Side-by-side · Research reference

RetatrutidevsTesofensine

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

APhase 2Reviewed10/41 cited

BPhase 3Draft10/40 cited

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

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

Retatrutide

Tesofensine

Primary target

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

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

Pathway

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

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

Downstream effect

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

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

—

Origin

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

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

Antibody development

—

02Dosage Protocols

Parameter

Retatrutide

Tesofensine

Standard dose

12 mg / week (max efficacy)Jastreboff 2023

Phase 2 trial dose. Phase 3 dosing TBD.

0.25–0.5 mg / dayAstrup 2008

Frequency

Once weekly

Once daily, morning

Titration schedule

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

—

Evidence basis

Phase 2 trial; Phase 3 ongoingJastreboff 2023

Phase 2b + ongoing Phase 3Astrup 2008

Duration

Indefinite for chronic indication (presumed)

24 weeks per studied cycle

Reconstitution

Investigational; not commercially available

—

Timing

Any time of day

Morning to avoid sleep disruption

Half-life

~6 days (estimated from class)

~9 days (very long)

Lower / starter dose

—

0.125 mg / day

Form

—

Oral capsule

04Side Effects & Safety

Parameter

Retatrutide

Tesofensine

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)

Contraindicated

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

Absolute Contraindications

Retatrutide

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

Tesofensine

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

Relative Contraindications

Retatrutide

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

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

Retatrutide

Tesofensine

1. Reconstitution

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

Oral capsule (investigational; not commercial).

2. Injection site

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

Swallow whole with water, morning only.

3. Timing

Once weekly, same day.

Morning to mitigate insomnia. Do not dose evening.

4. Storage

Refrigerate 2–8 °C. Light-protected.

Room temp ≤25 °C, dry place.

5. Needle

27–31G, 4–8 mm insulin syringe.

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