Side-by-side · Research reference

DihexavsTesofensine

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 3AUTO-DRAFTED10/40 cited

Dihexa

Angiotensin IV Analogue · Pre-Clinical

Pre-clinicalDevelopment stage

Rodent onlyEvidence basisBenoist 2014

HGF/c-MetTarget systemWright 2015

Not established — animal studies only

Tesofensine

SNDRI · Phase 3 obesity candidate

0.25–0.5 mgDaily doseAstrup 2008

9.2 kgWeight ↓ (24 wk)Astrup 2008

Phase 3Evidence levelAstrup 2008

Oral · Once daily morning

01Mechanism of Action

Parameter

Dihexa

Tesofensine

Primary target

c-Met receptor (HGF receptor tyrosine kinase)

Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008

Pathway

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

Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008

Downstream effect

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

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

—

Origin

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

Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008

Antibody development

—

02Dosage Protocols

Parameter

Dihexa

Tesofensine

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 2b + ongoing Phase 3Astrup 2008

Clinical status

No Phase 1, 2, or 3 trials published

—

Standard dose

—

0.25–0.5 mg / dayAstrup 2008

Frequency

—

Once daily, morning

Lower / starter dose

—

0.125 mg / day

Duration

—

24 weeks per studied cycle

Form

—

Oral capsule

Timing

—

Morning to avoid sleep disruption

Half-life

—

~9 days (very long)

04Side Effects & Safety

Parameter

Dihexa

Tesofensine

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

—

Heart rate / BP

—

Dose-dependent ↑ HR + BPAstrup 2008

Insomnia

—

Dose-related; mitigate with morning timing

Dry mouth

—

Common

Nausea

—

Common

Mood changes

—

Anxiety / agitation possible

Cardiovascular events

—

Phase 3 trial monitoring; not yet FDA-cleared

Pregnancy / OB

—

Contraindicated

Absolute Contraindications

Dihexa

·Not approved for human use — research compound only

Tesofensine

·Pregnancy / breastfeeding
·Severe cardiovascular disease
·Concurrent MAOI use

Relative Contraindications

Dihexa

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

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

Dihexa

Tesofensine

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.

Oral capsule (investigational; not commercial).

2. Legal status

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

Swallow whole with water, morning only.

3. Timing

—

Morning to mitigate insomnia. Do not dose evening.

4. Storage

—

Room temp ≤25 °C, dry place.

5. Caveat

—

Monitor BP + HR + mood. Avoid stimulants + MAOIs.