Side-by-side · Research reference
CagrilintidevsDermorphin
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
APhase 3HUMAN-REVIEWED35/64 cited
BAnimal-StrongHUMAN-REVIEWED20/47 cited
Dermorphin
Opioid Peptide · μ-Receptor Agonist · Research Only
Research only · ICV / SC (animal models)
01Mechanism of Action
Parameter
Cagrilintide
Dermorphin
Primary target
Amylin receptor (AMYR) and calcitonin receptor (CTR) heterodimeric complexesBailey 2026
μ-opioid receptors (central and peripheral)Negri 1992Steel 2014
Pathway
AMYR/CTR agonism → Central satiety signaling → Reduced food intake, delayed gastric emptying, suppressed glucagonBailey 2026
μ-receptor activation → G-protein coupling → adenylyl cyclase inhibition → neuronal hyperpolarization
Downstream effect
Central satiety induction, prandial glucagon suppression, reduced caloric intake, weight loss, improved glycemic controlBailey 2026Yamauchi 2026
Potent analgesia, reduced nociceptive signaling, opioid-mediated CNS and peripheral effects
Feedback intact?
Yes — acts via physiological amylin pathways
N/A — exogenous opioid agonist
Origin
Second-generation non-aggregating long-acting amylin analogue designed for once-weekly dosingBailey 2026
Phyllomedusa sauvagei and P. bicolor frog skin — gene-encoded with natural D-amino acid incorporationAmiche 1998Mignogna 1992
02Dosage Protocols
Parameter
Cagrilintide
Dermorphin
Standard dose (combination)
Cagrilintide 2.4 mg + Semaglutide 2.4 mg (CagriSema)Yamauchi 2026
Phase 3 REDEFINE 5 trial dosing.
—
Monotherapy dosing
Dose-dependent, under investigation
Monotherapy trials reported in meta-analysis.
—
Evidence basis
Phase 3 RCT (REDEFINE 5), meta-analysis of 3 RCTs (n=3545)Yamauchi 2026Ahmed 2026
Animal studies · In vitro assays
Legal status
—
Controlled substance in many jurisdictions · Research only
Not approved for human use.
Animal research (ICV)
—
Low nanomolar to picomolar range
Intracerebroventricular administration in rodent models.
Detection limit (doping)
—
5 pg/mL in equine plasma/urineSteel 2014
High-throughput LC-MS/MS screen developed for racing industry.
Duration of action
—
10–120 minutes (dose-dependent, intrathecal)
Human toxicity
—
Kambô ritual (P. bicolor skin) — violent emesis, vasodilation, fluid shifts, ADH dysregulationTran 2025
03Metabolic / Fat Loss Evidence
Parameter
Cagrilintide
Dermorphin
Weight loss vs semaglutide
7.47% greater percentage weight lossAhmed 2026
CagriSema combination vs semaglutide monotherapy (meta-analysis).
—
Absolute weight change
Significantly greater absolute weight reductionAhmed 2026
Mean difference favoring combination therapy.
—
Glycemic benefit
Reduced fasting glucose and HbA1cAhmed 2026
Synergistic effect with semaglutide in combination.
—
Body composition
Predominant fat loss with weight reduction
—
Mitochondrial function
In vitro effects on skeletal muscle mitochondria under metabolic stress conditionsOld 2026
C2C12 myotube study; clinical relevance under investigation.
—
Key publications
REDEFINE 5 (Yamauchi 2026) · Ahmed meta-analysis 2026 · Bailey review 2026Yamauchi 2026Ahmed 2026Bailey 2026
—
04Side Effects & Safety
Parameter
Cagrilintide
Dermorphin
Gastrointestinal
Nausea, diarrhea (common with incretin-based therapies)Pardali 2026
Dietary management and nutritional monitoring recommended.
—
Injection site reactions
Local reactions possible with subcutaneous administration
—
Safety profile
Generally consistent with incretin-based therapies
Phase 3 and meta-analysis safety data.
—
Tolerability
Tolerability considerations similar to GLP-1RAs
—
Muscle preservation
Lean mass considerations during weight loss
In vitro mitochondrial effects observed; clinical impact under investigation.
—
Opioid effects
—
Respiratory depression, sedation, euphoria, tolerance, dependence risk
Kambô ritual toxicity
—
Violent emesis, vasodilation, profound fluid shifts, hyponatremia, ADH dysregulation, brain death (case report)Tran 2025
Receptor selectivity caveat
—
Two μ-receptor subtypes — differential behavioral effects (analgesia vs. catalepsy)Negri 1992
Proteolytic stability
—
Tyr³-Pro⁶ bond relatively unstable; endogenous enzymes may produce tetrapeptide fragmentsCucumel 1996
Absolute Contraindications
Cagrilintide
- ·Hypersensitivity to cagrilintide or formulation components
Dermorphin
- ·Human use — not approved by any regulatory authority
- ·Controlled substance status — possession illegal in many jurisdictions
- ·Known opioid hypersensitivity or respiratory compromise
Relative Contraindications
Cagrilintide
- ·Severe gastrointestinal disease
- ·History of pancreatitis (incretin-based therapy consideration)
Dermorphin
- ·Any context outside approved animal research protocols
- ·CNS depressant co-administration
05Administration Protocol
Parameter
Cagrilintide
Dermorphin
1. Dosing frequency
Once-weekly subcutaneous injection. Long-acting formulation designed for weekly administration schedule.Bailey 2026
Dermorphin is a controlled substance in many jurisdictions and is not approved for human use. Possession, synthesis, or distribution may be illegal. Use is restricted to licensed research settings under institutional review.
2. Combination form
Co-formulated with semaglutide as CagriSema for single weekly injection combining amylin and GLP-1 receptor agonism.Yamauchi 2026Bailey 2026
In rodent models, intracerebroventricular (ICV) or intrathecal injection is used at nanomolar to picomolar concentrations. Subcutaneous administration also documented. All protocols require IACUC approval.
3. Injection site
Subcutaneous — typically abdomen, thigh, or upper arm. Rotate injection sites weekly to minimize local reactions.
High-throughput LC-MS/MS screens developed for anti-doping programs detect dermorphin and 17 related peptides in equine and human urine/plasma at limits as low as 5 pg/mL.Steel 2014
4. Storage
Refrigerate 2–8°C. Follow product-specific storage instructions for pre-filled pens or vials. Protect from light.
Application of Phyllomedusa bicolor skin secretions to superficial burns. Not recommended — associated with severe toxicity including violent emesis, hyponatremia, and documented case of brain death.Tran 2025
5. Dietary considerations
Nutritional monitoring recommended during treatment. Dietary management strategies important for tolerability and outcomes.Pardali 2026
—
06Stack Synergy
Cagrilintide
+ Semaglutide
StrongCagrilintide (amylin receptor agonist) and semaglutide (GLP-1 receptor agonist) act on distinct receptor systems to produce synergistic weight loss through complementary mechanisms — central satiety via amylin pathways plus incretin-mediated glucose control and appetite suppression via GLP-1. Co-formulated as CagriSema, this combination demonstrates 7.5% greater weight loss versus semaglutide monotherapy in Phase 3 trials with additional benefits on glycemic control and lipid parameters.
- CagriSema
- Cagrilintide 2.4 mg + Semaglutide 2.4 mg
- Frequency
- Once weekly subcutaneous
- Duration
- 26–52 weeks (trial data)
- Primary benefit
- Enhanced weight loss, improved glycemic control, multi-pathway metabolic modulation
Dermorphin
— no documented stacks