CagriSema is Novo Nordisk’s investigational combination of cagrilintide, an amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist, delivered from one dual-chamber pen. In its largest trial it produced 22.7 percent weight loss on the estimand that assumes full adherence, more than either component alone, but that fell short of the company’s own pre-trial guidance and, in a separate head-to-head trial, lost on non-inferiority against tirzepatide 15 mg. It is not approved anywhere; an NDA has been filed with the FDA with no public decision date, and no vial sold under this name today is a regulated pharmaceutical product.
Research snapshot
| Peptide category | Investigational fixed-dose combination (cagrilintide + semaglutide) |
| Primary research interest | Weight management; glycemic control in type 2 diabetes |
| Highest available evidence | Large Phase 3 human trials (REDEFINE 1, REDEFINE 2, REDEFINE 4, REIMAGINE 2, REIMAGINE 3) |
| Human research available | Yes, extensive — REDEFINE and REIMAGINE programs, more than 7,000 participants combined |
| Development status | New Drug Application filed with the FDA on December 18, 2025; under review, no public decision date |
| Regulatory status | Not approved anywhere as of this review |
| Last reviewed | September 2026 |
Technical identity (composition)
| Primary name | CagriSema (Novo Nordisk’s investigational name) |
| Composition | Cagrilintide (amylin/calcitonin receptor agonist) + semaglutide (GLP-1 receptor agonist) |
| Share of vial by mass | Stated as equal nominal parts (e.g. “1.0/1.0”, “2.4/2.4”) in every trial and every vendor listing checked |
| Peptide sequence | Not applicable — a two-component mixture; see individual Cagrilintide and Semaglutide pages for each molecule’s sequence |
| Molecular formula | Not applicable — a multi-component mixture, not a single molecular entity |
| CAS Registry Number | Not applicable — no CAS number is assigned to the combination itself |
| Chemical modifications | Not applicable at the combination level; each component carries its own fatty-acid/albumin-binding modifications (see individual pages) |
| Developer or originator | Novo Nordisk |
| Development status | Phase 3 complete for lead indications; NDA under FDA review since December 2025 |
What it is
CagriSema is Novo Nordisk’s fixed-dose combination of cagrilintide, an amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist, delivered from one dual-chamber pen. It is not a repackaging of two approved drugs: neither half is approved on its own for anything, and the combination itself is not approved anywhere. An NDA was filed with the FDA on 18 December 2025 on the strength of the REDEFINE 1 and REDEFINE 2 trials, and the agency has said only that it expects to review the application in 2026. No decision date has been made public, and nothing sold under this name today is a regulated drug product.
What is actually in the vial
Vendor listings examined for this page settle on two totals, 5 mg plus 5 mg and 10 mg plus 10 mg, sold as a single lyophilised blend. Neither total matches a dose Novo Nordisk has ever studied. Every CagriSema trial, from the first phase 1b combination study through the REDEFINE and REIMAGINE phase 3 programmes, has used 1.0/1.0 mg, 1.7/1.7 mg or 2.4/2.4 mg per component; nothing above 2.4 mg per component has been given to a human being in a registered CagriSema trial. A vial sold as 5 mg or 10 mg per component is not a scaled-up version of the trial product. It is a different total entirely, with no dose-finding data behind it at any size.
One listing states its ratio outright and adds a caveat that reads like a disclaimer for a reason: it notes that the exact ratio depends on the vendor’s own formulation. A second sells the identical 5 mg plus 5 mg pairing under one component’s own house code name in place of semaglutide on the certificate, which means a buyer comparing two vials by their stated contents cannot always tell they are looking at the same molecule twice.
None of the listings checked for this page discloses independent third-party purity or identity testing alongside the certificate of analysis. That is the same gap documented across this encyclopedia’s other blend entries, and it matters more here than most: cagrilintide alone has no approval anywhere and no FDA compounding exemption applies to it, so a vial sold as containing cagrilintide is, by that definition, outside the framework that would let anyone verify what is actually inside it.
