Retatrutide: Triple Agonist for Weight Loss

FDA APPROVAL PENDING

This triple GIP/GLP-1/glucagon agonist produced up to 24-29% body weight loss in trials, alongside liver fat, kidney, and cardiovascular improvements.

Preclinical

Weight

Metabolic

GLP-3

Triple Receptor Agonist | Obesity & Metabolic Disease

Learn more

Weight

GLP-3

Metabolic

Amino acid sequence

40

Amino acids

4731.33da

Molecular weight

Peptide

Type

GLP-3 (LY3437943) is a 39-amino-acid synthetic peptide that simultaneously agonizes GLP-1, GIP, and glucagon receptors. By targeting all three receptors, it drives superior weight loss compared to single or dual incretin therapies, with Phase 2 trials showing up to 24.2% body weight reduction at 48 weeks. It is being evaluated in Phase 3 TRIUMPH trials for obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease.

Top researched benefits

Phase II Obesity Trial

Landmark RCT in 338 participants showing dose-dependent weight loss; 12mg dose achieved 24.2% reduction—highest recorded for any obesity medication. NEJM.

Phase II Type 2 Diabetes Study

Trial in 281 participants with type 2 diabetes: 16.9% weight loss and HbA1c reductions up to 2.16%. The Lancet.

GLP-3 Body Targets

The areas of the body that GLP-3 primarily affects.

2

Body Targets

GLP-3

Metabolic

Research targets include lipid metabolism pathways, insulin signaling, and energy homeostasis.

Gut

Research targets include gastrointestinal mucosal integrity, digestive signaling, and the gut-brain axis.

GLP-3 Targeted areas

Overview of GLP-3

GLP-3 activates GLP-1 and GIP receptors to increase insulin secretion, reduce gastric emptying, and enhance satiety, while concurrent glucagon receptor agonism elevates energy expenditure and promotes lipolysis. The hyperglycemic effect of glucagon receptor activation is counterbalanced by GLP-1 and GIP receptor-mediated insulinotropic activity, yielding a net anabolic-sparing, fat-oxidizing metabolic state.

weight loss

  • Clinical trials show 17.5% weight loss at 24 weeks and 24.2% at 48 weeks.
  • Continuous weight loss with no plateau at 48 weeks suggests greater long-term potential.
  • Addresses obesity through appetite suppression, energy expenditure, and metabolic efficiency.

type 2 diabetes

  • HbA1c reductions up to 2.16% with 82% achieving target levels below 6.5%.
  • Balanced glycemic control with minimal hypoglycemia risk.
  • Marked improvements in sensitivity with potential for reduced exogenous insulin requirements.

cardiovascularmetabolic

  • Non-HDL cholesterol reductions up to 26.9%, triglyceride reductions up to 40.6%.
  • Consistent decreases in systolic and diastolic blood pressure across trials.
  • Up to 82% reduction in liver fat with normalization in 90% of participants.

Research Dose (Reference)

Starting 2mg weekly, escalating to 4–12mg weekly

Research Frequency (Reference)

once weekly

Research Cycle (Reference)

Titrated over 12 weeks to maintenance dose; studied up to 48–68 weeks

Storage

Lyophilized: -20°C or below, protected from light. Reconstituted: 2–8°C for up to 28 days; do not freeze reconstituted solution.

Chemical Makeup

Key benefits

Produces up to 24–29% total body weight reduction over 48–68 weeks, exceeding efficacy of existing single and dual incretin therapies

Reduces visceral and hepatic fat, with Phase 2a data showing significant improvements in liver steatosis in MASLD patients

Lowers HbA1c in a dose-dependent manner, improving glycemic control in patients with type 2 diabetes and obesity

Improves kidney function markers, with the 12mg dose reducing urinary albumin by up to 31.5% in Phase 2 participants

Community interest

This peptide is still gaining traction in the community.

Triple Receptor Agonist | Obesity & Metabolic Disease

This overview is informational and based on aggregated descriptions from studies and user reports.

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GLP-3 Molecular Information

View the scientifc details of GLP-3.

