Side-by-side · Research reference

IGF-1 LR3vsTesofensine

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

AAnimal-StrongHUMAN-REVIEWED10/58 cited

BPhase 3AUTO-DRAFTED10/40 cited

IGF-1 LR3

IGF-1 Analogue · Research

3–10×Potency vs IGF-I

Low IGFBPBinding affinity

ResearchStatus

Research only · SQ typical in animal models

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

IGF-1 LR3

Tesofensine

Primary target

IGF-1 receptor (IGF-1R)McTavish 2009

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

Pathway

IGF-1R → IRS-1 → PI3K/Akt → Cell proliferation, protein synthesis, anti-apoptosisMuhlbradt 2009

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

Downstream effect

Enhanced cell proliferation, muscle anabolism, inhibition of apoptosis, increased telomerase activity

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

No — exogenous IGF analogue bypasses GH-mediated regulation

—

Origin

Synthetic 83-AA analogue: 13-AA N-terminal extension + Arg substitution at position 3

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

Antibody development

—

02Dosage Protocols

Parameter

IGF-1 LR3

Tesofensine

Research dose (animal models)

Variable by protocol and species

In vivo murine atherosclerosis studies used sustained delivery.

—

In vitro typical concentration

10–1000 ng/mLThomas 2007

Dose-dependent effects on follicle growth and estradiol production.

—

Half-maximal stimulation

0.6 nM LR3 vs 1.5 nM native IGF-1Price 2004

2.5-fold greater potency in lung fibroblast proliferation.

—

Evidence basis

Animal / in vitro only

Phase 2b + ongoing Phase 3Astrup 2008

Human use

Not FDA-approved; no published human trials

—

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)

03Metabolic / Fat Loss Evidence

Parameter

IGF-1 LR3

Tesofensine

Mechanism

IGF-1R activation → lipolytic signaling; secondary to anabolic effects

—

Direct lipolytic evidence

Minimal — primarily anabolic/anti-apoptotic in literature

—

Atherosclerotic plaque effects

Reduced stenosis and core size in ApoE-KO micevon 2011

Plaque stabilization via vSMC phenotype modulation, not direct fat loss.

—

Human data

None published

—

04Side Effects & Safety

Parameter

IGF-1 LR3

Tesofensine

Hypoglycemia risk

Theoretical — IGF-1 analogues can lower blood glucose

—

Excessive cell proliferation

Mitogenic signaling; theoretical tumor promotion risk

—

Telomerase activation

2–10-fold increase in prostate cancer cells (PC-3, DU-145, LAPC-4)Wetterau 2003

Critically involved in cancer cell immortalization.

—

Oocyte degeneration

Increased oocyte degeneration at high doses (≥1000 ng/mL) in bovine folliclesThomas 2007

—

Unregulated anabolism

Bypasses physiological GH/IGF-1 feedback; no pulsatility control

—

Unknown human safety profile

No published human trials; safety data absent

—

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

IGF-1 LR3

·Active malignancy or history of cancer
·Not approved for human use

Tesofensine

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

Relative Contraindications

IGF-1 LR3

·Diabetes or glucose intolerance
·Family history of cancer

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

IGF-1 LR3

Tesofensine

1. Research use only

IGF-1 LR3 is not FDA-approved for human use. All administration data derives from animal or in vitro studies.

Oral capsule (investigational; not commercial).

2. Typical research route

Subcutaneous or intraperitoneal injection in animal models. In vitro: added directly to culture medium at concentrations of 10–1000 ng/mL.Thomas 2007

Swallow whole with water, morning only.

3. Reconstitution (research)

Lyophilised powder reconstituted in sterile water or buffered saline per manufacturer protocol. Store at 2–8 °C after reconstitution.

Morning to mitigate insomnia. Do not dose evening.

4. Stability

Enhanced stability vs native IGF-1 due to reduced IGFBP binding; exact half-life in vivo not fully characterized in humans.

Room temp ≤25 °C, dry place.

5. Caveat

—

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

06Stack Synergy

IGF-1 LR3

+ GHRP-6

Multi-pathway

View GHRP-6 →

GHRP-6 stimulates endogenous GH release, which drives hepatic IGF-1 synthesis. IGF-1 LR3 provides exogenous, IGFBP-resistant IGF signaling. Combining upstream GH stimulation with downstream IGF receptor activation creates a dual-pathway anabolic effect. However, this bypasses natural feedback and carries compounded mitogenic risk.

GHRP-6: 100–200 mcg SQ · 2–3× daily
IGF-1 LR3: Research doses variable · post-workout typical in animal models
Note: Research context only — no human protocols exist
Primary benefit: Theoretical maximal anabolic signaling (GH + IGF axes)

+ Ipamorelin

Multi-pathway

View Ipamorelin →

Ipamorelin (selective GHRP) stimulates pulsatile GH release without cortisol/prolactin elevation. IGF-1 LR3 directly activates IGF-1R independent of GH. This stack targets both upstream (GH secretion) and downstream (IGF receptor) nodes but eliminates physiological feedback, raising safety concerns around unchecked proliferation.

Ipamorelin: 200–300 mcg SQ · evening
IGF-1 LR3: Research doses only · timing variable
Caution: No human data; animal/in vitro only
Primary benefit: Dual-axis anabolic signaling (theoretical)

Tesofensine

— no documented stacks