Potential benefits and research applications
Weight loss, greater than either component given alone
What is being investigated: whether combining an amylin/calcitonin receptor agonist with a GLP-1 receptor agonist produces more weight loss than either drug alone, by acting through two separate hindbrain pathways. How the effect might occur: rat work has shown the two drugs depend on different downstream neurons, the closest evidence the two mechanisms are genuinely additive rather than duplicative. Evidence: REDEFINE 1 reported 22.7 percent weight loss with CagriSema against 16.1 percent for semaglutide alone and 11.8 percent for cagrilintide alone, on the estimand that assumes full adherence. Strength: has been shown in a large, randomised, placebo-controlled human trial. Limitation: the combination fell short of the company’s own pre-trial guidance of roughly 25 percent, and in the one head-to-head trial against tirzepatide whose result has been announced, CagriSema lost on non-inferiority.
Glycemic control in type 2 diabetes
What is being investigated: whether the combination improves HbA1c more than semaglutide or cagrilintide alone in people with type 2 diabetes. How the effect might occur: the same dual-pathway mechanism proposed for weight loss, applied to glucose control. Evidence: REIMAGINE 2 found a statistically significant but modest HbA1c difference of 0.16 percentage points versus semaglutide alone. Strength: has been shown in a large registered human trial. Limitation: the authors themselves describe it as an added benefit rather than a large effect, a much smaller margin than the weight-loss advantage seen in the obesity trials.
Tolerability relative to cagrilintide’s aversive effects, an argument the data complicates
What is being investigated: whether pairing cagrilintide with semaglutide is tolerable enough for long-term use. How the effect might occur: no clear tolerability benefit is proposed; this is the counter-finding rather than a claimed benefit. Evidence: gastrointestinal adverse events affected 79.6 percent of CagriSema recipients against 39.9 percent on placebo, and cagrilintide alone tolerated noticeably better than the combination in the same trial. Strength: has been reported in a large controlled human trial. Limitation: a 2026 network meta-analysis found CagriSema among the agents with the highest discontinuation for adverse events in the entire obesity drug class, which argues against, not for, an added tolerability benefit from combining the two drugs.
What has actually been tested
Unlike most blends on this site, CagriSema has a real clinical trial programme behind it, run entirely by Novo Nordisk. The REDEFINE trials cover obesity and overweight; REDEFINE 1 randomised 3,417 adults with no diabetes to CagriSema 2.4/2.4 mg, semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone or placebo for 68 weeks, and it is the source of nearly every headline figure attached to this name. The REIMAGINE trials cover type 2 diabetes. Both programmes finished their pivotal readouts in 2025 and 2026, and the picture that emerges is more complicated than the marketing suggests.
On the trial-product estimand, which assumes full adherence to the assigned dose, REDEFINE 1 reported 22.7 percent weight loss with CagriSema against 16.1 percent for semaglutide alone, 11.8 percent for cagrilintide alone and 2.3 percent for placebo. On the treatment-policy estimand, the figure regulators treat as primary because it counts everyone regardless of adherence, CagriSema came in at 20.4 percent. Both numbers are published; they answer different questions, and a page or vendor quoting one without saying which is not necessarily wrong, just incomplete.
The combination beat each of its own components by a wide margin, which is the entire pharmacological argument for combining them. Semaglutide acts on the GLP-1 receptor; cagrilintide acts on amylin and calcitonin receptors in a different part of the hindbrain. Rat work has shown the two drugs depend on different downstream neurons: knocking down a population of prolactin-releasing-hormone neurons in the nucleus of the solitary tract abolished cagrilintide’s effect in that study but left semaglutide’s intact. That is the closest thing to direct evidence that the two mechanisms are genuinely separate rather than two names for the same effect. The honest word for how they combine is additive, not synergistic: added together, the two components’ individual effects over placebo summed to slightly more than what the combination actually delivered.
Amounts studied in human trials
Figures below summarize the cagrilintide/semaglutide doses used in Novo Nordisk’s registered clinical trials. This site does not reproduce a vendor or community dosing schedule for CagriSema; see “What circulates, and why no numbers appear here” further down this page for why.
