Semaglutide vs Tirzepatide vs Retatrutide

These three compounds are often mentioned in the same breath because they work on the same family of gut-hormone receptors and are marketed, unregulated, through the same South African "research chemical" channels. But they're at very different regulatory stages, and they don't cost the same. This page is a fast side-by-side — for the full mechanism, trial data and sourcing on any one compound, see its own guide.

At a glance

Prices are what the vendors we've verified publish for each compound as of this page's last update: semaglutide from New You Lab, Peptide Labs South Africa and ReGen-X; tirzepatide from Peptide Labs South Africa and Noventra Pharma; retatrutide from ReGen-X, Peptide Labs South Africa and Noventra Pharma. See each guide's own "Cost in South Africa" section for the specific dose behind each figure.

Mechanism, in one line each

• Semaglutide activates one receptor: GLP-1. See how it works.
• Tirzepatide activates two: GIP and GLP-1 — the "twincretin" mechanism, often discussed as more potent than a single-receptor drug in head-to-head trial comparisons. See how it works.
• Retatrutide activates three: GIP, GLP-1, and glucagon — the added glucagon-receptor activity is theorized to increase energy expenditure on top of the appetite and insulin effects the other two share.

Regulatory status, side by side

Semaglutide and tirzepatide are both registered medicines in some markets, dispensed by a pharmacist against a prescription. Retatrutide has no regulatory approval anywhere in the world, for any use — it's still in Phase 3 trials. None of that changes what's sold online in South Africa as a "research chemical": vials marketed under all three names are not SAHPRA-registered medicines, and SAHPRA has publicly warned against unregistered peptide products sold this way. A prescription product going through a pharmacy is a legally and practically different item from an unregulated vial bought online, regardless of which of the three compounds it claims to be.

Trial weight-loss data, side by side

Semaglutide's pivotal STEP program reported average weight loss on the order of 15% of body weight over roughly a year and a half, under medical supervision. Tirzepatide's pivotal SURMOUNT-1 trial reported mean weight loss of 15.0%–20.9% at 72 weeks depending on dose (versus 3.1% on placebo) — the highest confirmed figure of the three, from the most mature trial of the three. Retatrutide's Phase 2 trial reported mean weight reduction of up to 17.5% at 24 weeks and 24.2% at 48 weeks on its highest dose — a higher number than either approved drug's, but from an earlier-stage, smaller trial, so that data is less complete than an approved drug's. See each compound's own guide for the full numbers and sources behind these figures.

Which one is "better"?

We're not going to answer that, and you should be skeptical of anyone who does with confidence — including a vendor selling one of them. Semaglutide and tirzepatide carry similar gastrointestinal side effects and the same class-wide boxed warning about thyroid C-cell tumors seen in rodent studies. Retatrutide's Phase 2 trial reported a broadly similar GI side-effect pattern, but it has no approved label and so no confirmed boxed warning or complete safety profile yet (see each guide's Side effects section for what's actually known about each). Which compound, dose and format suits a given person is exactly the kind of decision a prescriber makes after screening for the contraindications on the label — a decision an unsupervised online purchase skips regardless of which of the three names is on the vial.

Frequently asked questions

Related guides

This page is educational information comparing three molecules and their regulatory histories. It is not medical advice, not a recommendation to use any of these compounds outside a prescription, and not an endorsement of any vendor.