GLP-1 & metabolic · Investigational obesity and type 2 diabetes (Phase 3)

Retatrutide

LY3437943, GLP-1/GIP/glucagon triple agonist

Lilly’s GLP-1 / GIP / glucagon triple agonist. The literature rates 90/100 on trial data, not on a licence. GI effects are dose-dependent. Transient heart-rate rise is in the file.

Library entry →

Appetite
Glycaemic control
Weight (trial data)

Catalog fill: 10 mg
Typical water: 2 mL
Route: Subcutaneous, once weekly
Cycle: Titration over months. Do not jump to a top-end amount in week one.
Approval: Phase 3 (TRIUMPH). Not FDA-approved.
Status: Investigational. Not approved.
Evidence: Phase 2 in NEJM; Phase 3 ongoing.
Research score: 90 / 100

Mechanism

GLP-1: glucose-dependent insulin, less glucagon, satiety. GIP: insulin sensitivity. Glucagon receptor: energy expenditure. All three at once.

Safety file

Incretin-like GI effects (nausea, diarrhoea). Transient heart-rate increase. Profile is still being written in Phase 3.

Nausea
Vomiting
Diarrhoea
Decreased appetite
Injection-site reactions

Reconstitution

2 mL bacteriostatic water into 10 mg gives 5 mg/mL. A 2.5 mg weekly amount is 50 units. A 30 mg vial at the same concentration takes 6 mL.

Research amounts

Once weekly, same day, abdomen or thigh. Titrate slowly.

Step	Amount	Frequency	Notes
Start	2 mg	Weekly	40 units at 5 mg/mL
Step	4 mg	Weekly	80 units — consider a more dilute reconstitution if the draw is awkward
Later research amounts	8–12 mg	Weekly	Reconstitute a larger vial, or a larger water volume, so the draw stays on the syringe

Storage

Lyophilized: −20 °C freezer preferred; a refrigerator is also acceptable. Do not open a cold vial — wait 15–30 minutes so it does not sweat. Avoid freeze–thaw cycling.
After water: 2–8 °C, dark, up to 45 days when mixed with bacteriostatic water. Mixed vials stay in their box. Sterile water (no preservative) is single-use.

Worksheet notes

Gastrointestinal effects scale with the size of the jump, not just the absolute amount.
This compound is an investigational metabolic agonist. The worksheet does not diagnose, treat, or replace a clinician.
Bacteriostatic water: 20–25 °C. Do not refrigerate the diluent.
Amounts on this sheet are reconstitution math for the vial, not a recommendation.

Full protocol

Titration, schedule, and handling

The complete protocol for Retatrutide. Where it differs from the worksheet amounts above, the worksheet reflects the NovaEvum vial.

Important: Reconstitute with bacteriostatic water only. Do not use sodium chloride (saline) bacteriostatic water. The wrong diluent can ruin the entire vial.

Reconstitution

Concentration by vial size and water volume
Vial	1 mL water	2 mL water	3 mL water
10 mg	10 mg/mL	5 mg/mL	3.33 mg/mL
30 mg	30 mg/mL	15 mg/mL	10 mg/mL
60 mg	60 mg/mL	30 mg/mL	20 mg/mL

Works with anywhere from 1 mL to 3 mL of bacteriostatic water. Less water makes a stronger solution with smaller draws; more water dilutes it for larger, easier-to-measure draws. Always bacteriostatic water, never saline.

Use bacteriostatic water as the diluent.
Add the water slowly, letting it run down the inside wall of the vial rather than onto the powder.
Swirl gently to mix, then leave it to dissolve. Do not shake.
Give it a few minutes. The finished solution should be clear and colourless.

Protocol

Route: Subcutaneous

Standard titration (once weekly, subcutaneous)

Weeks 1 to 4: 2 mg once weekly
Weeks 5 to 8: 4 mg
Weeks 9 to 12: 6 mg
Weeks 13 to 16: 9 mg
Week 17 onward: 12 mg as the target maintenance dose
Hold each dose for the full 4 weeks before going up

If you do not need the full dose

Many people get strong results and stop climbing at 6 mg or 8 mg
There is no rule that you have to reach 12 mg
Stay at the lowest dose that is still working for you

Dosing detail

Start at 2 mg. In the trials, people who jumped straight to higher doses had far more nausea (around 60%) than those who started low (around 17%), so the slow ramp is the whole point, not a formality.
The newer Phase 3 schedule (above) ramps 2, 4, 6, 9, 12 mg, each held 4 weeks, for the smoothest climb. The older Phase 2 trial jumped 2, 4, 8, 12 and skipped the 6 and 9 mg steps, which works but trades tolerability for speed.
Working range is roughly 4 mg to 12 mg weekly. 12 mg was the highest dose studied and gave the most weight loss.
Pick one day a week and keep it consistent, since the half-life is about 6 days.

Duration

Run it in 4-week blocks while titrating. Full programs run 16 to 24 weeks or longer. Many taper the dose down at the end rather than stopping cold, since stopping abruptly tends to bring weight back.

Notes

Inject subcutaneously into the stomach, love handles or thigh, rotating the site each week.
GI effects (nausea, early fullness, occasional constipation) hit most in the first week of a new dose and usually settle.
Keep protein intake high and stay hydrated as appetite drops, to hold onto muscle.
Splitting the weekly dose into two smaller shots smooths out side effects for some people.

Storage and handling

Keep the powdered (lyophilized) vial in a cool, dark place. Refrigerate it for longer-term storage before mixing.
Once reconstituted and refrigerated at 2–8 °C away from light, use the vial within 90 days.
Do not freeze a reconstituted vial, and keep it away from heat and sunlight.
If the solution turns cloudy, develops floating particles, or shows any other sign of degradation, stop using that vial.