Tony Huge

Retatrutide and Heart Rate: What the Research Shows: Tony Huge’s Video Guide

Table of Contents

Retatrutide raises heart rate. Lilly published that in its own phase 2 trial. What the scare videos and the fan videos both miss, according to Tony Huge, is the question that actually decides things: if you push that number back down with a beta blocker, are you touching the thing that raised it? He walks through the trial data, the class comparison, the outcomes pool, and the glucagon receptor mechanism, then checks his own beta blocker protocol against the research and finds a problem with it.

Video: Retatrutide and Heart Rate: What the Research Actually Shows. Published August 20, 2026. Watch on YouTube.

What the video covers

What Lilly actually reported

Tony starts from the trial everyone quotes: the phase 2 obesity study in the New England Journal of Medicine, 2023, 338 people over 48 weeks with a placebo group. The top dose lost 24.2% of body weight against 2.1% on placebo, about 60 pounds for a 250 lb man and, in his words, the biggest weight loss number any compound has put on paper. Then the sentence people skip: a dose-dependent increase in heart rate that peaked at 24 weeks and declined thereafter, while the person was still taking the same dose.

How many beats? Tony cites a 2026 meta-analysis: at the top dose, about six beats per minute above baseline at week 48, measured after the peak had already receded; the week 24 peak must have been higher but is not published. The same analysis lined up the class across 12 trials and 15,313 patients: tirzepatide about two beats, liraglutide about 2.5, injected semaglutide about 3.5, retatrutide 3.46, and the outlier orforglipron at 7.3. The oral pill marketed as convenient moves heart rate more than double what retatrutide does.

Is the faster heart rate doing damage?

This is where Tony expected bad news and did not find it. He cites a 2025 Journal of the American College of Cardiology pooling of 21 randomized trials and 99,599 patients on this class: all-cause death down 12%, cardiovascular death down 13%, major cardiovascular events down 13%, heart attacks down 15%, heart failure down 15%. Every hard endpoint moved in the good direction while heart rate was going up. He does not call a faster pulse good; he says the thing people fear has been measured in nearly 100,000 patients and the benefits outweighed it. Two honest exceptions: in a separate 56-trial pool, the highest-dose groups had 1.63 times the rate of ventricular arrhythmia, and so did people who started at the highest body weight.

The mechanism is the hinge of the video. In 2025, a group applied retatrutide directly to still-beating heart tissue and worked out which receptor it was hitting. It was not the GLP-1 component. It was the glucagon component: block the glucagon receptor and the speeding up stopped. Retatrutide is talking to the heart’s natural pacemaker through the glucagon receptor, raising cyclic AMP inside those cells so they fire faster.

The pulse is a gauge, not the engine

Everyone wants the raised heart rate to mean extra calories. Tony’s analogy is a car’s tachometer: it reads how hard the engine is working, and moving the needle is not the same as changing the engine. Adrenergic drive does raise calorie burn, and he has built fat loss protocols on it, but he could not find a study quantifying what a raised resting heart rate burns; what exists uses heart rate as a stand-in for oxygen uptake during training.

“Your pulse is a gauge. Moving the needle is not the same as changing the engine.”

Tony Huge, 07:30

So where did 24.2% come from? Appetite. Tony cites a GLP-1 meta-analysis finding no increase in resting energy expenditure, with two of three trials showing post-meal calorie burn went down. Retatrutide’s glucagon arm was supposed to add fat burning; in mice it does. In humans, a glucagon infusion was tested in a sealed metabolic chamber measuring every calorie for 72 hours, and sleeping, resting, and 24-hour burn showed no difference at any time point. His conclusion is that retatrutide should be sold as what it is, the best appetite suppressant anyone has produced.

Beta blockers: selectivity and timing

Tony’s clients bring heart rate down with nebivolol, and years before retatrutide existed he used propranolol at bedtime and nebivolol on himself, both prescription drugs used off label under supervision. Then he checks his homework. There are three beta receptors. Beta 1 is mostly in the heart; block it and heart rate drops. Beta 2 is on the lungs and in fat cells, and probes placed inside human belly fat show beta 1 and beta 2 together drive fat release. A drug blocking beta 1 only lowers heart rate. A drug blocking both lowers heart rate and clamps fat cells shut.

