Side-by-side · Research reference
CagrilintidevsSS-31
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
BPhase 3HUMAN-REVIEWED9/43 cited
SS-31
Cardiolipin-binding · Mitochondrial protective
SQ · Abdomen · Once daily
01Mechanism of Action
Parameter
Cagrilintide
SS-31
Primary target
Amylin receptor (AMYR) and calcitonin receptor (CTR) heterodimeric complexesBailey 2026
Cardiolipin in inner mitochondrial membraneSzeto 2014
Pathway
AMYR/CTR agonism → Central satiety signaling → Reduced food intake, delayed gastric emptying, suppressed glucagonBailey 2026
Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014Szilagyi 2009
Downstream effect
Central satiety induction, prandial glucagon suppression, reduced caloric intake, weight loss, improved glycemic controlBailey 2026Yamauchi 2026
Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014
Feedback intact?
Yes — acts via physiological amylin pathways
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Origin
Second-generation non-aggregating long-acting amylin analogue designed for once-weekly dosingBailey 2026
Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014
Antibody development
—
—
02Dosage Protocols
Parameter
Cagrilintide
SS-31
Standard dose (combination)
Cagrilintide 2.4 mg + Semaglutide 2.4 mg (CagriSema)Yamauchi 2026
Phase 3 REDEFINE 5 trial dosing.
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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
Multiple Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014Szilagyi 2009
Duration
26–52 weeks in trialsYamauchi 2026
Indefinite for mitochondrial disease; cycled for healthspan use
Standard dose
—
40 mg / day SQ (clinical trials)Szeto 2014
Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.
Lower / starter dose
—
5 mg / day (anecdotal)
Reconstitution
—
Bacteriostatic water
Timing
—
Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress
Half-life
—
~3 h plasma; tissue uptake longer
03Metabolic / Fat Loss Evidence
Parameter
Cagrilintide
SS-31
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.
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Body composition
Predominant fat loss with weight reduction
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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
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04Side Effects & Safety
Parameter
Cagrilintide
SS-31
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
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Muscle preservation
Lean mass considerations during weight loss
In vitro mitochondrial effects observed; clinical impact under investigation.
—
Injection site reaction
—
Erythema, mild pruritus
GI symptoms
—
Nausea (uncommon)
Headache
—
Reported in some Phase 3 trials
Cardiovascular
—
Cardio-protective in studies; no signal of harm
Pregnancy / OB
—
Avoid — insufficient data
Absolute Contraindications
Cagrilintide
- ·Hypersensitivity to cagrilintide or formulation components
SS-31
- ·Pregnancy / breastfeeding
- ·Hypersensitivity to peptide
Relative Contraindications
Cagrilintide
- ·Severe gastrointestinal disease
- ·History of pancreatitis (incretin-based therapy consideration)
SS-31
- ·None established
05Administration Protocol
Parameter
Cagrilintide
SS-31
1. Dosing frequency
Once-weekly subcutaneous injection. Long-acting formulation designed for weekly administration schedule.Bailey 2026
Add bacteriostatic water per label. Light-protected handling.
2. Combination form
Co-formulated with semaglutide as CagriSema for single weekly injection combining amylin and GLP-1 receptor agonism.Yamauchi 2026Bailey 2026
SQ — abdomen or thigh. Rotate sites.
3. Injection site
Subcutaneous — typically abdomen, thigh, or upper arm. Rotate injection sites weekly to minimize local reactions.
Morning fasted; pre-workout for exercise-augmented mitochondrial stress.
4. Storage
Refrigerate 2–8°C. Follow product-specific storage instructions for pre-filled pens or vials. Protect from light.
Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.
5. Dietary considerations
Nutritional monitoring recommended during treatment. Dietary management strategies important for tolerability and outcomes.Pardali 2026
29–31G, 4–8 mm insulin syringe.
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
SS-31
+ MOTS-c
ModerateSS-31 and MOTS-c address mitochondrial decline through complementary axes. SS-31 protects existing mitochondrial structure (cardiolipin binding, cristae stabilisation). MOTS-c upregulates AMPK/PGC-1α, triggering biogenesis of new mitochondria. Together they pair preservation with renewal — anecdotally favoured in healthspan and post-cardio-event recovery protocols.
- SS-31
- 5–10 mg SQ · daily morning
- MOTS-c
- 5 mg SQ · 2× per week pre-workout
- Primary benefit
- Mitochondrial preservation + biogenesis