| Trial | Population | Dose studied | Frequency | Duration | Evidence category |
| Phase 1b (NCT03600480) | n=95, co-escalation study | Cagrilintide 0.16–4.5 mg + semaglutide 2.4 mg | Weekly, co-escalated | 20 weeks | Published human clinical trial |
| REDEFINE 1 | n=3,417, obesity without diabetes | 2.4 mg / 2.4 mg | Weekly, flexible titration | 68 weeks | Published human clinical trial |
| REDEFINE 2 | n=1,206, obesity with type 2 diabetes | 2.4 mg / 2.4 mg | Weekly, flexible titration | 68 weeks | Published human clinical trial |
| REDEFINE 4 | n=809, head-to-head vs. tirzepatide 15 mg | 2.4 mg / 2.4 mg | Weekly, flexible titration | 84 weeks | Published human clinical trial |
| REIMAGINE 2 | n=2,713, type 2 diabetes | 2.4 mg / 2.4 mg | Weekly, flexible titration | Not specified in source | Published human clinical trial |
| REIMAGINE 3 | n=274, basal-insulin add-on | 2.4 mg / 2.4 mg | Weekly, flexible titration | Not specified in source | Published human clinical trial |
Every registered CagriSema trial has used the same 2.4 mg/2.4 mg maintenance target (after a Phase 1b range-finding study), reached through a multi-step titration schedule. Vendor-sold vials are commonly labeled “5 mg + 5 mg” or “10 mg + 10 mg” per vial — quantities that describe the total peptide content of the vial, not a per-injection dose, and that do not correspond to any dose Novo Nordisk has studied. No community- or vendor-reported dosing schedule is reproduced on this page; see the section below for why.
The gap between guidance and the trial
Novo Nordisk had guided investors to expect roughly 25 percent weight loss from CagriSema before REDEFINE 1 reported. The trial met every prespecified endpoint at high statistical significance and still delivered 22.7 percent, and the company’s shares fell by roughly 20 to 26 percent in a single trading session on 20 December 2024. The trial did not fail. The company’s own explanation, stated in its topline announcement, is that the protocol allowed dose flexibility, and only 57.3 percent of CagriSema participants were still on the top dose at week 68, against 82.5 percent for cagrilintide alone and 70.2 percent for semaglutide alone. Guidance built on two small early trials, a 95-person phase 1b and a 92-person phase 2, was always an extrapolation, and a large pragmatic trial with real-world dose adjustment landed a few points under it.
A second result belongs next to that one. In February 2026 Novo Nordisk reported that REDEFINE 4 did not meet its primary endpoint of non-inferiority against tirzepatide 15 mg: 23.0 percent versus 25.5 percent on the efficacy estimand, 20.2 versus 23.6 percent on the treatment-regimen estimand. REDEFINE 4 is the only head-to-head trial against tirzepatide in the obesity, non-diabetic population, and the only one whose result has been announced; two further head-to-head trials against tirzepatide in people with type 2 diabetes have completed but remain unpublished. CagriSema produced a very large effect in REDEFINE 4 and still lost the only head-to-head comparison whose result is public. Any page describing this combination as the most effective obesity treatment available is asserting something that trial did not show.
Tolerability
Gastrointestinal adverse events affected 79.6 percent of CagriSema recipients in REDEFINE 1, against 39.9 percent on placebo, roughly double. A 2026 network meta-analysis found CagriSema among the agents with the highest rate of discontinuation for adverse events in the entire obesity drug class, and a separate meta-analysis found administration-site reactions occurred more than three times as often as with semaglutide alone. Cagrilintide monotherapy in the same trial tolerated noticeably better than the combination, which is the tolerability argument behind Novo Nordisk’s decision to also develop cagrilintide on its own. No severe hypoglycaemia was reported in the basal-insulin add-on trial, the highest-risk setting in the programme, which is a genuine reassurance and belongs alongside the gastrointestinal figures rather than instead of them.
What circulates, and why no numbers appear here
This site does not reproduce a dosing schedule for CagriSema, because the compound is unapproved, and because the escalation schedule is exactly where an unverified vial does the most harm. One widely used protocol page online applies a 16-week titration ladder, 0.25, 0.5, 1.0, 1.7, then 2.4 mg of each component, to CagriSema as though it were an established regimen. That ladder is the escalation used for Wegovy. Cagrilintide’s own phase 2 dose-finding trial escalated over up to six weeks, not sixteen, and the phase 3 CagriSema trials used a flexible, investigator-managed schedule that let more than 40 percent of participants land below the top dose by week 68. A ladder built by pattern-matching one drug’s approved schedule onto an unapproved combination is not the schedule any trial actually used.
The same page states “2.4 mg + 2.4 mg once weekly” as a maintenance dose in the same breath it cites REDEFINE 1 and 2, without noting that neither of those trials, nor any other CagriSema trial, has produced an approved dose for anything. A trial dose and an approved dose are not the same claim, and printing the first as though it were the second is the pattern this section exists to correct.
