Why These Three?

Semaglutide, tirzepatide, and retatrutide are the three peptides defining the modern weight-loss field. They share the same biological family — incretin-mimetic peptides — but each one targets a different combination of receptors, and the trial results scale almost linearly with how many pathways they engage.

Semaglutide arrived first. Eli Lilly’s tirzepatide added a second receptor and produced bigger results. Retatrutide is the third generation — adds a third receptor, produces the biggest results yet recorded. Whether you’re researching the field or evaluating compounds for laboratory work, these three are the reference points everything else gets compared against.

The Three Compounds at a Glance

Side-by-Side Comparison

A note on comparing trials directly: the weight loss numbers above come from each compound’s flagship trial, but trial designs aren’t perfectly identical. Retatrutide’s 24.2% is a 48-week Phase 2 figure; semaglutide and tirzepatide’s numbers come from longer Phase 3 trials. The direct head-to-head Phase 3 trial of retatrutide hasn’t reported yet — when it does, expect the numbers to update slightly. The hierarchy (retatrutide > tirzepatide > semaglutide) is unlikely to change.

The Glucagon Difference

The single biggest distinction between retatrutide and the other two is that retatrutide engages the glucagon receptor and the others don’t. This matters more than the basic “more receptors = more weight loss” story suggests.

GLP-1 and GIP work mostly on the input side of energy balance: appetite suppression, slower gastric emptying, better insulin response. They make you eat less. Glucagon works on the output side: it increases energy expenditure and clears fat from the liver. It doesn’t just make you eat less — it makes your body burn more.

This is why retatrutide produces results that GLP-1-only and GLP-1+GIP drugs can’t match in three specific areas:

Resting metabolic rate. Most weight loss reduces resting energy expenditure — your body adapts by burning less. Retatrutide appears to maintain or even increase it. The glucagon receptor activity counteracts the metabolic adaptation that normally accompanies major weight loss.

Liver fat clearance. The liver is glucagon’s primary site of action. In Eli Lilly’s NAFLD sub-study published in Nature Medicine in 2024, retatrutide produced an 81.4% mean reduction in liver fat content at the highest dose. 86% of participants achieved complete liver fat normalisation. Tirzepatide produces meaningful but smaller liver fat reductions; semaglutide produces modest ones.

The high-responder tail. 26% of retatrutide participants lost ≥30% of their body weight. That category essentially didn’t exist for semaglutide or tirzepatide at this scale. The glucagon receptor seems to unlock a top-end response that single- and dual-agonist drugs cap out before reaching.

Side Effects: Closer Than You’d Expect

A common assumption: a triple agonist must have triple the side effects. The trial data doesn’t show this. The side effect profiles of semaglutide, tirzepatide, and retatrutide are remarkably similar — overwhelmingly gastrointestinal, mostly mild to moderate, dose-dependent across all three.

In all three compounds, the most common side effects are nausea, diarrhoea, vomiting, and constipation. Most subside as the body adapts to the dose. This is why titration matters — starting low and increasing every 4 weeks reduces gastrointestinal severity by an order of magnitude compared with starting at the full dose.

Where retatrutide differs slightly is heart rate. The glucagon receptor activity produces small but consistent increases in resting heart rate (around 5 bpm at the highest dose in the Phase 2 trial). This is a known glucagon effect and is being monitored carefully in Phase 3 trials. Whether it represents a clinical concern at scale is one of the open questions Phase 3 will answer.

All three compounds carry a black-box-style warning for thyroid C-cell tumours observed in rodent studies. Whether this translates to human risk is unknown — there’s no human evidence of increased thyroid cancer risk for any of the three at this point, but the warning remains as a precaution.

Which One Is Best for What?

For research applications specifically — and to be clear, all three of these compounds are supplied by Bangkok Peptides as research peptides for laboratory use only — different research questions favour different compounds:

The interesting research models are increasingly the comparative ones — running the same experimental design across all three compounds to isolate exactly what each receptor pathway contributes to the overall effect. This is where the field is heading, and it’s the reason all three compounds are now stocked alongside each other in research peptide catalogues globally.

Availability and Practical Differences

For non-research access, the three compounds differ significantly in how they reach end users.

Semaglutide is widely available globally as a prescription medicine. Branded as Ozempic for diabetes and Wegovy for weight loss, with Rybelsus as the oral form. Generic semaglutide is available in some markets through compounding pharmacies, though regulatory status varies by jurisdiction. Cost varies enormously — Wegovy retails around $1,300/month in the US; Ozempic similar.

Tirzepatide is similarly available as Mounjaro for diabetes and Zepbound for weight loss. Eli Lilly produces both. Compounded tirzepatide became widely available in the US during the supply shortage of 2023–2024 but FDA action since has restricted that. Retail pricing in the US sits around $1,000/month for Zepbound.

Retatrutide isn’t approved as a medicine anywhere. It’s not available through pharmacies. The compound supplied by Bangkok Peptides and other research peptide vendors is the same molecule being studied in Eli Lilly’s Phase 3 trials — supplied strictly for laboratory and preclinical research use only, not for human consumption.

Bangkok Peptides supplies retatrutide in Thailand at our retatrutide product page, in 10mg, 20mg, and 30mg vial strengths, with same-day Bangkok dispatch and tracked nationwide delivery. See our Retatrutide Thailand page for domestic supply details.

Frequently Asked Questions