Side-by-side · Research reference

GLP-1 (7-37)vsRetatrutide

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 2HUMAN-REVIEWED10/41 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

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

GLP-1 (7-37)

Retatrutide

Primary target

GLP-1 receptor (class B GPCR)Koole 2015

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

Pathway

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

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

Downstream effect

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

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

Feedback intact?

Yes — physiological secretion and degradation preserved

—

Origin

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

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

Antibody development

—

02Dosage Protocols

Parameter

GLP-1 (7-37)

Retatrutide

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.

~6 days (estimated from class)

Modified analogues

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

Via DPP-4 resistance + fatty acid acylation.

—

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

Evidence basis

—

Phase 2 trial; Phase 3 ongoingJastreboff 2023

Duration

—

Indefinite for chronic indication (presumed)

Reconstitution

—

Investigational; not commercially available

Timing

—

Any time of day

03Metabolic / Fat Loss Evidence

Parameter

GLP-1 (7-37)

Retatrutide

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)

Retatrutide

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

—

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

GLP-1 (7-37)

—

Retatrutide

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

Relative Contraindications

GLP-1 (7-37)

—

Retatrutide

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

05Administration Protocol

Parameter

GLP-1 (7-37)

Retatrutide

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.

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

2. Storage

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

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

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).

Once weekly, same day.

4. Storage

—

Refrigerate 2–8 °C. Light-protected.

5. Needle

—

27–31G, 4–8 mm insulin syringe.