The REDEFINE 4 results
REDEFINE 4 is the only completed trial that compared CagriSema directly with Mounjaro.
It enrolled 809 adults living with obesity, ran for 84 weeks, and was open-label (participants and clinicians knew which drug they were on).1
The trial was designed to test whether CagriSema was at least as effective as Mounjaro 15 mg, within a pre-specified margin. Novo Nordisk wasn’t trying to prove CagriSema was better; just that it matched.
That main goal wasn’t met.
Among those who took the drug as prescribed (the on-treatment figure), CagriSema produced an average weight loss of 23.0% versus 25.5% for Mounjaro 15 mg.1
Counting everyone who started the trial, including those who stopped (the treatment-policy figure), the comparison was 20.2% for CagriSema versus 23.6% for Mounjaro.1
Both figures represent substantial weight loss. Mounjaro 15 mg produced more in this trial.
REDEFINE 4 was announced via Novo Nordisk’s press release on 23 February 2026. It hasn’t yet been peer-reviewed. The figures are accurate, but the full analysis is still to be published.1
Part of a broader pattern
REDEFINE 4 isn’t the first trial where Mounjaro has produced more weight loss than a semaglutide-based option.
SURMOUNT-5, published in 2025, compared Mounjaro 15 mg directly with Wegovy 2.4 mg in adults living with obesity.
Over 72 weeks, Mounjaro produced an average weight loss of 20.2% versus 13.7% for Wegovy.7
CagriSema combines cagrilintide with semaglutide, producing more weight loss than semaglutide alone. REDEFINE 4 showed it still produces less than Mounjaro.
How they work: GIP vs amylin
Both drugs mimic two hormones, but each pairs GLP-1 with a different second hormone: Mounjaro with GIP, CagriSema with amylin.
Mounjaro contains a single drug called tirzepatide. It’s a dual agonist, meaning one molecule mimics two hormones at once: GLP-1 and GIP.
Both hormones are involved in managing appetite and blood sugar control.
CagriSema is a combination of two drugs in one once-a-week injection: cagrilintide (a long-acting form of amylin) and semaglutide.
Semaglutide is the same drug used in Wegovy and Ozempic. It mimics GLP-1, a hormone our gut releases after we eat.
Semaglutide slows the rate at which our stomach empties, reduces glucagon levels, enhances insulin release, and communicates with the appetite centres in the brain.
Cagrilintide mimics amylin, a hormone our pancreas releases alongside insulin. It works in a different part of the brain, prolonging the feeling of fullness after eating.
In trials directly comparing them, GIP combinations have produced more weight loss than semaglutide-based options.
Mounjaro led to more weight loss than Wegovy (semaglutide alone) in SURMOUNT-5 and CagriSema (semaglutide plus amylin) in REDEFINE 4.
The current evidence suggests that adding GIP to GLP-1 produces more weight loss than adding amylin.
Weight-loss results compared
REDEFINE 4 is the only trial to date that directly compares CagriSema and Mounjaro.
Cross-trial comparisons can give us an indication of how they compare, but different populations, baselines, and durations all affect the results.
| Drug |
Trial |
n / duration |
On-treatment |
Treatment-policy |
Peer-reviewed |
| CagriSema |
REDEFINE 12 |
3,417 / 68 weeks |
22.7% |
20.4% |
Yes (NEJM 2025) |
| CagriSema |
REDEFINE 4 (vs Mounjaro)1 |
809 / 84 weeks |
23.0% |
20.2% |
No (press release) |
| Mounjaro 15 mg |
SURMOUNT-13 |
2,539 / 72 weeks |
22.5% |
20.9% |
Yes (NEJM 2022) |
| Mounjaro 15 mg |
REDEFINE 4 (vs CagriSema)1 |
809 / 84 weeks |
25.5% |
23.6% |
No (press release) |
In their separate obesity-only trials, the figures look very similar.
CagriSema produced 22.7% weight loss in REDEFINE 1, and Mounjaro 15 mg produced 22.5% in SURMOUNT-1.2,3
On a cross-trial basis, the two drugs seem to produce similar results.
