The CagriSema vs Mounjaro question became one of the most discussed in obesity medicine on 23 February 2026, when Novo Nordisk announced the topline results of REDEFINE-4 — the first head-to-head trial directly comparing CagriSema with tirzepatide. The result was decisive: Mounjaro at 15mg produced 23.6% average weight loss versus CagriSema’s 20.2% over 84 weeks. CagriSema failed to demonstrate non-inferiority to tirzepatide — its primary endpoint. Novo Nordisk’s share price fell 15% on the announcement. But the story is considerably more nuanced than a simple winner and loser — and for UK patients choosing between currently available options, understanding exactly what the CagriSema vs Mounjaro data means in practice is essential.

This guide covers the complete CagriSema vs Mounjaro picture — all Phase 3 trial data, the REDEFINE-4 head-to-head, mechanism differences, side effect profiles, UK availability, and who each medication suits best. Data is drawn from official Novo Nordisk and Eli Lilly announcements and the NHS obesity treatment guidance.

Last updated: 15 June 2026

REDEFINE-4 topline results announced 23 February 2026. Full peer-reviewed publication pending. REDEFINE-1 published in NEJM June 2025. This article reflects all publicly available data as of June 2026.

What is CagriSema?

CagriSema vs Mounjaro 2026 comparison REDEFINE-4 weight loss results UK Mymetabolism guide
CagriSema vs Mounjaro — REDEFINE-4 produced the first direct head-to-head comparison of these two leading next-generation weight loss medications.

CagriSema is an investigational once-weekly injectable developed by Novo Nordisk — the company that makes Ozempic and Wegovy. It combines two active ingredients: semaglutide (the same GLP-1 receptor agonist in Ozempic and Wegovy, at 2.4mg) and cagrilintide (a synthetic analogue of amylin, a pancreatic hormone that regulates blood sugar, appetite, and gastric emptying). This combination produces more weight loss than semaglutide alone — adding the amylin mechanism on top of GLP-1 receptor activation creates a more comprehensive appetite and metabolic intervention than Wegovy delivers independently.

In the CagriSema vs Mounjaro context, CagriSema represents Novo Nordisk’s attempt to close the weight loss gap with tirzepatide — which has outperformed semaglutide in every head-to-head comparison since SURPASS-2 in 2021. The REDEFINE-1 Phase 3 trial published in the New England Journal of Medicine in June 2025 showed 22.7% average weight loss at 68 weeks — higher than Wegovy 2.4mg (14.9%) and comparable to, though ultimately below, Mounjaro’s 20.9%.

Mechanism — how CagriSema and Mounjaro differ

The fundamental distinction in the CagriSema vs Mounjaro comparison is mechanism — both produce significant weight loss but through different combinations of hormonal pathways:

  • Mounjaro (tirzepatide): dual GIP and GLP-1 receptor agonist. GIP enhances insulin secretion and amplifies GLP-1’s appetite-reducing effect through a synergistic mechanism that produces substantially more weight loss than GLP-1 alone
  • CagriSema: GLP-1 receptor agonist (semaglutide 2.4mg) plus amylin receptor agonist (cagrilintide 2.4mg). Amylin slows gastric emptying, reduces glucagon secretion, and reduces appetite through pathways independent of GLP-1 — producing additive weight loss beyond semaglutide alone

Both approaches add a second mechanism to GLP-1 — Mounjaro adds GIP, CagriSema adds amylin. The REDEFINE-4 data suggests the GIP addition (tirzepatide) produces somewhat greater weight loss than the amylin addition (CagriSema) — but crucially, these are different mechanisms that may produce different tolerability profiles, and patients who do not tolerate tirzepatide may respond differently to CagriSema.

REDEFINE-4 — the head-to-head result

REDEFINE-4 was an open-label, randomised Phase 3 trial enrolling 809 adults with obesity (mean BMI approximately 38 kg/m², mean baseline weight 114.2 kg). Participants received either CagriSema 2.4mg/2.4mg weekly or tirzepatide 15mg weekly for 84 weeks. The primary endpoint was non-inferiority — demonstrating that CagriSema was at least as effective as tirzepatide.

CagriSema vs Mounjaro REDEFINE-4 results (84 weeks): CagriSema produced 20.2% average weight loss; tirzepatide produced 23.6% average weight loss. The trial did not meet its non-inferiority endpoint — CagriSema was statistically shown to produce less weight loss than tirzepatide. Novo Nordisk’s share price fell 15% on the announcement as market expectations had been higher for CagriSema’s performance.

Important context

Both 20.2% and 23.6% represent extraordinary weight loss — well above anything achievable with previous medications or lifestyle intervention alone. The CagriSema vs Mounjaro comparison is a comparison between two highly effective medications, not between an effective and ineffective one. The question for patients is not whether CagriSema works — it clearly does — but whether the difference in weight loss magnitude matters for their specific situation.

