What the human research shows
The rare investigational compound with two large, published phase 3 trials — so the weight-loss row is graded A on certainty even though the product is not approved. The number disappointed the market (Novo had guided to 25%) but is the best published result for any combination, and about seven points above semaglutide alone in the same trial.
Evidence profile0–5
- Metabolic & weightA5.0
- Cardiovascular—0.0
- Muscle & growth—0.0
- Healing & repair—0.0
- Neuro & sleep—0.0
- Immune & inflammation—0.0
- Sexual & hormonal—0.0
- Skin & appearance—0.0
- Ageing & longevity—0.0
| Outcome | Grade | Effect size | Human studies | Where the evidence comes from |
|---|---|---|---|---|
| Body weight (obesity without diabetes) | AEstablished | Large | 1 phase 3 RCT (n=3,417, 68 wk) | REDEFINE 1 randomised 2,108 people to the combination, 302 to semaglutide alone, 302 to cagrilintide alone and 705 to placebo. The combination lost 20.4% against 3.0% on placebo; the single agents landed in between. Published in the New England Journal of Medicine.1 |
| Body weight (obesity with type 2 diabetes) | AEstablished | Large | 1 phase 3 RCT (n=1,206, 68 wk) | REDEFINE 2: 13.7% loss against 3.4% on placebo — the usual smaller effect in people with diabetes. Nearly three-quarters reached an HbA1c of 6.5% or below.2 |
| Blood glucose (HbA1c) in type 2 diabetes | AEstablished | Large | 1 phase 3 RCT (n=1,206) | In REDEFINE 2, 73.5% of people on the combination reached an HbA1c of 6.5% or less against 15.9% on placebo.2 |
| Body weight (vs tirzepatide 5 mg, type 2 diabetes) | BProbable | Moderate | 1 phase 3 RCT topline (REIMAGINE 5, 60 wk) | Novo Nordisk press release, 21 September 2026: in adults with type 2 diabetes not controlled on metformin, an SGLT2 inhibitor or both, CagriSema 1.0 mg/1.0 mg produced 12.4% weight loss at 60 weeks against 9.1% on tirzepatide 5 mg, with HbA1c reductions of 1.71 and 1.67 points (non-inferior). Both arms were low doses: tirzepatide's lowest maintenance dose, and less than half the 2.4 mg/2.4 mg of CagriSema used in REDEFINE 1. Efficacy estimand; enrolment not stated; not peer-reviewed, so B. The same release reports 21.0% against 2.0% on placebo at 68 weeks for the 1.0 mg/1.0 mg dose in obesity (REDEFINE 9).3 |
| GI side effectsadverse | AEstablished | Large | Both phase 3 RCTs | Four in five people on the combination had gastrointestinal events in REDEFINE 1, against two in five on placebo; the same pattern in REDEFINE 2 (72.5% vs 34.4%). Mostly transient and mild to moderate, as with the parent drugs.12 |
Literature searched to 7 October 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.
Registered trials
ClinicalTrials.gov lists 10 interventional studies naming CagriSema as an intervention — 3 completed, 3 recruiting, and none with results posted to the registry.
A registration is not a result. Anyone can register a study, and many never report — so this list shows what has been attempted, not what has been shown. The graded evidence above is the answer to whether something works.
2 further studies are registered. Participant counts marked * are the sponsor's estimate, not a final enrolment. Source: ClinicalTrials.gov, read directly from the registry and refreshed weekly.
What it is
CagriSema is not a new molecule but a fixed pairing: cagrilintide, Novo Nordisk's long-acting analogue of the pancreatic hormone amylin, injected together with semaglutide at its full obesity dose. The idea is that amylin and GLP-1 suppress appetite through different pathways and add up.
It is the most advanced amylin-based obesity treatment. The REDEFINE programme has read out in obesity and in type 2 diabetes, and a cardiovascular-outcomes trial is running. Amycretin, also from Novo, does the same two jobs in a single peptide and is a stage behind.
How it is thought to work
Semaglutide slows stomach emptying and reduces appetite through GLP-1 receptors in gut and brain. Cagrilintide activates amylin receptors in the hindbrain, which signal fullness after a meal. Together they reduced weight by about seven percentage points more than semaglutide alone in REDEFINE 1, though the semaglutide-alone arm was small.
What is still unknown
- Whether the combination protects the heart beyond what semaglutide already does; the outcomes trial has not reported.
- Head-to-head against full-dose tirzepatide in obesity: REDEFINE 4 is running, unreported at review. REIMAGINE 5 compared low doses of each in type 2 diabetes.
- Why the result fell short of the 25% the phase 2 suggested — trial conduct, dose escalation and adherence have all been proposed.
The molecule and how long it lasts
A co-formulation of two molecules: see cagrilintide and semaglutide
- Route
- Subcutaneous, once weekly (two injections)
- Half-life
- A combination: cagrilintide about 7–8 days, semaglutide about 1 week
From a published human pharmacokinetic study: Enebo LB, et al. Lancet 2021 (cagrilintide with semaglutide 2.4 mg, phase 1b)
Regulatory status
Investigational; no EMA authorisation at review.
Novo Nordisk filed a New Drug Application for weight management in December 2025 and says it expects an FDA decision in the fourth quarter of 2026. Not approved at review; products sold under the name are not the trial drug.
No MHRA licence.
Investigational only.
No Drug Identification Number.
Cagrilintide is unapproved, so the combination falls under S0 (non-approved substances) even though semaglutide is not banned.
Questions people actually ask
How much weight do people lose on CagriSema?
Is CagriSema better than tirzepatide?
Is CagriSema available?
Why did the result disappoint?
One page per claimed effect
- ADoes CagriSema help with body weight?1 phase 3 RCT (n=3,417, 68 wk)
- ADoes CagriSema help with body weight?1 phase 3 RCT (n=1,206, 68 wk)
- ADoes CagriSema help with blood glucosein type 2 diabetes?1 phase 3 RCT (n=1,206)
- BDoes CagriSema help with body weight?1 phase 3 RCT topline (REIMAGINE 5, 60 wk)
- AHow common is GI side effects with CagriSema?Both phase 3 RCTs
References
- 1Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).N Engl J Med, 20253,417 randomised, 68 weeks. NCT05567796.
- 2Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).N Engl J Med, 20251,206 randomised, 68 weeks. NCT05394519.
- 3Novo Nordisk. CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (with REDEFINE 9 topline).Press release, 21 Sep 2026REIMAGINE 5: 60 weeks, type 2 diabetes, vs tirzepatide 5 mg. REDEFINE 9: 68 weeks, obesity, vs placebo. Topline, efficacy estimand; not peer-reviewed. States the US filing of December 2025 and a decision expected in Q4 2026.
Change log
- 2026-10-07REIMAGINE 5 and REDEFINE 9 topline results (press release, 21 Sep 2026) added as a new row against tirzepatide 5 mg, graded B; US filing status updated (filed December 2025, decision expected Q4 2026). Overall grade unchanged.
- 2026-09-23Initial publication from the two published REDEFINE phase 3 trials. Overall grade B (investigational, unapproved); the trial rows are graded A on their own certainty.