In REDEFINE 4, Mounjaro 15 mg produced about 2.5 percentage points more weight loss than CagriSema on the on-treatment figure, and about 3.4 percentage points more on the treatment-policy figure.1
Mounjaro 15 mg also produced slightly more weight loss in REDEFINE 4 (25.5%) than in SURMOUNT-1 (22.5%), likely reflecting the longer 84-week duration and differences in trial populations.1,3
A note on the maximum dose
A higher-dose CagriSema trial (REDEFINE 11) is running in parallel, with results expected in the first half of 2027.
The higher dose will test whether CagriSema can produce more weight loss than the 22.7% seen at the standard dose.
Effects on blood sugar
Mounjaro is licensed in the UK for both managing obesity and treating type 2 diabetes. The same drug is used at different doses for both.
CagriSema’s REDEFINE 2 trial tested it specifically in adults living with type 2 diabetes and obesity.
Over 68 weeks, CagriSema produced an average weight loss of 15.7% alongside an HbA1c reduction of 1.8 percentage points.8
HbA1c is a measure of average blood glucose over the previous two to three months.
Mounjaro produces similar glucose-lowering effects and is the current first-line GLP-1 medication for people living with both type 2 diabetes and obesity in the UK.
The two drugs haven’t been directly compared in adults living with type 2 diabetes. Still, based on the available evidence, Mounjaro seems to lead to lower blood sugar levels than CagriSema.
Side effects and tolerability
Both drugs are GLP-1 medications, and both produce a similar pattern of side effects. Most are gastrointestinal.
In REDEFINE 1, 79.6% of people on CagriSema reported at least one gastrointestinal side effect, versus 39.9% on placebo.2 Nausea affected approximately 55%, constipation 30.7%, and vomiting 26.1%.2
Mounjaro’s side effect profile is very similar. In SURMOUNT-1, gastrointestinal side effects were the most common, mostly mild to moderate.3
REDEFINE 4 reported gastrointestinal side effects as the most frequent on both drugs.1
Detailed per-drug breakdowns aren’t yet available because the full results haven’t been published.
For most people, the side-effect profiles look broadly comparable. If GI side effects on Mounjaro are the reason you’re considering a switch, CagriSema may not solve that.
How many people stopped because of side effects
In REDEFINE 1, 5.9% of participants stopped CagriSema because of side effects.
In SURMOUNT-1, the number of participants who stopped taking Mounjaro was broadly similar at the licensed doses.2,3
Reaching the maximum dose
Only 57% of the CagriSema group in REDEFINE 1 reached the full 2.4/2.4 mg maintenance dose during the build-up period.2 The rest stayed on lower doses, usually because of side effects.
This isn’t unique to CagriSema. A meaningful share of people on Mounjaro also stay below the maximum 15 mg dose because of tolerability.
Body composition
Both drugs cause some lean mass loss (mainly muscle) alongside fat loss.
In GLP-1 trials, roughly 20-25% of total weight loss is lean mass rather than fat.
Losing too much muscle mass slows resting metabolism, reduces strength and physical function, and increases the likelihood of weight regain after stopping the medication.
This is why resistance training and adequate protein intake are recommended alongside any GLP-1 medication, regardless of which drug.
UK availability and cost
The clearest difference between the two drugs in May 2026 is availability.
Mounjaro is licensed and prescribed in the UK. CagriSema isn’t.
Mounjaro
The MHRA licensed Mounjaro for obesity in November 2023. NICE published technology appraisal TA1026 in December 2024, recommending it for adults who meet specified criteria.4
NHS commissioning began on 23 June 2025. NHS eligibility is strict: a body mass index (BMI, a measure of weight relative to height) of 40 or above, plus four of five specified weight-related health conditions, plus enrolment in a specialist support programme.4
Outside the NHS, Mounjaro is widely available through registered UK online pharmacies via private prescription. Private monthly costs typically range from £150 to £375+, depending on dose and provider.