Complete weight loss data comparison

Medication Trial Duration Average weight loss Notes
Wegovy 2.4mg (semaglutide)STEP-168 weeks14.9%Licensed UK — benchmark comparator
Wegovy HD 7.2mgSTEP-768 weeks20.7%MHRA approved Jan 2026
Mounjaro 15mg (tirzepatide)SURMOUNT-172 weeks20.9%MHRA licensed — available UK
CagriSema 2.4/2.4mgREDEFINE-1 (NEJM Jun 2025)68 weeks22.7%Investigational — FDA NDA Dec 2025
CagriSema vs Mounjaro (head-to-head)REDEFINE-4 (Feb 2026)84 weeks20.2% vs 23.6%Mounjaro superior — non-inferiority not met
Retatrutide 12mgTRIUMPH-1 (May 2026)80 weeks28.3%Most effective — not yet approved

Side effects — CagriSema vs Mounjaro

In the CagriSema vs Mounjaro REDEFINE-4 trial, both medications showed gastrointestinal side effect profiles consistent with the GLP-1 medication class:

  • CagriSema: nausea, vomiting, diarrhoea, and constipation — predominantly during dose escalation. The amylin component (cagrilintide) also slows gastric emptying, which can compound nausea. Injection site reactions were reported. Overall GI tolerability was broadly comparable to semaglutide alone
  • Mounjaro: similar GI profile — nausea (most common), vomiting, diarrhoea, and constipation. The dual GIP/GLP-1 mechanism means dose escalation side effects can be pronounced. Approximately 5% of patients in SURMOUNT-1 discontinued due to adverse events
  • REDEFINE-4 discontinuation rates: 11.3% for CagriSema versus tirzepatide discontinuations not yet fully published in peer-reviewed form. This is a key outstanding data point for the CagriSema vs Mounjaro tolerability comparison

An important nuance: some patients who experience intolerable side effects on tirzepatide may tolerate CagriSema better, and vice versa — the different mechanisms produce different physiological profiles that individual patients respond to differently. Mechanism difference matters for tolerability as well as efficacy.

UK availability in 2026

The most practically important aspect of the CagriSema vs Mounjaro comparison for UK patients is availability:

  • Mounjaro: MHRA licensed since November 2023. NICE TA1026 published December 2024. NHS commissioning began June 2025. Available via private prescription from UK online pharmacies. Widely available now
  • CagriSema: not MHRA approved as of June 2026. Novo Nordisk submitted FDA NDA in December 2025, with a decision expected in late 2026. MHRA review would follow, meaning UK regulatory approval is likely in 2027 at the earliest. Available from Mymetabolism as a research peptide

In practical terms: if you want the licensed, fully approved option, Mounjaro is the clear answer in 2026. If you want to access CagriSema ahead of regulatory approval, it is available from Mymetabolism with HPLC-verified purity. See our complete CagriReta/CagriSema guide and our full product range.

Who does each medication suit?

Based on the available evidence, here is a practical guide to which side of the CagriSema vs Mounjaro comparison is most relevant for different patients:

Patient profile Better option Reason
Wants maximum licensed weight lossMounjaroMHRA approved, 20.9% average — superior in REDEFINE-4
Has not responded well to tirzepatideCagriSemaDifferent mechanism — amylin vs GIP pathway
Needs type 2 diabetes treatment alongside weight lossMounjaroLicensed for both — extensive T2D data from SURPASS programme
Responds well to semaglutide but wants more weight lossCagriSemaBuilds on semaglutide with amylin addition — familiar GLP-1 base
Wants the most powerful option availableRetatrutide28.3% — TRIUMPH-1 May 2026 — available from Mymetabolism
UK patient wanting approved treatment nowMounjaroFully licensed and widely available in UK

Browse our full product range including Mounjaro, CagriReta, and Retatrutide, and read our verified customer reviews. For the complete GLP-1 landscape comparison, see our GLP-1 medications UK guide.

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Written by the Mymetabolism Team UK-based weight management experts · Verified GLP-1 supplier · 2,400+ customers served

Common questions — CagriSema vs Mounjaro

In the REDEFINE-4 head-to-head trial, Mounjaro produced greater weight loss — 23.6% versus CagriSema’s 20.2% over 84 weeks. CagriSema failed to meet its non-inferiority endpoint. Both produced over 20% weight loss, but Mounjaro was superior on the primary outcome. For patients who don’t tolerate tirzepatide, CagriSema’s different mechanism may be a better fit.
CagriSema is an investigational once-weekly injection from Novo Nordisk combining semaglutide (GLP-1 agonist, same as Ozempic/Wegovy) with cagrilintide (amylin analogue). REDEFINE-1 showed 22.7% average weight loss at 68 weeks — higher than standard Wegovy 2.4mg but below Mounjaro in the direct comparison.
CagriSema is not yet MHRA approved. FDA NDA was submitted December 2025 with a decision expected late 2026. MHRA review would follow, meaning UK regulatory approval is likely 2027 at earliest. It is currently available from Mymetabolism as a research peptide.
CagriSema significantly outperforms standard Wegovy 2.4mg — 22.7% vs 14.9% in Phase 3 trials. Against the new high-dose Wegovy HD 7.2mg, the gap narrows to 22.7% vs 20.7%. CagriSema’s amylin addition produces meaningful extra weight loss beyond semaglutide alone.
Primarily gastrointestinal — nausea, vomiting, diarrhoea, and constipation — consistent with GLP-1 medications. Most prominent during dose escalation. The amylin component adds additional gastric slowing, which can compound nausea in some patients. Side effects reduce significantly as the body adapts.

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