Retatrutide vs Tirzepatide

Two receptors against three

Tirzepatide agonises GIP and GLP-1; retatrutide adds glucagon, which raises energy expenditure rather than only suppressing intake. On paper that should win, and in phase 2 it did, with roughly 24% body weight lost over 48 weeks, with the curve still falling. The difference that matters is certainty. Tirzepatide is approved, with phase 3 data and a head-to- head win over semaglutide. Retatrutide has one phase 2 trial, no approval, and is already being sold as a research chemical on the strength of it.

A single composition of pancreatic islet cells adjacent to a blood capillary and surrounding acinar tissue, metabolic research subject.

Retatrutide Metabolic LY3437943, Triple G Full entry →

Two endocrine pancreatic cells with distinct subtle coral and navy vesicles next to a tiny capillary.

Tirzepatide Metabolic Mounjaro, Zepbound Full entry →

Retatrutide compared with Tirzepatide
	Retatrutide	Tirzepatide
Evidence behind it	Human trials	Human trials
Worth knowing	Not approved anywhere. Glucagon receptor activation raises heart rate more than the dual agonists do, and the long-term consequence of that is unknown. Everything currently sold is unapproved material of unverified identity, bought on the basis of one phase 2 trial.	The same gastrointestinal profile as semaglutide and the same boxed warning for thyroid C-cell tumours. Weight returns on stopping — SURMOUNT-4 showed substantial regain after withdrawal. Being newer, its long-term safety record is shorter than semaglutide's.
Approval	In trials	Approved · US & EU
Category	Metabolic	Metabolic
What it is	A triple agonist — GIP, GLP-1 and glucagon receptors together. Adding glucagon is the novel part: it raises energy expenditure rather than only reducing intake. Phase 2 produced the largest weight loss yet reported for a drug of this kind.	A 39-amino-acid peptide that hits two gut hormone receptors at once — GIP as well as GLP-1. That second target is what appears to separate it: in head-to-head trials it outperforms semaglutide on weight.
How it works	Agonist at three receptors at once. GLP-1 and GIP suppress appetite and improve insulin handling; glucagon receptor activation increases energy expenditure and drives hepatic fat breakdown — the combination attacks both sides of the energy balance.	A dual agonist at both the GIP and GLP-1 receptors. GLP-1 activation does what it does for semaglutide; adding GIP appears to improve insulin sensitivity and may blunt some of the nausea, though exactly why the combination works better is not settled.
What studies report	Around 24% mean body weight loss at 12 mg over 48 weeks in phase 2 — the highest reported for this class No weight-loss plateau by 48 weeks, unlike most trials of this kind Substantial reductions in liver fat in people with fatty liver disease Phase 3 trials are ongoing	Around 21% mean body weight loss at 15 mg weekly over 72 weeks in SURMOUNT-1 Beat semaglutide head-to-head in SURMOUNT-5, roughly 20% against 14% Superior HbA1c reduction to semaglutide 1 mg in SURPASS-2 Approved for obstructive sleep apnoea in obesity on the back of the SURMOUNT-OSA trials
Dosing	From studies 12 mg weekly, subcutaneous — Phase 2 obesity trial (n=338). −24.2% body weight; the curve had not flattened 8–12 mg weekly, subcutaneous — Phase 2 in type 2 diabetes. HbA1c and weight reductions exceeding comparators Reported, not evidence Circulating as a research chemical well ahead of approval, typically dosed in imitation of the trial schedule	From studies 15 mg weekly, subcutaneous — SURMOUNT-1, obesity (n=2,539). −20.9% body weight vs −3.1% placebo 10–15 mg weekly, subcutaneous — SURMOUNT-5, head-to-head against semaglutide 2.4 mg. ≈20% vs ≈14% weight loss 5–15 mg weekly, subcutaneous — SURPASS-2, type 2 diabetes. Greater HbA1c reduction than semaglutide 1 mg Reported, not evidence Titrated from 2.5 mg upward in 2.5 mg steps every four weeks Many stop climbing once an effective dose is reached rather than going to 15 mg
Why people take it	Weight lossType 2 diabetesFatty liver disease	Weight lossType 2 diabetesObstructive sleep apnoeaAppetite reduction
In practice	Already widely sold by research-chemical vendors despite being years from approval Attracts people who have plateaued on semaglutide or tirzepatide	Increasingly the first choice over semaglutide where cost and supply allow Same compounded and grey-market availability problem as semaglutide
Route	Subcutaneous injection, weekly	Subcutaneous injection, weekly

Rows describing reported use say what people do, not what has been shown to work. Evidence strength is graded the same way across the whole library, so the two columns are directly comparable.

Read the full entries

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