my biochemistry nerds—so you feel tired, sluggish, and foggy.

If you’re not strategic with food choices, especially protein and micronutrients, this feeling can get worse over time, not better.

Losing Muscle Mass

When you lose weight fast (and especially when you don’t eat enough protein or skip resistance training), you’re burning muscle, too.

Data from clinical studies show that up to 25–40% of weight lost on GLP-1s comes from lean body mass.

Why does this matter? Muscle is your metabolic engine.

Lose too much of it, and not only does your metabolism slow to a crawl, but your body literally can’t generate energy as efficiently.

Less muscle means less glucose disposal, lower mitochondrial output, and you feel it every time you try to move.

If you’re not lifting weights or prioritizing protein, you’re putting yourself on the fast track to fatigue.

The Electrolyte and Hydration Trap

Now, let’s talk about something almost no one pays attention to: electrolytes and hydration.

When you cut food volume dramatically, you’re also cutting out the salt, potassium, and magnesium that came with your food.

Many people also unconsciously drink less water, thanks to that “delayed stomach emptying” effect GLP-1s are famous for.

Result?

Mild dehydration and electrolyte imbalance.

Symptoms look suspiciously like “keto flu”—headache, muscle weakness, irritability, and, you guessed it, fatigue.

For many, adding a quality electrolyte supplement (think ElectraShred from Unmatched Supps, Redmond sea salt, or a DIY mix of salt and potassium) instantly upgrades their energy.

Hydration is non-negotiable; 80–100 ounces of water a day is a bare minimum.

Hormones—Thyroid, Sex Hormones, and Cortisol

When you’re on retatrutide, your body senses an energy crisis.

One of the first things it does is slow down the thyroid, particularly T3—the active thyroid hormone that regulates energy production.

For some, especially those with pre-existing thyroid issues, this is enough to feel like you’ve hit a wall.

Add in drops in testosterone (for men and women) and estradiol, both of which are sensitive to rapid weight loss and calorie restriction, and you’ve got the perfect recipe for “blah.”

Not to mention, the stress of weight loss can spike cortisol, giving you that weird combination of being wired but tired—or just plain exhausted.

Hypoglycemia and Blood Sugar Swings

GLP-1s, by design, boost insulin after meals and suppress glucagon.

That’s good for blood sugar, but when you’re not eating much, your blood glucose can drop lower than you’re used to.

This isn’t classic “passing out” hypoglycemia, but more of a subtle, steady low—just enough to make you tired, foggy, and irritable.

If you ever feel better after a salty carb snack, this might be what’s going on.

Combine this with changes in gut motility (slower digestion, constipation, or nausea), and your brain is screaming for more fuel, even if you aren’t technically “hungry.”

The Inflammatory Detox and Mitochondrial Slowdown

As you burn fat, your body releases stored toxins, inflammatory molecules, and free fatty acids into the bloodstream.

For some, especially those losing a lot of weight quickly, this can feel like a mild “detox” crash—tired, headachy, a bit off.

Simultaneously, your mitochondria (the engines in your cells) start downregulating because they’re not getting as much fuel to burn.

Over time, this can mean less ATP is produced, so everything slows down.

It’s like running your iPhone on low-power mode: It still works, but everything’s a little slower.

What You Can Do

Okay, so you’re tired.

What can you do about it?

Here’s my field-tested protocol:

1. Prioritize Protein: Minimum 0.8–1 gram per pound of ideal body weight. If you weigh 180 lbs, eat at least 150 grams of protein a day. This preserves muscle and keeps your metabolism up.

2. Lift Heavy, Lift Often: Resistance train at least 3–4 times per week. No, walking doesn’t count. You need to send a signal to your body to hold onto muscle.

3. Hydrate and Add Electrolytes: Drink 80–100 ounces of water every day. Add electrolyte supplements or make your own with salt and potassium.

4. Strategic Refeeds: Once per week, have a “maintenance” calorie day. Prioritize clean carbs and protein to restore energy and hormone balance.

5. Check Your Labs: If fatigue doesn’t improve after 4–6 weeks, get your thyroid, testosterone, and cortisol checked.

6. Use GH Peptides and Mitochondrial Peptides: These can help muscle recovery and mitochondrial function—especially during aggressive fat loss phases.

My Takeaway

If you’re experiencing fatigue on retatrutide, you’re not broken.

You’re adapting.

GLP-1s are powerful tools, but they only work as well as your foundations—nutrition, hydration, resistance training, and hormone balance.

Remember, the fatigue is almost always temporary.

Most people feel it hardest during the first month, then gradually adapt as their body finds a new normal.

With a little intention and some tweaks, you can power through the rough patch and come out the other side not just lighter, but stronger and more energetic than you’ve been in years.

Best,

Hunter Williams