Also known as: NNC0487-0111
Chronic weight management in adults with obesity or overweight
Amount
1.25-60 mg (SC) or up to 100 mg (oral)
Frequency
Once weekly (SC) or once daily (oral)
Duration
Up to 36 weeks (Phase 1b/2a)
Route
SCSchedule
Once weekly (subcutaneous formulation)
Timing
Dose escalation required. SC formulation administered weekly; oral formulation with SNAC enhancer taken daily. Both formulations under investigation.
Duration
Ongoing (long-term use expected)
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 factors
CMP
When: 12 weeks
Why: Monitor metabolic parameters during treatment
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Amycretin (NNC0487-0111) is a first-in-class unimolecular dual GLP-1 and amylin receptor agonist developed by Novo Nordisk. It is a single 68-amino-acid peptide engineered to activate both the glucagon-like peptide-1 (GLP-1) receptor and the amylin receptor, combining two complementary appetite and metabolic regulatory pathways in one molecule.
Amycretin is distinguished from CagriSema (also by Novo Nordisk), which combines separate cagrilintide (amylin agonist) and semaglutide (GLP-1 agonist) peptides in a single injection. By incorporating both activities into a single molecular entity, amycretin potentially offers simpler manufacturing, more predictable pharmacokinetics, and different receptor binding characteristics.
In Phase 1b/2a trials published in The Lancet, subcutaneous amycretin achieved up to 24.3% weight loss at 36 weeks (60 mg dose), positioning it among the most effective anti-obesity therapies in clinical development. An oral formulation achieved up to 13.1% weight loss at 12 weeks.
Amycretin activates both GLP-1 and amylin receptors through a single molecule:
GLP-1 receptor activation:
Amylin receptor activation:
The dual GLP-1/amylin mechanism provides additive effects on appetite suppression and weight loss, as these pathways activate different neuronal populations in the brainstem and hypothalamus. This is the same rationale behind CagriSema, but delivered through a single molecule.
The first-in-human Phase 1 trial (PMID 40550229, Lancet 2025) evaluated oral amycretin with SNAC permeation enhancer in 144 participants. Oral amycretin achieved up to 13.1% weight loss at 12 weeks (2x50 mg dose).
The Phase 1b/2a trial (PMID 40550231, Lancet 2025) enrolled 125 participants with overweight or obesity. Key results:
A Phase 2 trial in 448 people with T2D inadequately controlled on metformin showed:
Novo Nordisk plans to initiate Phase 3 development for both obesity and T2D in 2026.
Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study, published in The Lancet (Dahl K et al., 2025; PMID: 40550231):
Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial, published in The Lancet (Novo Nordisk investigators, 2025; PMID: 40550229):
We summarize new studies, safety updates, and dosing insights โ delivered biweekly.
See real-world usage patterns alongside the clinical evidence above. Community-sourced, not clinically verified.
0View community protocolsCagriSema: cagrilintide + semaglutide combination by Novo Nordisk. REDEFINE 1 showed 20.4% weight loss at 68 weeks. Mechanism, trial data, and NDA status.
GUBamy (GUB014295): dual amylin/calcitonin receptor agonist (DACRA) by Gubra. AbbVie licensed for $350M. Phase 1 showed 7.77% weight loss in 43 days.
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.
Amycretin shows potentially superior weight loss (up to 24.3% in Phase 1b/2a) compared to semaglutide (14.9% in STEP 1), driven by its dual GLP-1/amylin mechanism in a single molecule. The ability to offer both injectable and oral formulations without fasting restrictions is a significant advantage. However, these are early-phase results with small sample sizes and short duration. Semaglutide remains the proven, FDA-approved standard with cardiovascular benefit and extensive safety data. Amycretin is Novo Nordisk's most promising pipeline asset, but Phase 3 confirmation is needed before definitive comparisons can be made.
Amycretin's early-phase data (24.3% weight loss at 36 weeks, no plateau) suggest it could substantially exceed tirzepatide's 20.9%, potentially becoming the most effective anti-obesity agent ever tested. However, this comparison is fundamentally unequal: amycretin's results come from 125 patients over 36 weeks, while tirzepatide's come from thousands of patients over 72 weeks in rigorous Phase 3 trials. Early-phase weight loss often diminishes in larger trials. Tirzepatide is FDA-approved and available today. Amycretin's promise must be confirmed in Phase 3 before definitive conclusions can be drawn.
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.
A comprehensive guide to every oral GLP-1 obesity drug in development, from approved oral semaglutide to pipeline agents orforglipron, aleniglipron, VK2735, ribupatide, and amycretin.
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