Retatrutide Dosage Chart

Summary: Retatrutide is not FDA approved. The Phase 2 obesity protocol started at 2 mg weekly and doubled roughly every 4 weeks to a 12 mg maximum, with weight loss reaching 24.2% at 48 weeks in the top dose arm.

This content is for informational purposes only and is not medical advice. Always consult a qualified healthcare provider before starting, changing, or stopping any medication.

The Phase 2 obesity trial published by Jastreboff and colleagues in NEJM 2023 used a once-weekly subcutaneous injection. The protocol started at 2 mg, roughly doubled every 4 weeks, and capped at 12 mg [1]. That five-step ladder, 2 mg, 4 mg, 8 mg, 12 mg, is the schedule almost every clinical reference, peptide reconstitution chart, and self-administered protocol now traces back to.

Below is the full dose-by-week chart, the mg-to-mL-to-units conversion for the three concentrations you actually see in practice (5 mg/mL, 10 mg/mL, 20 mg/mL), the side-effect rates Lilly published at each dose, and how this schedule compares to FDA-approved tirzepatide.

The published Phase 2 dosing schedule

The NEJM 2023 trial randomized 338 adults with obesity to placebo or to one of several retatrutide arms. The arms that climbed the full ladder reached their maximum dose at week 13 and stayed there through week 48 [1].

WeeksWeekly dosePhase
1 to 42 mgInitiation
5 to 84 mgFirst escalation
9 to 128 mgSecond escalation
13 onward12 mgMaintenance (trial cap)

The published protocol had three additional arms that stopped escalating at 4 mg or 8 mg, so the trial reports weight loss data at 4 mg, 8 mg, and 12 mg as final maintenance doses, not only at the top of the ladder. The 1 mg dose was tested as a separate low-dose arm and is not part of the standard escalation path. Phase 3 TRIUMPH protocols use the same 2 to 12 mg structure [4].

The reconstitution math: mg, mL, and U-100 syringe units

Research-grade retatrutide ships as lyophilized powder in 5 mg, 10 mg, 15 mg, or 30 mg vials. You add bacteriostatic water yourself. The volume of water you add determines the concentration, which determines the syringe mark you draw to for any given milligram dose. Two formulas cover the whole problem.

mL per dose = mg desired / concentration (mg/mL)
units (U-100) = mL × 100

A U-100 insulin syringe is calibrated so 100 units equals 1 mL. That is the only kind of insulin syringe most pharmacies stock. The unit number on the barrel is the volume in mL times 100.

5 mg/mL concentration (common for 10 mg vials with 2 mL BAC water)

Weekly dosemL to drawU-100 syringe units
2 mg0.40 mL40 units
4 mg0.80 mL80 units
8 mg1.60 mL160 units (split across two injections or use larger syringe)
12 mg2.40 mL240 units (split required)

At 5 mg/mL the math is the friendliest for the starting dose. A single 1 mL insulin syringe handles 2 mg and 4 mg cleanly. Once you hit 8 mg you exceed the 1 mL syringe capacity and you either move to a larger syringe (2.5 mL or 3 mL), accept splitting the dose into two injections in one sitting, or reconstitute at a higher concentration.

10 mg/mL concentration (common for 10 mg vials with 1 mL BAC water)

Weekly dosemL to drawU-100 syringe units
2 mg0.20 mL20 units
4 mg0.40 mL40 units
8 mg0.80 mL80 units
12 mg1.20 mL120 units (just over one syringe)

10 mg/mL is the concentration most retatrutide community protocols default to because it keeps the entire 2 mg to 12 mg ladder inside a single 1 mL insulin syringe up through 10 mg. At 12 mg you still need to draw a second 20-unit push, but the math everywhere else is clean.

20 mg/mL concentration (common for 30 mg vials with 1.5 mL BAC water)

Weekly dosemL to drawU-100 syringe units
2 mg0.10 mL10 units
4 mg0.20 mL20 units
8 mg0.40 mL40 units
12 mg0.60 mL60 units

20 mg/mL is the densest reconstitution that still draws reliably through a 29 or 30 gauge insulin needle. The whole 2 to 12 mg ladder fits inside a single 1 mL syringe with room to spare. The trade-off is that small errors in syringe reading translate into larger absolute milligram swings. A 2-unit mis-draw at 5 mg/mL is 0.1 mg of retatrutide. The same 2-unit error at 20 mg/mL is 0.4 mg. For people just learning to draw, lower concentrations are more forgiving.

Dose-response: what each step on the ladder produces

The Phase 2 trial reported weight change from baseline at both 24 and 48 weeks. The numbers make the dose-response curve plain.

