Also known as: Cagrilintide/Semaglutide, NNC0174-0833
Chronic weight management in adults with obesity or overweight
Amount
Cagrilintide 2.4 mg + semaglutide 2.4 mg
Frequency
Once weekly
Duration
68 weeks (Phase 3 trials)
Route
SCSchedule
Once weekly
Timing
Single injection from pre-filled pen combining both agents. Gradual dose escalation over 16-20 weeks to reach target maintenance dose. Inject on the same day each week, any time of day, without regard to meals.
Duration
Ongoing (long-term use intended)
Repeatable
Yes
CMP (Comprehensive Metabolic Panel)
When: Baseline
Why: Baseline liver and kidney function
HbA1c
When: Baseline
Why: Baseline glycemic status
Lipid panel
When: Baseline
Why: Baseline cardiovascular risk assessment
HbA1c and lipid panel
When: 16 weeks
Why: Monitor metabolic improvements after reaching maintenance dose
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CagriSema is a once-weekly injectable combination of cagrilintide and semaglutide, developed by Novo Nordisk for the treatment of obesity and type 2 diabetes. The combination pairs two distinct hormonal pathways -- amylin receptor agonism (via cagrilintide) and GLP-1 receptor agonism (via semaglutide) -- in a single subcutaneous injection at doses of 2.4 mg each.
Cagrilintide is a long-acting acylated analog of human amylin, a 37-amino-acid peptide hormone co-secreted with insulin from pancreatic beta-cells. Amylin acts on receptors in the area postrema and nucleus tractus solitarius of the brainstem to reduce food intake, slow gastric emptying, and suppress glucagon secretion. Semaglutide is the well-established GLP-1 receptor agonist that forms the basis of Ozempic and Wegovy.
The rationale for the combination is that amylin and GLP-1 regulate appetite and energy balance through complementary neural pathways, and their combined activation produces greater weight loss than either agent alone. This was confirmed in the REDEFINE Phase 3 program, where CagriSema achieved 20.4% mean weight loss versus 14.9% for semaglutide alone and 11.5% for cagrilintide alone.
CagriSema activates two distinct incretin/hormonal pathways simultaneously:
Semaglutide (GLP-1 receptor agonist):
Cagrilintide (amylin receptor agonist):
The combination produces additive or synergistic effects on appetite suppression and weight loss because amylin and GLP-1 signal through different receptor systems and partially distinct neural circuits.
The REDEFINE 1 trial (NEJM 2025) enrolled 3,417 adults with obesity or overweight with comorbidities but without diabetes. Participants were randomized 21:3:3:7 to CagriSema, semaglutide alone, cagrilintide alone, or placebo for 68 weeks.
Mean weight loss at 68 weeks:
Among CagriSema-treated participants, 60% achieved at least 20% weight loss and 23% achieved at least 30% weight loss. Additionally, 88% of participants with prediabetes returned to normoglycemia.
REDEFINE 2 (NEJM 2025) enrolled 1,206 adults with obesity and type 2 diabetes, randomized to CagriSema or placebo for 68 weeks. CagriSema achieved 13.7% mean weight loss versus 3.4% with placebo. Among those receiving CagriSema, 73.5% achieved HbA1c of 6.5% or lower.
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1), published in New England Journal of Medicine (Aronne LJ et al., 2025; PMID: 40544433):
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2), published in New England Journal of Medicine (Lingvay I et al., 2025; PMID: 40544432):
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View community protocolsAmycretin: Novo Nordisk unimolecular GLP-1/amylin receptor agonist. Phase 1b/2a showed up to 24.3% weight loss at 36 weeks. SC and oral formulations. Phase 3 planned.
Mazdutide: Dual GLP-1/glucagon agonist approved in China for obesity. Covers up to 20% weight loss in trials, mechanism, dosing, and side effects.
Retatrutide: Triple GIP/GLP-1/glucagon agonist with up to 24% weight loss. Covers mechanism, Phase 2/3 trial data, dosing, and side effects.
Semaglutide: FDA-approved GLP-1 agonist for weight loss and diabetes. Covers STEP/SUSTAIN trials, Ozempic vs Wegovy dosing, and cardiovascular benefits.
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.
Both amycretin and CagriSema are Novo Nordisk programs targeting the same GLP-1 plus amylin dual pathway, but with fundamentally different molecular strategies. CagriSema has the stronger evidence base with completed phase 3 REDEFINE trials showing 20.4% weight loss, and is closer to potential approval. Amycretin offers the elegance of a single molecule activating both pathways, with the critical advantage of an oral formulation and phase 1b/2a data showing up to 24% weight loss at 36 weeks. If amycretin's early data holds in phase 3, its oral availability could make it the preferred option. CagriSema's advantage is the ability to independently optimize the dose of each component.
CagriSema and retatrutide represent two fundamentally different approaches to next-generation obesity treatment. CagriSema combines two proven mechanisms (amylin + GLP-1) in a fixed-dose injection, achieving 20.4% weight loss in Phase 3, with an NDA already filed and the advantage of building on the well-characterized semaglutide platform. Retatrutide's novel triple-agonist approach produced 28.7% weight loss in Phase 3 TRIUMPH-4 (confirming 24.2% in Phase 2) by adding glucagon and GIP receptor activation. CagriSema is likely to reach market sooner, but retatrutide offers the greatest peak efficacy of any single anti-obesity agent.
CagriSema demonstrates meaningfully greater weight loss than semaglutide alone (20.4% vs 14.9%), driven by the complementary amylin pathway from cagrilintide. REDEFINE 1 showed CagriSema was superior to semaglutide alone, cagrilintide alone, and placebo. However, semaglutide has proven cardiovascular benefit (SELECT), 7+ years of safety data, oral formulation options, and established availability. CagriSema represents the next step for patients who need greater weight loss than semaglutide alone can provide, once it becomes available.
CagriSema and tirzepatide achieve remarkably similar weight loss (20.4% vs 20.9%) through fundamentally different dual mechanisms -- amylin/GLP-1 versus GIP/GLP-1. This positions them as the two leading next-generation obesity treatments. Tirzepatide has the advantage of FDA approval and growing real-world experience. CagriSema is filed for approval and represents Novo Nordisk's competitive response. Without a head-to-head trial, definitive superiority cannot be established. The choice may ultimately depend on individual response, tolerability, and prescriber experience.
A comprehensive guide to every GLP-1 receptor agonist drug, from FDA-approved semaglutide and tirzepatide to pipeline therapies like retatrutide, amycretin, MariTide, and oral orforglipron.
A research review of GLP-1 and amylin combination therapy for obesity, covering CagriSema, amycretin, petrelintide, pramlintide, and the science behind dual appetite hormone targeting.
Every GLP-1 and incretin drug ranked by clinical weight loss data as of 2026, from retatrutide at 28.7% to oral orforglipron at 11.2%, with comparison tables and trial details.
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