CagriSema
The first fixed-dose GLP-1 plus amylin combination, pairing semaglutide and cagrilintide in a single once-weekly injection for deep weight loss.
CagriSema is Novo Nordisk's investigational fixed-dose combination of semaglutide (the GLP-1 agonist in Ozempic and Wegovy) and cagrilintide (a long-acting amylin analog), both at 2.4 mg in a dual-chamber pen given once weekly. It attacks two appetite pathways at once, producing 22.7% mean weight loss over 68 weeks in the phase 3 REDEFINE-1 trial, the second-deepest phase 3 obesity result ever recorded. Novo filed the NDA in December 2025 with an FDA decision expected in late 2026; in a head-to-head trial (REDEFINE-4) it came in behind tirzepatide 15 mg and missed its non-inferiority endpoint.
Class
Fixed-dose GLP-1 receptor agonist + amylin analog combination
Half-life
~168 hours (approximately 7 days) for both components, supporting once-weekly dosing
Routes
Subcutaneous injection (dual-chamber pen)
Category
Weight Loss & Metabolic
Researched benefits
What it's studied for
Deep weight loss
REDEFINE-1 delivered 22.7% mean weight loss over 68 weeks in 3,417 patients, the second-deepest phase 3 obesity result ever recorded (behind retatrutide). For an average 240-pound starting patient that is roughly 54 pounds lost from a weekly shot.
Superior to either agent alone
In REDEFINE-1 the combination reached 22.7% versus 16.1% for semaglutide monotherapy and 11.8% for cagrilintide monotherapy, confirming a genuine additive combination effect rather than rebranded GLP-1.
High responder rates
60% of CagriSema patients hit at least 20% body-weight loss and 40.4% reached at least 25%, an unusually large share of deep responders for an injectable obesity therapy.
Glycemic control in type 2 diabetes
In REDEFINE-2 (n=1,206, T2D patients), 73.5% of CagriSema patients achieved HbA1c at or below 6.5% versus 15.9% on placebo, alongside 13.7% weight loss, both clinically meaningful endpoints.
Dual complementary mechanism
By combining GLP-1 satiety and delayed gastric emptying with amylin-driven meal-associated satiety and glucagon suppression, CagriSema engages two distinct appetite pathways in a single weekly injection.
Mechanism
How it works
CagriSema combines two peptides that regulate appetite through separate but complementary receptor systems. Semaglutide, the GLP-1 receptor agonist, slows gastric emptying and suppresses post-meal hunger by acting on the hindbrain, the same mechanism behind Ozempic and Wegovy.
Cagrilintide is a long-acting amylin analog that binds amylin and calcitonin receptors in the area postrema, reinforcing meal-related satiety and suppressing glucagon. Because amylin signaling is a distinct pathway from GLP-1, adding it layers a second brake on food intake on top of the GLP-1 effect.
The result is additive appetite suppression. In REDEFINE-1 the combination produced 22.7% weight loss versus 16.1% for semaglutide alone and 11.8% for cagrilintide alone, demonstrating that the two mechanisms stack. The same additivity that deepens weight loss also raises the gastrointestinal side-effect burden relative to semaglutide monotherapy.
Both components have a half-life of roughly 168 hours, allowing them to be co-formulated at 2.4 mg each in a dual-chamber pen for once-weekly subcutaneous dosing.
Dosing protocols
Dosing & administration
Dosing reflects protocols reported in research and community literature for educational purposes. It is not medical advice or a recommendation. Most peptides here are not approved for human use.
Clinical (trial titration)
- Dose
- Low starting dose escalated toward 2.4 mg / 2.4 mg
- Frequency
- Once weekly
- Timing
- Same day each week
- Duration
- Titration over several months, then maintenance
- Route
- Subcutaneous injection
Trial titration follows a schedule similar to Wegovy, starting low and escalating over several months to limit gastrointestinal side effects.
Target maintenance
- Dose
- Semaglutide 2.4 mg + cagrilintide 2.4 mg (fixed-dose)
- Frequency
- Once weekly
- Timing
- Same day each week
- Duration
- Chronic (ongoing)
- Route
- Subcutaneous injection (dual-chamber pen)
The full maintenance dose used in the REDEFINE phase 3 program. Final approved dosing will be set by regulatory review.
- CagriSema is not commercially available; the dosing above reflects the REDEFINE clinical trial regimen, not an approved label.