Regulatory status
CagriSema is not approved anywhere as of this writing. The FDA has the NDA under review with no public decision date. No EU marketing authorisation application has been publicly confirmed. Cagrilintide as a standalone drug has no filing anywhere and will not have phase 3 results before 2027 at the earliest. Nothing sold today under the CagriSema name, in any vial, at any ratio, is a regulated pharmaceutical product, and current FDA policy treats cagrilintide as ineligible for compounding in the United States because it has no approval and no shortage-based exemption applies to it.
Frequently asked questions
What is CagriSema?
CagriSema is Novo Nordisk’s investigational fixed-dose combination of cagrilintide and semaglutide, delivered from one dual-chamber pen. It is not approved anywhere; an NDA is under FDA review with no public decision date.
How does it work?
It pairs an amylin/calcitonin receptor agonist (cagrilintide) with a GLP-1 receptor agonist (semaglutide). Rat work suggests the two act through different neuron populations in the hindbrain, which is the basis for expecting an additive rather than duplicated effect.
What dosage has been studied?
Every registered CagriSema trial has used 1.0/1.0 mg, 1.7/1.7 mg or 2.4/2.4 mg per component, on a flexible, investigator-managed titration schedule. Nothing above 2.4 mg per component has been given to a human being in a registered trial of this combination.
What dosage commonly circulates online?
Vendor listings settle on 5 mg plus 5 mg or 10 mg plus 10 mg per vial, totals that do not match any dose Novo Nordisk has studied. One widely used protocol applies Wegovy’s 16-week titration ladder to CagriSema as though it were an established regimen; no CagriSema trial used that schedule. This site does not reproduce a dosing schedule for this compound, because it is unapproved and the escalation schedule is exactly where an unverified vial does the most harm.
Has it been studied in humans?
Yes, extensively, across the REDEFINE (obesity) and REIMAGINE (type 2 diabetes) trial programmes, which together enrolled well over 7,000 participants. That real clinical trial record does not extend to the ratios or totals sold in vendor vials.
Is it more effective than semaglutide or tirzepatide?
It beat semaglutide and cagrilintide alone by a wide margin in REDEFINE 1. Against tirzepatide, the only announced head-to-head trial, REDEFINE 4, found CagriSema did not meet non-inferiority: 23.0 percent versus 25.5 percent on the efficacy estimand.
Why did the stock drop when the phase 3 results came out?
Novo Nordisk had guided investors to expect roughly 25 percent weight loss. REDEFINE 1 met every prespecified endpoint at high statistical significance and still delivered 22.7 percent, and shares fell 20 to 26 percent in a single session. The company attributes the gap mainly to flexible dosing: only 57.3 percent of CagriSema participants were still on the top dose at week 68.
What side effects have been reported?
Gastrointestinal adverse events affected 79.6 percent of recipients against 39.9 percent on placebo. A 2026 network meta-analysis found CagriSema among the agents with the highest discontinuation for adverse events in the entire obesity drug class, and administration-site reactions occurred more than three times as often as with semaglutide alone.
Is it approved?
No. An NDA was filed with the FDA on 18 December 2025; the agency has said only that it expects to review it in 2026, with no public decision date. No EU filing has been publicly confirmed.
What remains unknown?
Whether and when it will be approved; why its advantage over semaglutide alone was large in the obesity trials but much smaller in the diabetes trial; whether it affects cardiovascular, kidney or bone outcomes, since no amylin receptor agonist has completed a cardiovascular outcomes trial; what happens to weight after stopping; and whether vials sold under this name contain what their labels claim.
Bottom line
CagriSema is a real, extensively studied combination with a genuine pharmacological rationale: two hindbrain pathways that rat evidence suggests work through different neurons rather than one. It produced the largest weight loss of any regimen in its own trial programme, 22.7 percent against placebo’s 2.3 percent, and clearly beat both of its individual components. But it also missed the company’s own pre-trial guidance, lost the only announced head-to-head trial against tirzepatide, and carries a gastrointestinal side-effect burden roughly double placebo’s. It is not approved anywhere, and every dose sold in a vendor vial, at every ratio checked for this page, is well above anything a registered trial has tested in a human being. What is published is real clinical evidence; what circulates in a vial is not the same product the trials tested.