Side-by-side · Research reference

DihexavsRetatrutide

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED7/28 cited

BPhase 2HUMAN-REVIEWED10/41 cited

Dihexa

Angiotensin IV Analogue · Pre-Clinical

Pre-clinicalDevelopment stage

Rodent onlyEvidence basisBenoist 2014

HGF/c-MetTarget systemWright 2015

Not established — animal studies only

Retatrutide

Triple-receptor agonist · Phase 3

1–12 mgWeekly doseJastreboff 2023

24.2%Body-weight ↓Jastreboff 2023

~6 daysHalf-life (est)

SQ · Abdomen · Once weekly

01Mechanism of Action

Parameter

Dihexa

Retatrutide

Primary target

c-Met receptor (HGF receptor tyrosine kinase)

GLP-1R + GIPR + Glucagon receptor (triple agonism)Jastreboff 2023

Pathway

HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization

Triple-receptor activation → ↑insulin (GLP-1+GIP), ↓gastric emptying, ↑lipid handling, ↑energy expenditure (glucagon component)Jastreboff 2023

Downstream effect

Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models

Maximal weight loss across class. Glucagon component drives lipolysis and energy expenditure beyond GLP-1+GIP aloneJastreboff 2023

Feedback intact?

—

Origin

Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015

Synthetic peptide engineered for balanced affinity at three incretin / glucagon receptorsJastreboff 2023

Antibody development

—

02Dosage Protocols

Parameter

Dihexa

Retatrutide

Human dosing

Not established — no human trials

—

Animal studies

Mouse/rat models only — dosing not translatable to humans

—

Evidence basis

Pre-clinical / Rodent models

Phase 2 trial; Phase 3 ongoingJastreboff 2023

Clinical status

No Phase 1, 2, or 3 trials published

—

Standard dose

—

12 mg / week (max efficacy)Jastreboff 2023

Phase 2 trial dose. Phase 3 dosing TBD.

Frequency

—

Once weekly

Titration schedule

—

2 mg → 4 mg → 8 mg → 12 mg over 16 weeks

Duration

—

Indefinite for chronic indication (presumed)

Reconstitution

—

Investigational; not commercially available

Timing

—

Any time of day

Half-life

—

~6 days (estimated from class)

04Side Effects & Safety

Parameter

Dihexa

Retatrutide

Human safety data

None available — no human clinical trials

—

Theoretical c-Met risks

c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile

—

Pre-clinical tolerability

Not systematically reported in available studies

—

GI symptoms

—

Nausea, vomiting, diarrhea (very common, dose-dependent)Jastreboff 2023

Heart rate

—

↑ resting HR (3–7 bpm at 12 mg)Jastreboff 2023

Glucose handling

—

Glycemic improvement; rare hyperglycemia from glucagon component

Pancreatitis risk

—

Class warning

Thyroid C-cell tumours

—

Class warning (presumed)

Pregnancy / OB

—

Avoid (insufficient data)

Absolute Contraindications

Dihexa

·Not approved for human use — research compound only

Retatrutide

·MTC personal or family history (presumed class effect)
·Pregnancy / breastfeeding

Relative Contraindications

Dihexa

·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)

Retatrutide

·Severe gastroparesis
·History of pancreatitis
·Severe cardiovascular disease (HR signal)

05Administration Protocol

Parameter

Dihexa

Retatrutide

1. Human administration

No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.

Investigational peptide. Research vials reconstituted with bacteriostatic water per label.

2. Legal status

Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.

SQ — abdomen, thigh, or upper arm. Rotate weekly.

3. Timing

—

Once weekly, same day.

4. Storage

—

Refrigerate 2–8 °C. Light-protected.

5. Needle

—

27–31G, 4–8 mm insulin syringe.