CagriSema
Cagrilintide + Semaglutide (Novo Nordisk)
Evidence grade 3 of 5, Mixed. Read how the Atlas grades evidence.
CagriSema rests on two large 68-week phase 3 trials, REDEFINE 1 (n=3,417, without diabetes) and REDEFINE 2 (n=1,206, with type 2 diabetes), both published in the New England Journal of Medicine in 2025. REDEFINE 1 met its primary endpoint with 22.7% mean weight reduction on the efficacy estimand (20.4% on the treatment-policy estimand) versus placebo, yet fell short of Novo Nordisk's internal ambition of 25% or greater, a gap that sent the share price sharply lower. An NDA was submitted to the FDA in December 2025 with review expected in 2026, so the combination is not yet approved; grade 3 reflects strong pivotal phase 3 data that has not reached regulatory clearance.
- FDA
- NDA submitted to FDA 18 December 2025 (REDEFINE 1 and REDEFINE 2); FDA review expected 2026; not yet approved
- WADA
- Not prohibited
Reference only. Not medical advice.
What can go wrong
Investigational and not yet approved; gastrointestinal effects typical of GLP-1/amylin agents; any US product before approval is unauthorized and unsafe.
Talk to a clinician before taking this, particularly if you have a thyroid condition. The Atlas can tell you what has been studied about CagriSema. It cannot tell you how it would interact with your body, your history, or anything else you are taking, and nothing on this page is a reason to start.
Novo Nordisk's once-weekly fixed combination of cagrilintide (amylin analogue) and semaglutide (GLP-1 agonist). Phase 3 REDEFINE 1 showed 22.7% mean weight loss, among the strongest obesity results reported, but it missed the company's own 25% ambition and sent the stock lower. An FDA NDA was filed in December 2025 with review expected in 2026; it is not yet approved.
What people take it for
These are the reasons people give for taking it. They are not effects it has been shown to have.
How it is supposed to work
CagriSema attacks appetite from two directions at once. It pairs semaglutide, the familiar GLP-1 agonist, with cagrilintide, a long-acting analog of amylin, a second satiety hormone released with insulin. The two act on overlapping brain regions that control hunger and fullness but through different receptors, so combining them was expected to suppress appetite more than either alone. In a single weekly injection it aims to decrease hunger and increase the sense of fullness more completely than a GLP-1 drug by itself, the logic being that two complementary satiety signals beat one.
CagriSema is a fixed-dose, once-weekly subcutaneous combination of cagrilintide 2.4 mg and semaglutide 2.4 mg, developed by Novo Nordisk as the first pairing of a GLP-1 receptor agonist with an amylin analog. Cagrilintide is an acylated amylin analog engineered for weekly dosing; semaglutide is the same molecule sold as Wegovy and Ozempic. The product is investigational, not yet approved in the US or EU, and is the centerpiece of Novo's effort to leapfrog the dual agonist tirzepatide with a two-hormone strategy.
- Type
- Amylin + GLP-1 combo
- Components
- Cagrilintide + semaglutide
- Dose
- 2.4 mg / 2.4 mg weekly
- REDEFINE 1
- 22.7%
- Status
- Investigational (NDA filed)
- Maker
- Novo Nordisk
The Combination That Underwhelmed
CagriSema is the clearest lesson in this library that more mechanisms do not automatically mean more benefit. Novo combined two satiety hormones expecting to clear 25% weight loss and decisively beat tirzepatide. Instead the pivotal REDEFINE 1 trial landed at 22.7%, and the market reaction was brutal: Novo's shares fell about 20% on the topline, while rivals rose. The number is genuinely strong in absolute terms and beats semaglutide alone, but it sits roughly level with tirzepatide while adding a second drug, more cost and more complexity, which is not the leap the strategy promised. A muddying detail is that only about 57% of patients reached the top dose under a flexible protocol, so the ceiling may be higher than the headline. Still, the episode reframed the field's central question: in a race now defined by magnitude, does stacking mechanisms win, or does a single powerful molecule like the triple agonist retatrutide?
Safety in detail
- Gastrointestinal effects dominate, as with all incretin therapies, and amylin adds its own nausea burden (cagrilintide alone caused nausea in about a quarter of users), so combined tolerability is a real consideration.
- The flexible dosing in REDEFINE 1, where many patients stayed on a submaximal dose, partly reflects managing side effects.
- It carries the established GLP-1 cautions inherited from semaglutide: thyroid C-cell warning, pancreatitis and gallbladder risk, and care with insulin or sulfonylureas.
- As an investigational combination, its long-term safety profile is still being established.
- It is a regulated pharmaceutical candidate, not a gray-market peptide, so the dominant risks are clinical rather than sourcing-related.
