Tirzepatide vs Semaglutide vs Retatrutide: what's actually different
The three peptides driving global GLP-1 demand are mechanistically distinct. This guide compares the receptor pharmacology, the actual trial endpoints, and what independent lab testing has revealed about the Australian market for each.
The receptors: what each peptide actually does
Semaglutide: single agonist at the GLP-1 receptor. The original and most widely studied of the three.
Tirzepatide: dual agonist at GIP and GLP-1 receptors. Adding GIP changes the metabolic profile and the side-effect curve.
Retatrutide: triple agonist at GIP, GLP-1, and glucagon receptors. Glucagon agonism is the differentiator. It increases energy expenditure on top of appetite reduction.
Published trial endpoints
All three have published phase 2 or phase 3 data. Reported mean weight-loss endpoints at the highest studied doses (approximate, varies by trial duration and population):
Semaglutide: ~14-17% body weight at 68 weeks (STEP trials).
Tirzepatide: ~20-22% body weight at 72 weeks (SURMOUNT trials).
Retatrutide: ~24% body weight at 48 weeks (phase 2). Phase 3 still recruiting at time of writing.
These are population means from controlled trials, not what any individual will see, and not a guarantee of safety at unsupervised doses.
Half-life and dosing rhythm
All three are designed for weekly subcutaneous dosing. Half-lives are roughly 5-7 days for semaglutide, ~5 days for tirzepatide, and ~6 days for retatrutide. Weekly dosing schedules reflect this. Daily injection of any of these is a dead giveaway someone is following a dosing protocol from an unreliable source.
Vendor reality in the Australian market
Independent CoAs collected on LabDoc show meaningful purity dispersion across all three. Headline observations:
Semaglutide: most heavily counterfeited because demand is highest. Identity failures (vial doesn't contain semaglutide at all) are not rare in CoA data.
Tirzepatide: purity is generally good among established vendors; peptide content (mg per vial) varies more than label suggests.
Retatrutide: newest of the three, smallest sample size, highest variability. Several vendors are shipping product with no identity test on file.
Identity confirmation (LC-MS): non-negotiable for retatrutide given the counterfeiting rate on newer compounds.
Peptide content vs label mg, particularly important for tirzepatide where under-fill is common.
Frequently asked questions
Which has the strongest weight-loss data?
Retatrutide reported the largest mean weight loss in phase 2 (~24%), ahead of tirzepatide (~20-22%) and semaglutide (~14-17%). Phase 3 data for retatrutide is still maturing.
Are these peptides interchangeable?
No. Different receptor profiles produce different metabolic, gastrointestinal, and cardiovascular effects. They are not 'stronger' versions of each other.
Why does retatrutide CoA quality vary more?
It's the newest and least-supplied of the three, so manufacturing experience is uneven and counterfeiting is harder to detect without a verified identity test.