CagriSema
CagriSema is investigational. Novo Nordisk submitted a New Drug Application to the U.S. Food and Drug Administration on 18 December 2025, with a U.S. regulatory decision expected in late 2026.
There’s no public confirmation of an MHRA submission in the UK.
Based on the Wegovy and Mounjaro pattern, a realistic UK private launch would be late 2026 to 2027 if Novo Nordisk submits this year.
NHS availability would follow separately, via a NICE technology appraisal, typically 13 to 18 months after MHRA approval.
Novo Nordisk hasn’t announced UK pricing for CagriSema. Until that’s published, any figures circulating online are speculation.
For now, only Mounjaro is a real option in the UK from this comparison.
Should you consider switching?
If you’re on Mounjaro and it’s working well
The data from REDEFINE 4 doesn’t support switching.
Mounjaro produced more weight loss than CagriSema, so the evidence-based action is to stay with what’s working.1
If you’re on Mounjaro and tolerating it poorly
The broadly comparable side-effect profile means CagriSema may not solve that.
Speak to your prescriber first about dose adjustment, slower titration, or anti-nausea support.
If you’re not yet on either drug
Only Mounjaro is licensed and available in the UK. You can ask your GP about Mounjaro on the NHS, or explore private prescribing routes if you don’t meet NHS eligibility.
A note on stopping
Weight loss on GLP-1 medications is sustained while the medication is being taken.
When people stop, most regain a significant proportion of the weight lost. This applies to both drugs and other GLP-1 medications.
Emerging research suggests that people who come off the medication gradually, with structured habit-change support, are more likely to maintain their weight loss.
Frequently asked questions
Is CagriSema more effective than Mounjaro?
No, based on the only direct comparison published so far.
In REDEFINE 4, CagriSema produced an average weight loss of 23.0% versus 25.5% for Mounjaro 15 mg over 84 weeks.1
The trial was designed to test whether CagriSema was at least as effective as Mounjaro. That main goal wasn’t met.1
Should I switch from Mounjaro to CagriSema?
Not based on current evidence, and not least because CagriSema isn’t available in the UK yet.
If Mounjaro is working well, the data from REDEFINE 4 supports staying on it.
If you’re tolerating it poorly, speak to your prescriber about dose adjustment first.
Why didn’t CagriSema beat Mounjaro?
The most likely explanation is in how the drugs work.
Mimicking the hormone GIP (what Mounjaro does) appears to add more weight loss than mimicking amylin (what CagriSema does), alongside GLP-1.
Mounjaro has produced greater weight loss in two large trials directly comparing it with semaglutide-based options: SURMOUNT-5 (20.2% vs 13.7%) and REDEFINE 4 (25.5% vs 23.0%).1,7
Other possible factors include the relative doses tested (Mounjaro at its maximum of 15 mg versus CagriSema at 2.4/2.4 mg), trial-specific factors, and the fact that the full REDEFINE 4 analysis hasn’t yet been published.
Which has fewer side effects, CagriSema or Mounjaro?
The side-effect profiles look broadly comparable. Both produce gastrointestinal side effects as the most common, and both are GLP-1 medications.1,2,3
REDEFINE 4 hasn’t yet published per-drug side-effect data, so a precise comparison isn’t possible.1
Will CagriSema be cheaper than Mounjaro in the UK?
We don’t know. Novo Nordisk hasn’t announced UK pricing for CagriSema.
Mounjaro currently costs £150 to £375+ per month privately in the UK, depending on dose and provider. CagriSema will likely launch at a similar level or slightly higher.
Can I get CagriSema in the UK now?
No. CagriSema isn’t approved by the MHRA and isn’t available through any UK route, NHS or private.
Is CagriSema available on the NHS?
No. NHS availability requires both an MHRA licence and a NICE technology appraisal. Neither has happened for CagriSema.
Based on the Wegovy and Mounjaro pattern, NHS availability is likely 13 to 18 months or more after MHRA approval, whenever that happens.4,5
What’s the difference between cagrilintide and tirzepatide?
Tirzepatide is the drug in Mounjaro. It’s a single molecule that mimics two hormones (GLP-1 and GIP).
