Editorial commentary on published literature
Tirzepatide and semaglutide: what the published trial data and UK regulatory record report
This page is editorial commentary on the published clinical literature for two GLP-1 receptor agonist medicines licensed in the UK for weight management: tirzepatide (marketed as Mounjaro by Eli Lilly) and semaglutide (marketed as Wegovy by Novo Nordisk). It summarises what the SURMOUNT-1, STEP-1 and SURPASS-2 trials reported, references the NICE technology appraisals (TA1026, TA875) and the MHRA licensing record, and notes the NHS access pathway. Both are prescription-only medicines. PeptideClear does not recommend a medicine for any individual. Any prescribing decision is between a patient and a UK-licensed prescriber.
Published trial outcomes referenced on this page
- · SURMOUNT-1 (tirzepatide, weight management, N Engl J Med 2022, PMID 35658024). Mean body weight reduction reported at 72 weeks in adults with overweight or obesity without type 2 diabetes.
- · STEP-1 (semaglutide, weight management, N Engl J Med 2021, PMID 33567185). Mean body weight reduction reported at 68 weeks in adults with overweight or obesity without type 2 diabetes.
- · SURPASS-2 (tirzepatide vs semaglutide head-to-head, type 2 diabetes glycaemic outcomes, N Engl J Med 2021, PMID 34170647). The only randomised head-to-head trial. Note: glycaemic endpoint in T2D, not a weight-management endpoint in obesity.
- · SELECT (semaglutide, cardiovascular outcomes in adults with overweight or obesity and established CV disease, N Engl J Med 2023, PMID 37952131). Basis for the cardiovascular outcome indication added to the semaglutide label.
Reference table: published characteristics
| Characteristic | Tirzepatide | Semaglutide |
|---|---|---|
| Active molecule | Tirzepatide | Semaglutide |
| Mechanism described in the literature | Dual GIP and GLP-1 receptor agonist | GLP-1 receptor agonist |
| UK marketing authorisation holder | Eli Lilly (brand: Mounjaro) | Novo Nordisk (brand: Wegovy) |
| Pivotal weight-management trial | SURMOUNT-1 (72 weeks) | STEP-1 (68 weeks) |
| Mean body-weight reduction reported at maximum licensed dose | Approximately 22 per cent (SURMOUNT-1) | Approximately 15 per cent (STEP-1) |
| Cardiovascular outcome indication | Not added to the UK label at time of writing | Cardiovascular outcome indication on the UK label following SELECT (in force from April 2026) |
| Half-life (SmPC) | Approximately 5 days | Approximately 7 days |
| Pen format on UK market | Pre-filled single-dose pens | Pre-filled multi-dose pen |
| NICE technology appraisal | TA1026 (tirzepatide for weight management) | TA875 (semaglutide for weight management). CV outcome indication unlocks a broader NHS reimbursement route from April 2026. |
| NHS rollout status (2026) | NHS rollout under TA1026 began June 2025 (initial cohort). Subsequent cohorts phased from 23 June 2026. | Earlier NHS approval under TA875. The April 2026 CV outcome indication broadens eligibility on the CV-prevention route. |
| Private route pricing observed in the UK market (2025+) | Reported in the £165 to £230 per month range at maintenance dosing | Reported in the £155 to £210 per month range at maintenance dosing |
Sources: SmPC entries on the MHRA Products database, NICE technology appraisal documents (TA1026, TA875), and the cited New England Journal of Medicine publications. Pricing reflects publicly listed UK private route ranges and is not a quotation.
What the head-to-head literature reports
SURPASS-2 is the only randomised head-to-head trial comparing tirzepatide and semaglutide. It was conducted in adults with type 2 diabetes and reported glycaemic and weight outcomes at 40 weeks. It is not an obesity trial. No published head-to-head randomised trial currently compares tirzepatide and semaglutide on a weight-management endpoint in adults with overweight or obesity without diabetes. The percentage-weight figures cited above come from separate placebo-controlled trials (SURMOUNT-1 and STEP-1) and are not directly comparable.
The published cardiovascular outcomes evidence is also asymmetric. SELECT reported a cardiovascular benefit for semaglutide in adults with overweight or obesity and established cardiovascular disease. No equivalent CV outcomes trial has been published for tirzepatide at the time of writing.
Adverse event profiles described in the SmPCs for both medicines are dominated by gastrointestinal events (nausea, vomiting, diarrhoea, constipation), generally most frequent during dose escalation. Refer to the current SmPC entries on the MHRA Products database for the full list and frequency tables.
UK regulatory and access framework
- · Both medicines are prescription-only (POM) under the Human Medicines Regulations 2012. They may only be supplied against a prescription written by a UK-registered prescriber.
- · The MHRA is the UK regulator that holds the marketing authorisations. Current SmPCs and patient information leaflets are published on the MHRA Products database.
- · NICE technology appraisals (TA1026 for tirzepatide, TA875 for semaglutide) set the NHS eligibility criteria. Both appraisals restrict NHS access to defined BMI thresholds, comorbidity criteria, and weight-management service settings.
- · The CMA, ASA and MHRA jointly regulate UK advertising of POM. Branded consumer-facing comparison advertising of POM is not permitted. This page is editorial commentary on the public clinical record and does not advertise any product to any individual.
- · If a UK-licensed prescriber raises one of these medicines in a consultation, the published trial reports linked above describe the evidence base they may be drawing on.
UK MHRA-licensed routes that dispense these medicines
The following directories list UK clinics and pharmacies that operate under General Pharmaceutical Council registration and CQC regulation where applicable. They are listed for reference only. Inclusion is not an endorsement of any medicine for any reader.
- · UK clinic directory: clinician-led services operating under GPhC and (where applicable) CQC oversight.
- · UK pharmacy directory: GPhC-registered online pharmacies operating under the Human Medicines Regulations 2012.
- · NHS access notes: editorial summary of the NICE-defined NHS pathway.
This page is editorial commentary on the published clinical literature and the UK regulatory record. It is not medical advice and it does not recommend any medicine to any individual. Tirzepatide and semaglutide are prescription-only medicines. The decision about whether either medicine is appropriate, and at what dose, is between a patient and a UK-licensed prescriber, who will refer to the current SmPC, the patient's clinical history, and the relevant NICE appraisal. Always read the patient information leaflet supplied with any prescribed medicine.