- Amylin analogs are not prohibited in sport.
Children and teenagers
CagriSema is investigational and not approved or studied in anyone under 18. The broader debate about treating adolescent obesity with incretin drugs applies to its approved component semaglutide, but not yet to the combination, which has no pediatric data. Any pediatric use would be premature until the adult program is complete and a regulator has acted; this is a clinical-development question, not a gray-market one.
What people get wrong
Nothing recorded here yet. There is almost certainly something people get wrong about this one, and the blank space means we have not written it down, not that the record is clean.
Who profits, and who pushes back
Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.
CagriSema is wholly Novo Nordisk's, strategically as much as commercially. It is the company's bid to answer Eli Lilly's tirzepatide and to extend the semaglutide franchise with a next-generation product, which is why the disappointing efficacy hit Novo's valuation so hard. Unlike the gray-market peptides in this library, there is no underground economy here: the value is concentrated in one regulated manufacturer and its future pricing, rebate and coverage decisions, the same forces that shape access to every branded obesity drug.
How we got here
CagriSema is a fixed-dose pairing of two Novo Nordisk molecules. Semaglutide is an acylated GLP-1 receptor agonist first approved as Ozempic in 2017 and later as Wegovy for weight management. Cagrilintide, originally coded AM833 / NNC0174-0833, is a long-acting amylin analogue built on a pramlintide-like 37-amino-acid backbone with fatty-acid acylation adapted from the same technology behind insulin degludec and semaglutide, engineered for once-weekly dosing to overcome pramlintide's short half-life. After phase 1b data showed the two agents gave additive weight loss, Novo Nordisk advanced them as the CagriSema combination through the phase 3 REDEFINE program, then submitted the US NDA in December 2025.
CagriSema brought together two Novo molecules: semaglutide, the company's blockbuster GLP-1 drug, and cagrilintide, a long-acting amylin analog that entered trials in the mid-2010s. The pairing was meant to extend Novo's lead in obesity and counter Lilly's tirzepatide. In December 2024 the topline REDEFINE 1 result of 22.7% fell short of the 25% the company had signaled, and Novo's stock dropped sharply. Full REDEFINE 1 and REDEFINE 2 data were published in NEJM and presented at ADA in mid-2025, Novo filed for FDA approval in December 2025, and a longer follow-on trial was launched to chase a higher number.
- Mid-2010sCagrilintide, a weekly amylin analog, enters clinical development at Novo.
- 2024REDEFINE 1 topline of 22.7% falls short of the 25% goal; Novo shares drop about 20%.
- Jun 2025Full REDEFINE 1 and 2 data published in NEJM and presented at ADA.
- Dec 2025Novo files a US New Drug Application for CagriSema.
- 2026FDA review expected; approval possible in late 2026 or early 2027.
The numbers behind the grade
- Weight loss
- 22.7%
- Components
- Sema + cagrilintide
- vs target
- Below 25% goal
- NDA filed
- Dec 2025
- FDA decision
- 2026
- Maker
- Novo Nordisk
The people taking it
Novo Nordisk's most-watched pipeline product and one of the most closely followed disappointments in obesity medicine: the combination that was supposed to beat tirzepatide and instead roughly matched it, moving markets in the process.
CagriSema's populations are defined by its trials rather than a gray market: adults with obesity, and separately adults with obesity and type 2 diabetes. If approved, its real-world demographics would resemble the broad obesity-drug population, with the same access skew toward higher-income, insured patients seen across the class. There is no meaningful self-sourcing community here, because it is a regulated combination product, not a vial sold online.
Currently used only within Novo Nordisk's trials for obesity and for type 2 diabetes; not yet marketed anywhere. If approved, it would be prescribed as a once-weekly injection for weight management. Not prohibited in sport.
Set against the alternatives
CagriSema's problem is not that it is weak but that it arrived into a field it no longer leads. Its 22.7% beats semaglutide alone (16.1%) and roughly doubles cagrilintide alone (11.8%), confirming real synergy between amylin and GLP-1. But it sits about level with tirzepatide, which is already approved and simpler, and it trails the investigational triple agonist retatrutide at 28 to 30%. So a drug designed to beat the dual agonist instead matched it while adding a second molecule. Its place is as a strong second-tier option whose value will depend on tolerability, pricing and whether longer, higher-dose trials lift the number.
| Semaglutide (Wegovy) | GLP-1 | ~16.1% (alone) | Approved |
|---|---|---|---|
| Cagrilintide | Amylin (alone) | ~11.8% | Investigational |
| CagriSema | Amylin + GLP-1 | ~22.7% | NDA filed |
| Tirzepatide (Zepbound) | GIP + GLP-1 | ~20 to 22.5% | Approved |
| Retatrutide | GIP + GLP-1 + glucagon | ~28 to 30% | Investigational |
What we do not know
- Whether the FDA approves it in 2026 and on what label.