Cagrilintide is a long-acting form of amylin, used alongside semaglutide in CagriSema. They mimic different hormones that help to manage hunger.
Are CagriSema and Mounjaro the same type of drug?
Both are injectable weight-loss medications that work by mimicking gut hormones. But they’re not the same drug, and the hormones they mimic are different.
Mounjaro is a GLP-1/GIP dual agonist. CagriSema is a GLP-1 plus amylin combination.
Take home message
Mounjaro has produced more weight loss than CagriSema in the only direct comparison trial.
REDEFINE 4 reported an average weight loss of 25.5% for Mounjaro 15 mg versus 23.0% for CagriSema over 84 weeks.1
In SURMOUNT-5, Mounjaro also produced more weight loss than Wegovy (20.2% vs 13.7% over 72 weeks). The pattern suggests that adding GIP to GLP-1 yields greater weight loss than adding amylin.7
Side-effect profiles look broadly comparable, with gastrointestinal side effects most common on both drugs.
Detailed per-drug data from REDEFINE 4 hasn’t been published yet.1
In the UK, only Mounjaro is licensed and available. CagriSema is investigational and isn’t a near-term option here.
A UK private launch is plausible in late 2026 to 2027 at the earliest, with NHS availability likely some time later.
REDEFINE 4 is a press-release report, not yet a peer-reviewed paper. The full analysis hasn’t been published.
Second Nature’s Mounjaro programme combines the medication with personalised nutrition guidance from registered dietitians and nutritionists, built around a balanced plate of half vegetables, a quarter protein, a quarter complex carbohydrates, plus a serving of fat.
A peer-reviewed study published in JMIR Formative Research found that active subscribers on Second Nature’s semaglutide-supported programme lost an average of 19.1% of their body weight at 12 months, with 77.7% achieving at least 10% weight loss.6
For more on how CagriSema works, the trials, and the likely UK timeline, see our CagriSema overview guide. For the latest on UK availability, see our CagriSema UK availability article.
Second Nature's Mounjaro and Wegovy programmes
Second Nature provides Mounjaro or Wegovy as part of our Mounjaro and Wegovy weight-loss programmes.
Why choose Second Nature over other medication providers, assuming you're eligible?
Because peace of mind matters.
We've had the privilege of working with the NHS for over eight years, helping people across the UK take meaningful steps toward a healthier, happier life.
Our programmes are designed to meet people where they are, whether that means support with weight loss through compassionate one-to-one health coaching, or access to the latest weight-loss medications (like Mounjaro and Wegovy) delivered alongside expert care from a multidisciplinary team of doctors, psychologists, dietitians, and personal trainers.
At the heart of everything we do is a simple belief: real, lasting change comes from building better habits, not relying on quick fixes. We're here to support that change every step of the way.
With over a decade of experience, thousands of lives changed, and a long-standing record of delivering programmes used by the NHS, we believe we're the UK's most trusted weight-loss programme.
We hope to offer you something invaluable: peace of mind, and the support you need to take that first step.
References
- Novo Nordisk. (2026). CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity; the primary endpoint was not achieved. Press release, 23 February 2026.
- Garvey, W.T. et al. (2025). Coadministered cagrilintide and semaglutide in adults with overweight or obesity. New England Journal of Medicine, 393(7), 635-647.
- Jastreboff, A.M. et al. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387, 205-216.
- NICE. (2024). Tirzepatide for managing overweight and obesity. Technology Appraisal TA1026.
- NICE. (2023). Semaglutide for managing overweight and obesity. Technology Appraisal TA875.
- Richards, R. et al. (2025). A Remotely Delivered GLP-1RA-Supported Specialist Weight Management Program in Adults Living With Obesity: Retrospective Service Evaluation. JMIR Formative Research, 9(1), e72577.
- Aronne, L.J. et al. (2025). Tirzepatide as compared with semaglutide for the treatment of obesity. New England Journal of Medicine.
- Davies, M.J. et al. (2025). Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes. New England Journal of Medicine, 393(7), 648-659.
