Two of the most-discussed peptides in UK weight management. Here's where each one sits on the evidence — without the marketing.
Mounjaro · Zepbound · LY3298176
Wegovy · Ozempic · Rybelsus
The headline numbers, side by side.
| Tirzepatide | Semaglutide | |
|---|---|---|
| Mechanism | Dual GIP + GLP-1 agonist | GLP-1 agonist |
| Manufacturer | Eli Lilly | Novo Nordisk |
| Approval (UK obesity) | 2023 | 2021 |
| Mean weight reduction | −20.9% at 15mg (72w) | −14.9% at 2.4mg (68w) |
| HbA1c reduction (T2D) | −2.30% at 15mg | −1.86% at 1mg |
| Maximum weekly dose | 15 mg | 2.4 mg (obesity) |
| Trials reviewed | 42 | 67 |
The same gut-hormone family — but tirzepatide pulls on two levers, not one.
Both compounds belong to the incretin class. Semaglutide is a long-acting GLP-1 receptor agonist: it potentiates insulin release, suppresses glucagon, slows gastric emptying, and signals satiety. Tirzepatide does all of that plus simultaneously activates the GIP receptor — the body's other major incretin pathway. This dual agonism appears genuinely additive: SURPASS-2 found tirzepatide outperformed semaglutide on every primary endpoint, at every matched dose level[1].
Tirzepatide produces larger effects on average. Semaglutide has more long-term data.
In the head-to-head SURPASS-2 trial, tirzepatide 15mg produced ~3.5x the absolute weight reduction of semaglutide 1mg over 40 weeks[1]. Across the SURMOUNT and STEP programs, mean reductions at the highest approved obesity doses are roughly −20.9% (tirzepatide) versus −14.9% (semaglutide) — both vastly exceeding any prior pharmacologic agent in this class.
Semaglutide, however, has the larger long-term safety dataset, more years of post-marketing surveillance, and a completed cardiovascular outcomes trial (SELECT) showing a 20% MACE reduction in patients with established cardiovascular disease[2]. The equivalent tirzepatide trial (SURPASS-CVOT) reads out in 2026–2027.
Profiles are broadly similar — GI-dominated and dose-dependent.
| Effect | Tirzepatide | Semaglutide |
|---|---|---|
| Nausea | 30–40% | 30–44% |
| Diarrhoea | 15–22% | 17–30% |
| Constipation | 10–18% | 11–24% |
| Vomiting | 9–13% | 10–24% |
| Discontinuation rate | ~6% | ~7% |
| Acute pancreatitis | <0.5% | <0.5% |
Identical regulatory category. Different real-world supply pictures.
Both are prescription-only medicines (POM) under the Human Medicines Regulations 2012. Both are licensed for type-2 diabetes and chronic weight management. Both can be obtained through NHS pathways (with strict eligibility) or via regulated private clinics with prescriber assessment.
The MHRA has issued counterfeit warnings for both products in 2024–2025. Tirzepatide's higher demand-vs-supply gap has driven a particularly active grey market — with documented cases of injector pens containing wrong doses, unsterile contents, or entirely different active ingredients[3].
Indicative monthly figures from regulated private prescribers, May 2026.
| Dose tier | Tirzepatide | Semaglutide |
|---|---|---|
| Starter | £170 / month | £140 / month |
| Mid-range | £220 / month | £190 / month |
| Maximum dose | £260 / month | £240 / month |
On a pure evidence-of-effect basis, tirzepatide produces larger mean reductions on every primary endpoint that has been measured head-to-head. The dual-incretin mechanism is no longer hypothetical — it's the most plausible explanation for the observed delta. For most readers asking "which one works better?", the honest answer is tirzepatide.
That said, semaglutide has earned a longer track record. The SELECT cardiovascular data is meaningful for anyone with established CVD; the equivalent tirzepatide data isn't published yet. Semaglutide's supply chain is also more stable, which matters more than it should given how disruptive forced switches are.
Body-composition outcomes are your primary endpoint, you can tolerate the titration schedule, and you have reliable supply through a regulated route.
You have established cardiovascular disease, you're prioritising the longer evidence base, or supply continuity matters more than peak effect size for you.
This verdict reflects the published evidence as of 2 May 2026. We update comparison pages whenever new phase-3 data is published.