Pull up a chair for this one Brosefus...

...because the GLP-1 conversation right now feels like watching a casino commercial at 2 AM.
​
Bright lights. Big promises. Nobody talking about the hangover.

Everyone’s yelling about weight loss.
Everyone’s high-fiving blood sugar improvements.
Everyone’s marveling at how food suddenly loses its psychic grip on your soul.

And all of those things are important and amazing...

...but almost nobody is talking about what these drugs do to your nervous system.

Not because it’s secret.
Not because it’s controversial.
But because it doesn’t fit neatly on a billboard.
Plus very few people roaming the cardio equipment at PF are reading the actual peer reviewed research.

The boring stuff always gets ignored first.
Until it doesn’t.

One of those boring signals?

Resting heart rate (RHR).

Grab both glute cheeks and prepare as....

...GLP-1–based drugs raise resting heart rate.

Not “might.”
Not “in theory.”
Not “according to my wearable after margaritas.”

It’s in the trials — repeatedly — across different drugs and different populations (Marso et al., 2016a; Marso et al., 2016b; Wilding et al., 2021; Sun et al., 2015).

Here is what one person emailed me
​
​"I’ve pulled the Reta for a couple of weeks and now my resting heart rate went back down by 15 bpm to just under 50 bpm and HRV bounced upwards by 10"

I've seen this in my own clients and consults for almost 2 years now.

Once you see it, you can’t unsee it.

Across multiple large randomized trials, resting heart rate climbs by roughly 2–7 beats per minute.
​
The effect is dose-dependent, shows up even when weight loss is controlled for, and — importantly — reverses when the drug is discontinued (Sun et al., 2015; Jastreboff et al., 2023).

That last part is important. Circle it. Tattoo it on your forehead if needed.

Because resting heart rate isn’t just a number your watch spits out to keep you emotionally unstable.

It’s an autonomic signal.

When resting heart rate creeps up chronically, parasympathetic (vagal) tone usually slides downhill.

Recovery starts to wobble. HRV tends to sink like a rock tied to a kettlebell even thought most GLP-1 trials didn’t measure HRV directly (Marso et al., 2016a; Wilding et al., 2021).

However, that doesn’t mean HRV stopped existing.
It just means the studies didn’t look.

Physiology doesn’t care what your spreadsheet includes.

If your nervous system is quietly nudged toward “always on,” and "SQUIRREL!" something else has to eat the cost.

So what’s actually pushing heart rate up?

Several mechanisms, all pulling in the same direction.

GLP-1 receptors are expressed at the sinoatrial node, directly influencing chronotropy (aka HR for the BroZ).

Add evidence of reduced parasympathetic tone and mild sympathetic activation, and you’ve already got upward pressure on heart rate (Sun et al., 2015).

Then the newer drugs show up wearing steel-toed boots.

Triple agonists like retatrutide activate the glucagon receptor — increasing metabolic drive and heart rate together — which likely explains the larger HR increases seen in phase-2 data (Jastreboff et al., 2023).

Different molecules. Same destination.

The trials don’t whisper about this.

In the LEADER trial, liraglutide increased resting heart rate by ~2–4 bpm, and the effect persisted throughout therapy (Marso et al., 2016a).

In SUSTAIN-6, semaglutide increased resting heart rate by ~2–6 bpm, even while overall cardiovascular outcomes were favorable (Marso et al., 2016b).

In STEP-1 — non-diabetic adults with obesity — resting heart rate still rose ~2–4 bpm, confirming this is not a diabetes-only phenomenon (Wilding et al., 2021).

Zooming out further, meta-analyses confirm this as a class effect across GLP-1 receptor agonists versus placebo (Sun et al., 2015).

And retatrutide?

That one cranks the volume further by about 5–7 bpm, dose-dependent, very likely amplified by glucagon receptor activity (Jastreboff et al., 2023).

At some point this stops being “interesting” and starts being “obvious.”

Now here’s where the internet usually goes feral.

People argue.
Teams form.
Someone screams “fear-mongering.”
Someone else screams “Big Pharma.”

Meanwhile the physiology just sits there, unimpressed.

Because here’s the reality:

The heart-rate increase is reversible.

Across trials and mechanistic data, resting heart rate trends back toward baseline within roughly 1–4 weeks after stopping the drug (Sun et al., 2015; Jastreboff et al., 2023).

Which lines up beautifully with real-world wearable data showing resting HR falling and HRV rebounding once the drug comes off board.

This is a great thing since it hints that the effect is only when taking the medication and normalizes post.

Again, my goal here is to education you with actual data and not yell that the sky is falling or to tell you it is all rainbow colored unicorn farts.

So what’s the honest takeaway — no marketing department involved?

GLP-1 drugs raise resting heart rate.
That reflects a real autonomic shift.
It’s usually not dangerous.

But it can matter.

Especially if you train hard.
Especially if you care about recovery.
Especially if your calendar already looks like a war crime.

If your only goal is watching the scale drop, you can probably ignore this and keep rolling.

If your goal includes performance, resilience, or not slow-roasting your nervous system on low heat, it’s worth paying attention.

Weight loss is the benefit.
Autonomic cost is part of the trade-off.

That’s not a scare tactic.
That’s biology doing biology things.

Much love,
Mike

PS- This is exactly the kind of situation where direct access to me saves time.

When resting heart rate creeps up and you can’t tell if it’s the drug, training load, sleep, stress, under-fueling, or some unholy blend of all five — guessing is slow. Or heck, maybe you had no idea GLP1s could even increase RHR.

Inside Applied Growth 2026, you get direct access to me through a simple framework so we can troubleshoot things like this fast. Strip the noise. Find the bottleneck. Decide what actually matters now.

Physiology always collects the bill.
The only question is how long you let it sit unpaid.
​>> Applied Growth 2026 << full details

References

Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., et al. (2016a). Liraglutide and cardiovascular outcomes in type 2 diabetes. New England Journal of Medicine, 375(4), 311–322. https://doi.org/10.1056/NEJMoa1603827

Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., et al. (2016b). Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine, 375(19), 1834–1844. https://doi.org/10.1056/NEJMoa1607141

Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMoa2032183

Sun, F., Wu, S., Guo, S., Yu, K., Yang, Z., Li, L., & Zhang, Y. (2015). Effect of glucagon-like peptide-1 receptor agonists on heart rate: A meta-analysis of randomized controlled trials. Diabetes Research and Clinical Practice, 110(1), 26–37. https://doi.org/10.1016/j.diabres.2015.08.015

Jastreboff, A. M., Kaplan, L. M., Frías, J. P., Wu, Q., Du, Y., Gurbuz, S., et al. (2023). Triple-hormone receptor agonist retatrutide for obesity: A phase 2 trial. New England Journal of Medicine, 389(6), 514–526. https://doi.org/10.1056/NEJMoa2301972

_____________________

Mike T Nelson CISSN, CSCS, MSME, PhD
Associate Professor, Carrick Institute
Owner, Extreme Human Performance, LLC
Editorial Board Member, STRONG Fitness Mag
​​Mike T Nelson is a Ph.D. and not a physician or registered dietitian. The contents of this email should not be taken as medical advice. It is not intended to diagnose, treat, cure, or prevent any health problem - nor is it intended to replace the advice of a physician. Always consult your physician or qualified health professional on any matters regarding your health.

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