What did the SURPASS study programme find about tirzepatide?

What is the SURPASS programme and why does it matter for UK patients?

SURPASS stands for the phase 3 clinical programme that Eli Lilly ran to evaluate tirzepatide before it could be licensed. The trials covered type 2 diabetes management (that is the core SURPASS series) and a parallel obesity programme called SURMOUNT. Together they provide the evidence that regulators, including the MHRA and NICE, relied on when reviewing tirzepatide. NICE published its appraisal of tirzepatide for weight management in December 2024 (TA1026), concluding that the medicine is recommended within specific eligibility criteria, and the UK licence reflects both the diabetes and weight-management indications.

What makes the programme distinctive is its breadth. Rather than a single pivotal trial, the SURPASS design tested tirzepatide head-to-head against semaglutide (SURPASS-2), against insulin degludec (SURPASS-3), against basal insulin combinations, and in people with cardiovascular disease. This gives clinicians a richer picture than most new medicines arrive with. For patients, it means the prescribing decisions made today draw on direct comparisons, not just placebo data. You can read more about the tirzepatide evidence base on our tirzepatide overview page.

The SURPASS trials enrolled participants with type 2 diabetes; the weight-loss data most relevant to UK adults without diabetes comes from the SURMOUNT arm. Both sets of results fed into the regulatory files submitted to the MHRA and the European Medicines Agency.

What did the individual SURPASS trials each set out to test?

SURPASS-1 compared tirzepatide at 5mg, 10mg and 15mg against placebo in adults with type 2 diabetes whose blood sugar was not controlled by diet and exercise alone, no background glucose-lowering medicine. Across 40 weeks, all three doses reduced HbA1c significantly more than placebo, and the 10mg and 15mg doses achieved average HbA1c reductions of around 2.0–2.1 percentage points. A notable proportion of participants in the higher-dose arms reached normal blood-sugar ranges.

SURPASS-2 is arguably the most cited trial in clinical conversations because it ran tirzepatide directly against semaglutide 1mg (Ozempic) in adults already on metformin. At all three doses, tirzepatide reduced HbA1c and body weight more than semaglutide 1mg over 40 weeks. The SURPASS-2 trial results page covers those findings in detail.

SURPASS-3 tested tirzepatide against insulin degludec in insulin-naive adults on oral agents. SURPASS-4 enrolled a higher-risk group (people with type 2 diabetes and cardiovascular disease) and compared tirzepatide to glargine insulin over 104 weeks. SURPASS-5 added tirzepatide on top of existing insulin glargine therapy. The consistent pattern across all arms: higher doses produced greater improvements in both glycaemic control and weight, with a manageable GI side-effect profile. For a summary of how the trials fit together as a programme, the SURPASS trial overview is a useful starting point.

How do SURPASS results translate to what is licensed for weight management in the UK?

The SURPASS diabetes trials established the safety and efficacy profile; the SURMOUNT trials then extended that evidence to adults with obesity who did not have type 2 diabetes. SURMOUNT-1, the flagship obesity study, randomised 2,539 adults and reported average body-weight reduction of around 20–21% at 15mg over 72 weeks, figures that informed NICE's recommendation. A later head-to-head study, SURMOUNT-5, compared tirzepatide directly to semaglutide 2.4mg and found greater average weight reduction with tirzepatide, as the SURMOUNT-1 results page covers alongside the pivotal diabetes findings.

In the UK, Mounjaro (tirzepatide) is licensed for weight management in adults with a BMI of 30 or above, or 27 and above alongside at least one weight-related condition such as high blood pressure or obstructive sleep apnoea. NICE's appraisal TA1026 sets the NHS eligibility criteria at BMI 35 or above with at least one qualifying comorbidity; private prescribing follows the licensed criteria, which are broader. The NHS tirzepatide patient page on the NHS website covers what the medicine is, how it works and what to expect.

Treatment in all the trials started at a low dose (the 2.5mg starting dose exists to give the body time to adjust before stepping up) and titration happened in approximately four-week steps. That same schedule applies in clinical practice; the exact path for any individual is decided by their prescriber.

What are the side-effect patterns the SURPASS trials reported, and what should patients know?

Across the SURPASS programme, the most common side effects were gastrointestinal: nausea, diarrhoea, vomiting and constipation appeared most often at the point of starting treatment or stepping up a dose, then tended to settle over days to a couple of weeks. The pattern is well-established enough that prescribers factor it into titration planning. Injection-site reactions and reduced appetite were also reported. Severe events were uncommon but include acute pancreatitis, a known risk with GLP-1 class medicines. Persistent, severe stomach pain that extends to the back warrants prompt medical attention.

The trials also tracked cardiovascular and renal outcomes. In the diabetes programme, tirzepatide did not increase cardiovascular risk at the doses studied, and weight reduction of the scale observed in SURMOUNT-1 carries its own secondary cardiovascular benefits, though Mounjaro's UK licence for weight management does not carry a specific cardiovascular outcome claim as of mid-2026.

One question our prescribers hear regularly is whether the trial results reflect real-world use. Trials are conducted under controlled conditions with structured follow-up, real-world outcomes vary by adherence, lifestyle factors and individual biology. If you are weighing up whether tirzepatide might be suitable for you, our Mounjaro guide sets out the full clinical picture, and the cost context for private treatment is covered on our Mounjaro cost page. The right next step is a clinical conversation, not a spreadsheet of trial averages. Our prescribers review every consultation the same day, a real clinician reads your answers, not an automated queue. Check your eligibility by starting a free consultation with our team.