Maintenance doseWeight loss at 24 weeksWeight loss at 48 weeks
Placebo1.6%2.1%
1 mg7.2%8.7%
4 mg12.9%17.1%
8 mg15.7%22.8%
12 mg17.5%24.2%

The 12 mg arm at 48 weeks is the headline figure: 24.2% mean body weight reduction [1]. Every single participant in that group lost at least 5% of body weight. 93% lost 10% or more. 83% reached the 15% threshold. The Phase 3 TRIUMPH-4 readout extended the 12 mg arm to 68 weeks and produced 28.7% mean weight loss, the highest figure published for any incretin-class drug to date [4].

The 4 mg dose at 48 weeks (17.1%) already exceeds what tirzepatide 15 mg produced in SURMOUNT-1 (20.9% over 72 weeks adjusted to comparable timeframes is competitive at lower retatrutide doses). The glucagon-receptor activity is what most pharmacologists credit for the additional efficacy at the higher end of the curve, because glucagon raises resting energy expenditure in addition to the appetite suppression GLP-1 provides.

Side effects by dose

GI side effects rise with dose. The Phase 2 trial reported the following incidence rates at the highest week of the maintenance phase for each arm [1].

Side effect4 mg8 mg12 mgPlacebo
Nausea25%36%46%9%
Diarrhea22%28%34%11%
Vomiting8%10%13%2%
Constipation6%12%16%4%

Discontinuation for any reason was about 6% in the 12 mg arm, which is comparable to tirzepatide and semaglutide trials and suggests the symptoms were manageable for most participants who titrated through them. The dose-limiting symptoms cluster in the first two weeks after each step up, then settle. People who try to compress the schedule, jumping from 2 mg to 8 mg in one step for example, predictably suffer more.

One side effect specific to retatrutide is dose-dependent heart rate elevation, averaging 6 to 11 beats per minute at the 12 mg dose compared to placebo. This appears related to glucagon-receptor activity. Cardiac events in the Phase 2 trial were rare, but the heart rate signal is the reason Phase 3 protocols include closer cardiovascular monitoring than the semaglutide and tirzepatide trials required.

A separate signal worth knowing: a small subset of participants reported transient cutaneous hyperesthesia (skin sensitivity) at higher doses. The mechanism is unclear and the symptom resolved on its own or with dose pause. Phase 3 is tracking this prospectively.

How this compares to FDA-approved tirzepatide

Tirzepatide is the closest FDA-approved comparator, both because it shares the once-weekly subcutaneous schedule and because it acts on two of the three receptors retatrutide hits (GLP-1 and GIP, but not glucagon). The titration ladders are structurally similar.

PropertyRetatrutide (Phase 2 protocol)Tirzepatide (FDA Zepbound label)
Starting dose2 mg weekly2.5 mg weekly
Titration interval4 weeks per step4 weeks per step
Number of steps4 (2, 4, 8, 12)6 (2.5, 5, 7.5, 10, 12.5, 15)
Maximum dose12 mg weekly15 mg weekly
Time to maximumAbout 13 weeksAbout 21 weeks
Approval statusPhase 3 (TRIUMPH)FDA approved 2023
Mean weight loss at maximum dose24.2% at 48 weeks20.9% at 72 weeks

Tirzepatide's ladder uses 2.5 mg increments at the lower end and 2.5 mg increments at the top. Retatrutide's ladder doubles at each step until the cap, which is a steeper escalation per unit time but a shorter overall ramp. Both protocols share the 4-week minimum at each step. The Zepbound prescribing information specifically warns against escalating faster than every 4 weeks because the GI side effects of the GIP/GLP-1 mechanism are predictably worse with compressed titration [3]. The same logic applies, with even more weight, to retatrutide's glucagon-loaded receptor profile.

Microdosing and slower titrations

A loud subset of the research community runs retatrutide at sub-trial doses, often described as microdosing. Typical patterns are 0.5 mg twice weekly, 1 mg weekly held indefinitely, or stretching the 2 mg starting dose for 8 to 12 weeks before any escalation. The published Phase 2 data on the 1 mg arm (8.7% weight loss at 48 weeks) is what most microdosers cite to argue the lower end of the curve is still clinically meaningful with fewer GI symptoms.

The peer-reviewed evidence base for microdosing is thin. The 1 mg arm of the Phase 2 trial is the only published dose below 2 mg, and it was tested as a maintenance dose rather than as a stepping stone. There is no Lilly-published data on twice-weekly fractional dosing. The community-reported tolerance benefit is real but the long-term efficacy at sub-2 mg weekly equivalents is extrapolated, not measured.

The 2 mg starting dose in the standard protocol is itself low enough to function as a "microdose" for most people in their first month. If GI symptoms are the concern, the better-supported move is to stretch the 2 mg block from 4 weeks to 6 or 8 weeks before escalating, rather than to invent a sub-2 mg fractional schedule that has no trial data behind it.