40

Amino Acids

GLP-3

His

His

Position 1

Sec

Sec

Position 2

Glu

Glu

Position 3

Gly

Gly

Position 4

Thr

Thr

Position 5

Phe

Phe

Position 6

Thr

Thr

Position 7

Ser

Ser

Position 8

Asp

Asp

Position 9

Val

Val

Position 10

Ser

Ser

Position 11

Ser

Ser

Position 12

Tyr

Tyr

Position 13

Leu

Leu

Position 14

Glu

Glu

Position 15

Gly

Gly

Position 16

Gln

Gln

Position 17

Ala

Ala

Position 18

Ala

Ala

Position 19

Lys

Lys

Position 20

Glu

Glu

Position 21

Phe

Phe

Position 22

Ile

Ile

Position 23

Ala

Ala

Position 24

Trp

Trp

Position 25

Leu

Leu

Position 26

Val

Val

Position 27

Arg

Arg

Position 28

Gly

Gly

Position 29

Arg

Arg

Position 30

Gly

Gly

Position 31

Pro

Pro

Position 32

Ser

Ser

Position 33

Ser

Ser

Position 34

Gly

Gly

Position 35

Ala

Ala

Position 36

Pro

Pro

Position 37

Pro

Pro

Position 38

Pro

Pro

Position 39

Ser

Ser

Position 40

Amino acid sequence
HistidinePosition 1
SelenocysteinePosition 2
Glutamic acidPosition 3
GlycinePosition 4
ThreoninePosition 5
PhenylalaninePosition 6
ThreoninePosition 7
SerinePosition 8
Aspartic acidPosition 9
ValinePosition 10
SerinePosition 11
SerinePosition 12
TyrosinePosition 13
LeucinePosition 14
Glutamic acidPosition 15
GlycinePosition 16
GlutaminePosition 17
AlaninePosition 18
AlaninePosition 19
LysinePosition 20
Glutamic acidPosition 21
PhenylalaninePosition 22
IsoleucinePosition 23
AlaninePosition 24
TryptophanPosition 25
LeucinePosition 26
ValinePosition 27
ArgininePosition 28
GlycinePosition 29
ArgininePosition 30
GlycinePosition 31
ProlinePosition 32
SerinePosition 33
SerinePosition 34
GlycinePosition 35
AlaninePosition 36
ProlinePosition 37
ProlinePosition 38
ProlinePosition 39
SerinePosition 40

Molecular Weight

4731.33Da

Chain Length

40Amino Acids

Type

Peptide

GLP-3 Protocols

Subcutaneous injection is the only clinically documented route for GLP-3, administered once weekly in the abdomen, outer thigh, or upper arm. The protocol follows a gradual dose-escalation titration schedule starting at 1–2 mg per week to minimize GI side effects before reaching a maintenance dose of 4–12 mg weekly.

1000 mcg

Escalation

Establish GI tolerability before advancing to therapeutic dose

SubQ

1 week range

12000 mcg

High Maintenance

Maximize weight loss in patients who plateau at lower doses — up to 24% body weight reduction observed in Phase 2

SubQ

1 week range

4000 mcg

Low Maintenance

Sustain initial weight loss and appetite suppression at a well-tolerated dose

SubQ

1 week range

8000 mcg

Mid Maintenance

Achieve full therapeutic weight loss response in the primary efficacy range

SubQ

1 week range

4000 mcg

Glycemic Control

Reduce HbA1c and achieve euglycemia in Type 2 diabetes alongside weight reduction

SubQ

1 week range

12000 mcg

Cardiovascular Risk Reduction

Reduce cardiometabolic risk factors including visceral fat, triglycerides, and hepatic steatosis at maximum studied dose

SubQ

1 week range

GLP-3 Reconstitution Guide

Learn how to reconstitute GLP-3

Materials needed

Insulin syringes (0.5–1 mL, 29–31 gauge) for injection

3–5 mL syringe with 18–23 gauge needle for drawing BAC water

Bacteriostatic water (BAC water), 2 mL per 10 mg vial

Alcohol swabs

Retatrutide lyophilized powder vial (5 mg, 10 mg, 20 mg, or 30 mg)

1

Calculate your target concentration before reconstitution — a standard setup is 2 mL bacteriostatic water per 10 mg vial yielding 5 mg/mL

