Retatrutide, heart rate and heart rhythm

Retatrutide makes the resting heart beat a little faster, and the effect grows with the dose. In the Phase 2 trial the rise peaked at about six months and then faded. Abnormal heart rhythms were reported more often on the drug than on placebo, though most were mild. The Phase 3 announcements have not yet given heart figures at all.

What the Phase 2 trial found

The 2023 Phase 2 trial in the New England Journal of Medicine followed 338 adults for 48 weeks. It reported a dose-dependent increase in resting heart rate on retatrutide. The increase was largest around week 24 and then declined towards the end of the trial.^[1]

The abstract does not state the size of the rise in beats per minute, so we will not put a precise number on it. Read alongside the licensed relatives of the drug (below), a few to about ten beats per minute at the higher doses is the honest range. Lilly's Phase 3 announcements for TRIUMPH-1, 2, 3 and 4 gave no heart-rate figure at all.^[2] Those numbers will only be public when the full papers are published, which is one reason the what we do not know yet list is still long.

Abnormal rhythms

The Phase 2 trial also counted arrhythmias, meaning any abnormal heart rhythm, from harmless extra beats to dangerous patterns. These were reported in 2% to 11% of participants across the retatrutide groups, against 2% on placebo. Most were mild or moderate.^[1]

One event was severe: a prolonged QT interval, which is a delay in the heart's electrical recovery that raises the risk of dangerous rhythms. That participant was also taking ondansetron, a widely used anti-sickness medicine that is itself known to prolong the QT interval.^[1] It is not possible to say from one case whether the drug, the ondansetron, or the combination was responsible. It is a reason to be careful about combining retatrutide-class drugs with QT-prolonging medicines, and it is why this site does not suggest anti-sickness medicines. See nausea, vomiting and gut effects.

Why heart rate rises

Two things are probably involved.

It is a class effect. All the GLP-1-based medicines raise resting heart rate a little. The Wegovy SmPC (the official UK product information) reports an average rise of 3 beats per minute from a baseline of 72 in the Phase 3 trials, and lists increased heart rate as an adverse reaction.^[3] The Mounjaro SmPC reports a maximum average rise of 3 to 5 beats per minute across doses in people with type 2 diabetes, against 1 on placebo, and also lists increased heart rate as a side effect.^[4]

Retatrutide adds a third target. Retatrutide also switches on the glucagon receptor, which its licensed relatives do not. Glucagon is the hormone thought to explain why the heart-rate rise with retatrutide looks larger and more dose-dependent than with earlier drugs, though the published data do not yet settle how much each part contributes. The how it works page explains the three targets.

Who should be extra cautious

The trial results cannot tell you what happens in people with existing heart problems, because the trials largely kept them out. The Phase 2 trial excluded anyone who had had a heart attack, stroke or hospital admission for heart failure in the previous three months, and anyone with uncontrolled high blood pressure.^[5] Trials of this kind also routinely screen out people with significant rhythm disease on their entry ECG. So the 2% to 11% arrhythmia figure comes from people with relatively healthy hearts.

Groups for whom a faster pulse or a rhythm change is a bigger deal include:

• people with an existing arrhythmia, such as atrial fibrillation;
• people with long QT syndrome, or a family history of it;
• people taking medicines that prolong the QT interval, which include some antibiotics, antidepressants, antipsychotics and anti-sickness drugs;
• people with heart failure, where a persistently faster heart rate adds to the strain on the heart.

Nobody in these groups has meaningful trial data on retatrutide. A clinician in a trial would adjust treatment; outside a trial there is no clinician and no known dose.

What an unlicensed vial changes

The heart-rate effect is dose-dependent. That is the single most important fact on this page when it comes to products sold online. Independent testing in Australia found a vial labelled 10 mg that actually contained about 19 mg of retatrutide.^[6] Someone injecting from that vial would be getting roughly double the effect they expected on their heart, as well as everything else, with no way of knowing. Other vials tested contained far less than labelled, or a different substance altogether; see what is actually in the vials.

Trial rates describe the trial product, given at a known dose with a clinician watching. An unlicensed product carries unknown extra risks on top of the drug's own effects, including contaminants that the trials never had to measure.