- Titration is used to manage gastrointestinal tolerability, mirroring the escalation approach used for Wegovy.
- As with the rest of the GLP-1 class, this is a chronic-medication model and weight rebound is expected on discontinuation.
- Dose and protocol decisions belong with a clinician; investigational access is limited to clinical trials before approval.
Evidence
Research & clinical studies (3)
REDEFINE-1: CagriSema in adults with obesity
In 3,417 patients with obesity, CagriSema produced 22.7% mean weight loss at 68 weeks (trial product estimand; 20.4% treatment policy estimand), significantly superior to placebo, semaglutide alone (16.1%), and cagrilintide alone (11.8%).
REDEFINE-2: CagriSema in adults with type 2 diabetes
In 1,206 patients with type 2 diabetes, 73.5% of CagriSema patients achieved HbA1c at or below 6.5% versus 15.9% on placebo, with 13.7% weight loss.
REDEFINE-4: CagriSema versus tirzepatide 15 mg head-to-head
In 809 patients over 84 weeks, CagriSema achieved 23.0% weight loss versus 25.5% for tirzepatide 15 mg, missing its non-inferiority primary endpoint in February 2026.
Combinations
Stacking & blends
CagriSema (co-formulated combination)
Maximize weight loss by engaging two appetite pathways at once
CagriSema is itself a fixed-dose combination: semaglutide provides GLP-1 satiety and delayed gastric emptying while cagrilintide adds amylin-driven satiety, producing additive weight loss beyond either agent alone.
Safety
Side effects & considerations
Commonly reported effects
Contraindications & cautions
- Not available for lawful US pharmacy use outside clinical trials before approval
- Standard GLP-1 class cautions apply pending final label
Gastrointestinal adverse events reached 79.6% on CagriSema versus 39.9% on placebo in REDEFINE-1, higher than semaglutide monotherapy because the amylin component adds GI burden. Despite this, discontinuation rates stayed low (5.9% CagriSema vs 3.5% placebo). Weight rebound is expected on discontinuation, consistent with the chronic-medication model of the GLP-1 class. The full safety profile is pending completion of regulatory review.
FAQ
CagriSema — common questions
What is CagriSema?
CagriSema is an investigational combination drug from Novo Nordisk containing two peptides: cagrilintide (a long-acting amylin analog) and semaglutide (the GLP-1 agonist behind Ozempic and Wegovy). It pairs two complementary appetite-regulation mechanisms in a single weekly injection.
What does CagriSema do?
It targets two appetite pathways simultaneously: GLP-1 (satiety and delayed gastric emptying) and amylin (meal-associated satiety and glucagon suppression). Phase 3 REDEFINE data show weight loss greater than semaglutide or cagrilintide alone, though REDEFINE-4 showed tirzepatide remained stronger head-to-head.
How is CagriSema administered?
It is a once-weekly subcutaneous injection in clinical trials, using a dual-chamber pen holding semaglutide and cagrilintide at 2.4 mg each. Dosing titration follows a schedule similar to Wegovy, starting low and escalating over several months. Final approved dosing will be determined by regulatory review.
Does CagriSema work better than tirzepatide?
No, on the head-to-head data. REDEFINE-4 directly compared CagriSema against tirzepatide 15 mg and CagriSema lost, 23.0% versus 25.5% weight loss, missing its non-inferiority endpoint. CagriSema works very well and is the number-two drug in its class, but tirzepatide keeps the crown.
What are the side effects of CagriSema?
Side effects are primarily gastrointestinal, nausea, vomiting, diarrhea, and constipation, consistent with the GLP-1 class. The amylin component adds additional GI burden, with GI adverse events reaching 79.6% in REDEFINE-1, higher than semaglutide monotherapy, though discontinuation rates stayed low.
Is CagriSema FDA approved?
No. Novo Nordisk filed the NDA on December 18, 2025 and CagriSema remains investigational under FDA review, with a decision expected in late 2026. It is not on an FDA bulk pathway for compounding, so lawful US pharmacy access does not exist outside clinical trials before approval.
How much does CagriSema cost?
It is not yet commercially available, so no retail price exists. If approved, pricing is expected to align with branded weight-loss GLP-1 drugs at roughly $1,000-1,500 per month without insurance. Any vendor versions are gray-market research supply, not equivalent to Novo's dual-chamber clinical product.
