Side-by-side · Research reference

GLP-1 (7-37)vsTesofensine

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

AHuman-MechanisticHUMAN-REVIEWED16/43 cited

BPhase 3AUTO-DRAFTED10/40 cited

GLP-1 (7-37)

Incretin Hormone · Native Peptide

~2 minHalf-lifeAlavi 2021 Ding 2017

3297.7 DaMolecular weightAlavi 2021

1922Discovery year

Research use only · IV/SC in experimental settings

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

GLP-1 (7-37)

Tesofensine

Primary target

GLP-1 receptor (class B GPCR)Koole 2015

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

Pathway

GLP-1R activation → cAMP production → PKA signaling → insulin secretion (pancreatic β-cells)Lu 2025 Koole 2015

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

Downstream effect

Glucose-dependent insulin release, glucagon suppression, delayed gastric emptying, reduced food intakeLu 2025 Ding 2017

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

Yes — physiological secretion and degradation preserved

—

Origin

Endogenous peptide cleaved from proglucagon in intestinal L cells; secreted postprandially

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

Antibody development

—

02Dosage Protocols

Parameter

GLP-1 (7-37)

Tesofensine

Clinical use

None — native GLP-1 not used therapeutically

Engineered analogues (semaglutide, liraglutide) used clinically.Friedman 2024

—

Research dosing

Variable — 0.1–10 nmol/kg in animal models

Used as reference standard for analogue comparison.

—

Half-life

~2 minutes (plasma)Alavi 2021 Ding 2017

Requires continuous infusion for sustained effect.

~9 days (very long)

Modified analogues

t½ extended to 13 h (liraglutide), 165 h (semaglutide)

Via DPP-4 resistance + fatty acid acylation.

—

Standard dose

—

0.25–0.5 mg / dayAstrup 2008

Frequency

—

Once daily, morning

Lower / starter dose

—

0.125 mg / day

Evidence basis

—

Phase 2b + ongoing Phase 3Astrup 2008

Duration

—

24 weeks per studied cycle

Form

—

Oral capsule

Timing

—

Morning to avoid sleep disruption

03Metabolic / Fat Loss Evidence

Parameter

GLP-1 (7-37)

Tesofensine

Mechanism

GLP-1R activation in hypothalamic satiety centers (arcuate nucleus) reduces food intakeLu 2025

Effect demonstrated with long-acting analogues (liraglutide).Lu 2025

—

Native GLP-1 efficacy

Minimal — rapid degradation prevents sustained appetite suppression

—

Gastric emptying

Delayed in animal models, contributing to satiety

—

Body weight impact

Not observed with native GLP-1 — requires analogue formulations

—

04Side Effects & Safety

Parameter

GLP-1 (7-37)

Tesofensine

Native GLP-1

Well-tolerated in research settings; no prolonged exposure data

—

Hypoglycemia risk

Low — insulin secretion is glucose-dependent

—

Analogue side effects

Nausea, vomiting, diarrhea (GLP-1R agonists)

Not applicable to native GLP-1 due to non-therapeutic use.

—

GLP-1 resistance

High glucose-induced PKCβ overexpression may reduce GLP-1 responsiveness in endothelial cellsPujadas 2016

—

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

GLP-1 (7-37)

—

Tesofensine

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

Relative Contraindications

GLP-1 (7-37)

—

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

GLP-1 (7-37)

Tesofensine

1. Research use only

Native GLP-1(7-37) is not formulated for therapeutic use. Administered IV or SC in experimental protocols to study GLP-1R pharmacology and as reference standard for analogue development.

Oral capsule (investigational; not commercial).

2. Storage

Lyophilised peptide stored at -20°C or below. Reconstituted solutions should be prepared fresh and used immediately due to rapid degradation.

Swallow whole with water, morning only.

3. Clinical alternatives

For therapeutic GLP-1R activation, use FDA-approved long-acting analogues: semaglutide (once weekly), liraglutide (once daily), dulaglutide (once weekly), or exenatide (twice daily or once weekly).

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.