2

Wash hands thoroughly with soap and water for at least 20 seconds

3

Wipe the rubber stopper of both the peptide vial and BAC water vial with separate alcohol swabs and allow to dry for 10–15 seconds

4

Draw the required volume of bacteriostatic water into a 3–5 mL syringe using an 18–23 gauge needle

5

Insert the needle into the Retatrutide vial and slowly inject the BAC water down the inside glass wall of the vial over 10–20 seconds — never squirt directly onto the powder

6

Remove the syringe and gently swirl the vial in a circular motion until fully dissolved (1–3 minutes) — do not shake

7

Inspect the solution under light — it should be clear and colorless; discard if cloudy, discolored, or particulate matter is visible

8

Label the vial with the peptide name, concentration, reconstitution date, and 28-day expiry date

9

Refrigerate immediately at 2–8°C (36–46°F) and allow the vial to come to room temperature for 5–10 minutes before each injection

10

Draw the calculated dose volume into an insulin syringe, clean the injection site with an alcohol swab, pinch the skin, and inject at a 45–90° angle subcutaneously

11

Rotate injection sites each week between the abdomen (2+ inches from navel), outer thigh, and back of upper arm to prevent lipohypertrophy

GLP-3 Cycle

The GLP-3 Cycle section explains how long a typical cycle lasts and what research data suggests about each phase. In research contexts, biological systems may show reduced responsiveness with continuous exposure.

Research protocols often include washout periods between cycles to study baseline recovery and maintain experimental validity.

Week 1-2
Initial appetite suppression and mild GI effects as body adapts to triple hormone activation
Week 2-4
Noticeable food cravings reduction and portion size decrease; early weight loss (2-5%)
Week 4-8
Significant appetite control and steady weight loss (5-10%); improved glucose control
Week 8-16
Substantial weight reduction (10-18%) with enhanced energy expenditure
Week 16-24
Major weight loss milestone (15-22%) with cardiovascular benefits and liver fat reduction
Week 24-48
Maximum clinical efficacy (20-24.2%) with comprehensive metabolic improvements

Dosing tools

GLP-3 Peptide Dosage Calculator

Calculate peptide doses with our visual syringe guide.

mg

Enter the total amount of peptide in the vial in milligrams (as stated on the label).

The research quantity per administration, in mcg or mg.

1,000 mcg = 1 mg

1 mL

2 mL

3 mL

5 mL

Custom

Volume of bacteriostatic water you add to reconstitute the powder. Use BAC water for preservation.

Injection Results

Based on your vial and dilution inputs.

GLP-3

SINGLE COMPOUND

Volume per draw

0.05

mL

Concentration

10.00

mg/mL

Draws per vial

20

draws

Total draws per vial

20 draws

How it works

Based on a 10 mg GLP-3 vial diluted with 1 mL of bacteriostatic water, each 500 mcg research quantity equals 0.05 mL.

1mL / 100 units

5 units

0.050 mL

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Reference Guide

Dosing Cycle

Peptide
GLP-3
Dosing
Starting 2mg weekly, escalating to 4–12mg weekly
Dosing Frequency
once weekly
Cycle Duration
Titrated over 12 weeks to maintenance dose; studied up to 48–68 weeks
Storage
Lyophilized: -20°C or below, protected from light. Reconstituted: 2–8°C for up to 28 days; do not freeze reconstituted solution.

Note: Triple agonist; microdose for fewer side effects

Reconstitution Tips

  • Use bacteriostatic water (BAC)contains 0.9% benzyl alcohol for preservation in research solutions
  • Add liquid slowly during reconstitutionaim down the vial wall, not directly onto lyophilized powder
  • Never shakegently swirl or roll the vial until fully dissolved
  • Store properlyrefrigerate reconstituted solutions at 2–8°C
  • Use within 28 daysmost reconstituted peptides remain stable for approximately 4 weeks
  • Maintain sterilityclean vial septa with alcohol swabs before each draw

Peptide Interactions

Research suggestions of GLP-3 interactions with other common peptides and substances.