Reconstitution and storage practicalities

Most retatrutide arrives as 5 mg, 10 mg, or 30 mg of lyophilized powder in a sealed glass vial. Bacteriostatic water (0.9% benzyl alcohol in sterile water) is the standard diluent. The amount of water you add determines your concentration and therefore your unit-per-mg math for the entire vial. Do this once, write the concentration on the vial with a permanent marker, and verify it before every draw.

A typical schedule for a 10 mg vial reconstituted to 10 mg/mL (1 mL of BAC water):

WeekDoseVolume drawnVial remaining
12 mg0.20 mL0.80 mL (8 mg)
22 mg0.20 mL0.60 mL (6 mg)
32 mg0.20 mL0.40 mL (4 mg)
42 mg0.20 mL0.20 mL (2 mg)
54 mg0.40 mLNew vial required

A reconstituted vial is stable refrigerated at 36 to 46 degrees Fahrenheit for 28 to 56 days according to the typical bacteriostatic water shelf life. Do not freeze it. The peptide degrades faster at room temperature.

Where this article ends and your prescriber begins

Everything above is the published Phase 2 protocol and the supporting math. None of it is a personal recommendation. Retatrutide is investigational. Anyone using it outside a clinical trial is doing so without regulatory cover and without the systematic adverse-event monitoring that exists in the TRIUMPH program. Decisions about whether to start, how fast to escalate, and when to stop belong to a relationship with a clinician who can monitor heart rate, kidney function, and the cardiometabolic markers the trial is tracking.

The Phase 3 readouts are expected through 2026 and 2027. If TRIUMPH replicates the Phase 2 efficacy and the dysesthesia and heart rate signals stay manageable, retatrutide will likely become the first FDA-approved triple agonist sometime in 2027. The prescribing label that follows will tighten the dosing schedule on this page, define exclusion criteria, and specify monitoring. Until then, this chart is the best summary of what Lilly's published trial actually did.

Common questions about retatrutide dosing

What is the standard retatrutide titration schedule?
2 mg weekly for 4 weeks, then 4 mg for 4 weeks, then 8 mg for 4 weeks, then 12 mg as the maintenance cap. This is the Phase 2 NEJM 2023 protocol and the TRIUMPH Phase 3 schedule.
How many units of retatrutide is 4 mg on an insulin syringe?
At 5 mg/mL it is 80 units. At 10 mg/mL it is 40 units. At 20 mg/mL it is 20 units. Units equal the mL volume times 100, and mL equals 4 divided by the vial concentration.
What is the retatrutide starting dose?
2 mg once weekly is the starting dose in every published Phase 2 and Phase 3 arm that follows the standard escalation. A 1 mg dose was studied separately but is not part of the standard titration ladder.
How often is retatrutide injected?
Once weekly, subcutaneously. The same day each week is best for consistency. Sites are abdomen, thigh, or upper outer arm. Rotate between weeks.
How long does it take to reach 12 mg?
12 weeks of titration plus the start of week 13 at the full dose. The schedule reaches maximum dose at week 13 if every step is the published 4 weeks.
Is 1 mg of retatrutide enough to lose weight?
The Phase 2 trial showed 8.7% mean weight loss at 48 weeks in the 1 mg arm. That is meaningful but well below the 24.2% the 12 mg arm produced. The dose-response curve is steep.
Can the retatrutide dose be increased faster than every 4 weeks?
The Phase 2 protocol used 4 weeks at each step because compressed escalation worsens nausea and vomiting. Faster titration has no published efficacy benefit and a clear tolerability cost.
How does retatrutide dosing compare to tirzepatide dosing?
Both start near 2 mg, both step every 4 weeks, both peak after about 3 to 5 months of titration. Retatrutide's ladder has 4 steps to 12 mg. Tirzepatide's ladder has 6 steps to 15 mg. Retatrutide produces more weight loss at peak in head-to-head comparable timepoints.
What is the maximum retatrutide dose?
12 mg once weekly. This is the highest dose with published efficacy and safety data. Doses above 12 mg have not been studied in any phase of the Lilly trial program.
Is microdosing retatrutide supported by trial data?
The 1 mg arm is the only sub-2 mg dose with published trial data. Fractional schedules below 1 mg or twice-weekly splits are community practices without peer-reviewed evidence of efficacy or safety at those patterns.

References

  1. Jastreboff AM et al, Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial, NEJM 2023
  2. Rosenstock J et al, Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes, Lancet 2023
  3. FDA Zepbound (tirzepatide) prescribing information
  4. ClinicalTrials.gov, TRIUMPH Programme, Eli Lilly retatrutide Phase 3