Propranolol blocks both. Tony cites the numbers: resting metabolic rate 276 calories a day lower under beta blockade, suppressed fat release during exercise, maximal oxygen uptake down 5 to 15%, and a two-month training study where the propranolol group showed no improvement in exercise capacity while the heart-selective and placebo groups both improved. His historical workaround was timing: propranolol has a 3 to 6 hour active life, so a bedtime dose was gone by the next day’s training. He reports better sleep and a lower nighttime heart rate with no cost to fat loss, and flags that propranolol carries the class’s highest signal for nightmares and psychiatric effects.

Nebivolol is different by design: beta 1 selective, leaving beta 2 in fat and airways largely alone, and activating beta 3, which is where its vasodilation comes from. Tony cites a 2012 head-to-head in 46 people with metabolic syndrome where nebivolol and metoprolol dropped heart rate equally, metoprolol degraded insulin sensitivity, and nebivolol did not; a six-month study in 72 people found the same split; a 1992 treadmill crossover found atenolol cut exercise capacity while nebivolol did not; and an uncontrolled 5,031-patient study saw weight go down where the class reputation is gain. Its half-life is about 11 hours, so the bedtime trick does not apply; with nebivolol, selectivity protects fat loss rather than timing.

The result that undercuts his own protocol

Back to the 2025 beating-heart experiment. The researchers also applied propranolol to it, and propranolol did not weaken retatrutide’s effect at all. The same result appeared in pigs with a related compound, where blocking alpha and beta receptors together still failed to stop it. Tony says outright that this undercuts his protocol. A beta blocker lowers resting heart rate through its own route, but it is not undoing what retatrutide does through the glucagon receptor.

His fallback is practical rather than mechanistic. Heart rate rises during the day from many inputs stacked together, and a beta blocker still blocks the others. For bodybuilders on growth hormone and insulin, or carrying a lot of weight or water, that reduction in total cardiac stress may still matter. For someone on retatrutide alone, the outcome data suggests the increase may simply be acceptable.

Cheat Sheet Pivot

What Tony reported doing historically and what the cited trials used. He is explicit that these are prescription drugs, that his account is storytelling rather than advice, and that he does not currently pair a beta blocker with retatrutide alone.

  • Historically Tony took propranolol at bedtime, chosen for its short active life, and nebivolol during periods on stimulants and testosterone.
  • His clients use nebivolol, which he prefers for its beta 1 selectivity and the insulin sensitivity data.
  • The retatrutide trial data he cites: heart rate peaked at 24 weeks, sat about six beats above baseline at week 48 at the top dose, and hard outcomes across the class improved.
  • Risks he lists: propranolol is a hard no with asthma (nonselective blockade cut FEV1 10.2% in a 2014 meta-analysis); beta blockers raised the odds of hospitalized hypoglycemia 1.87 times in 26,545 patients and hide its warning signs, which matters for anyone using insulin; slowing the heart too much is its own problem; daytime nonselective blockade costs metabolism and training.
  • His current position: he would use a beta blocker on retatrutide only if other heart-rate-raising compounds were in the picture, and probably not otherwise.

Retatrutide and the GLP-1 class are indexed in the Miracle Molecules Cheat Sheet. For the muscle side of this compound class, read GLP-1 Muscle Loss: What Pharmacists Won’t Tell You. For the cardiovascular marker Tony thinks lifters underrate most, see Blood Pressure: The Most Underrated Risk in Lifting.

Where the evidence stops

Retatrutide is not approved. It is in phase 3 with over 5,800 people enrolled and no final results, which Tony says is exactly why the safety information needs to be laid out somewhere. The 99,599-patient outcomes pool is for the class, not retatrutide specifically, and the week 24 peak heart rate has not been published. The beta blocker studies he cites are in hypertension, metabolic syndrome, and healthy volunteers, not in people taking retatrutide. And the one experiment that tested the combination directly, on beating heart tissue, found the beta blocker does not touch retatrutide’s mechanism. Tony’s bedtime propranolol experience is one person’s account, and he labels it that way.

Keep going

For the broader weight loss peptide landscape, read Peptides for Weight Loss: Tony Huge’s Expert Analysis. Companion articles for each new video reach the tonyhuge.is email list first, and the full peptide archive is at tonyhuge.is.

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