Healing

bpc

Longevity

BPC-157

COMPATIBLE

Safe combination; BPC-157 may provide GI protective benefits during retatrutide use.

COMPATIBLE

Weight

cag

Metabolic

Cagrilintide

MONITOR

Both cause significant GI effects. Not recommended without specialist supervision.

MONITOR

Weight

GLP-1

Metabolic

GLP-1

AVOID

Do not combine—overlapping GLP-1 agonist mechanisms increase severe hypoglycemia risk.

AVOID

Weight

GLP-2

Metabolic

GLP-2

AVOID

Do not combine with other dual/triple agonists—risk of severe hypoglycemia and excessive GI effects.

AVOID

Side effects

Avoid combining in research: Research combining GLP-3 with GLP-1, GLP-2.

Monitor in research: Exercise caution when studying GLP-3 with Cagrilintide.

Contraindications

Personal or family history of medullary thyroid carcinoma

MEN2 syndrome

Severe renal impairment

Stop signs

Severe persistent nausea or vomiting preventing adequate nutrition

Signs of pancreatitis: severe abdominal pain radiating to back

Severe hypoglycemia symptoms: confusion, dizziness, sweating

Excessive weight loss (>3 lbs per week consistently or >25% total body weight)

Gallbladder problems: severe right upper abdominal pain

Bad signs

Rapid tolerance or effectiveness loss suggests degraded or counterfeit productUnusual side effect profile may indicate contamination
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GLP-3Research References

GLP-3 is a preclinical compound

4Research references

GLP-3

GLP-3 is a preclinical compound

Phase II Obesity Trial

Landmark RCT in 338 participants showing dose-dependent weight loss; 12mg dose achieved 24.2% reduction—highest recorded for any obesity medication. NEJM.

2023

Phase II Type 2 Diabetes Study

Trial in 281 participants with type 2 diabetes: 16.9% weight loss and HbA1c reductions up to 2.16%. The Lancet.

2023

MASLD Substudy

Metabolic dysfunction-associated steatotic liver disease study: 82% liver fat reduction with normalization in >90% at highest doses. Nature Medicine.

2024

Structural Insights into Triple Agonism

Cryo-EM structures reveal simultaneous activation of GLP-1R, GIPR, and GCGR, explaining superior clinical efficacy. Cell Discovery.

2024

Frequently asked questions

What is a peptide dosage calculator?

A peptide dosage calculator is a free tool that converts your vial size, bacteriostatic water volume, and target dose into an exact syringe draw volume. Instead of doing the reconstitution math by hand, you enter three inputs and instantly get the concentration of your solution and how many milliliters or syringe units to draw. This calculator works for single peptide compounds and multi-peptide blends.

How do I calculate peptide dosage from a vial?

To calculate your peptide dose, divide the total peptide content of your vial in micrograms by the volume of bacteriostatic water you added in milliliters. This gives you your solution concentration in mcg/mL. Then divide your target dose by that concentration to get your draw volume. For example, a 5mg (5,000 mcg) vial reconstituted with 2mL of BAC water gives a concentration of 2,500 mcg/mL. A 250 mcg dose would require drawing 0.1mL. This calculator automates all of those steps instantly.

How much Bacteriostatic water should I add to a peptide vial?

Most people add 2mL to 3mL of bacteriostatic water per vial, but the right amount depends on the dose you want to draw and the syringe size you are using. Adding 1mL to a 5mg vial gives you a concentration of 5,000 mcg/mL, making each dose very small in volume. Adding 2mL gives you 2,500 mcg/mL, which is easier to measure on a standard insulin syringe. A general guideline is to choose a volume that puts your typical dose somewhere between 10 and 30 units on a U-100 syringe. Use the calculator above to test different water volumes and find what works for your dose.

How are peptides different from proteins?

Both are made of amino acids, but peptides are much smaller than proteins. Because of their tiny size, peptides can act like tiny messengers in the body, sending specific signals to your cells to tell them exactly what to do.​

Calculate peptide research quantities

Reference our peptide dosage, blend, and accumulation calculators for research purposes. Enter vial size, reconstitution volume, and target research quantity to calculate draw volumes instantly. For research use only — not administration or dosing guidance of any kind.