- Whether its roughly tirzepatide-level efficacy, achieved with two drugs, supports strong uptake.
- Whether the longer, higher-dose REDEFINE 11 trial lifts the weight-loss number.
- How its tolerability and pricing compare with simpler single-agent options.
- Whether single-molecule successors like amycretin or the triple agonist retatrutide make two-drug combinations less compelling.
What could change
FDA decisionThe 2026 review is the defining near-term event.REDEFINE 11A longer, modified trial aiming to show greater weight loss than the original.Single-molecule rivalsNovo’s own amycretin and Lilly’s retatrutide could reduce the appeal of two-drug combinations.The amylin classCagriSema is the first amylin-based obesity product to reach filing, leading a fast-moving class.
Legal status
CagriSema is not approved in the US or EU. Novo Nordisk filed a US New Drug Application in December 2025, and an FDA decision is expected during 2026, with possible approval in late 2026 or early 2027. There is no legitimate or gray-market way to obtain the finished combination today; it exists only within trials. If approved, it will be a prescription medicine like Wegovy. Its components, semaglutide and cagrilintide, exist separately, but the studied fixed-dose product does not circulate.
Status current as of July 2026. Regulatory positions change, sometimes quickly.
The market for this
What follows describes how this is bought and sold. It is not a buying guide and it is not an endorsement of any seller.
CagriSema cannot be bought today through any channel, because it is investigational. If approved it will be available by prescription through pharmacies and telehealth, like other branded obesity medicines. It is not, and is unlikely to become, a research-vendor or gray-market product, since it is a regulated fixed-dose combination.
There is no price yet. As a branded next-generation combination from Novo, it would be expected to launch at a premium comparable to or above other branded obesity drugs, with real-world cost shaped by insurance coverage and the same self-pay and rebate dynamics that govern Wegovy.
The only source is Novo Nordisk's regulated manufacturing for trials and, prospectively, commercial supply. There is no gray-market sourcing question for the finished combination, which distinguishes it sharply from the single peptides in this library.
Novo Nordisk (regulated)As an investigational and soon-to-be-filed product, CagriSema is manufactured by Novo under cGMP for trials and, if approved, for commercial supply, a fully controlled chain.Not a gray-market productBecause it is a fixed-dose pharmaceutical combination, CagriSema is not sold by research-chemical vendors the way single peptides are, though its individual components circulate separately.Future commercial supplyIf approved, supply and pricing will follow the same branded, capacity-and-rebate-driven pattern as Wegovy.
What this entry does not yet cover
What follows is unfinished work on our side, not a finding about CagriSema.
Nothing outstanding on this one.
Sources
REDEFINE 1 gave 22.7% mean weight reduction (efficacy estimand) at 68 weeks, published in NEJM
CagriSema achieved 22.7% weight loss but missed the internal 25% weight-loss ambition, prompting a stock decline
Novo Nordisk shares fell after CagriSema data missed the 25% target despite meeting the primary endpoint
Novo Nordisk filed the CagriSema NDA with the FDA on 18 December 2025; review expected in 2026; combination is investigational and not approved
CagriSema is not FDA approved; NDA submitted December 2025 based on REDEFINE 1 and REDEFINE 2, FDA review expected 2026
REDEFINE 2 in adults with type 2 diabetes gave 13.7% to 15.7% mean weight loss vs 3.4% placebo, published in NEJM 2025
Cagrilintide (AM833 / NNC0174-0833) is a long-acting once-weekly amylin analogue built on a pramlintide-like backbone using Novo Nordisk fatty-acid acylation technology
Cagrilintide combined with semaglutide produced additive weight loss in phase 1b, the rationale for the CagriSema fixed combination
REDEFINE 1 filing details: 20.4% weight loss vs 3.0% placebo, 91.9% reached at least 5% loss; indication is obesity/overweight with a weight-related comorbidity
Any CagriSema circulating in the US before approval is unauthorized; broader gray-market and counterfeit GLP-1 risk documented by FDA
The studies that matter
REDEFINE 12024-2025
In 3,417 adults with obesity, CagriSema produced 22.7% weight loss with full adherence, versus 14.9% for semaglutide and 11.5% for cagrilintide alone.
REDEFINE 22025
Confirmed benefit in adults with type 2 diabetes.
REIMAGINE 22026
Beat semaglutide on both weight and blood sugar across all doses tested in type 2 diabetes.