Retatrutide Dosing Protocol: Injection, Pen Vial, Nasal Spray & Titration (2026)

Retatrutide Quick Start

Retatrutide is an investigational triple agonist that activates the GLP-1, GIP, and glucagon receptors. It is studied for weight management and metabolic outcomes and has produced large weight-reduction effects in trials. It is dosed weekly with a gradual titration to manage gastrointestinal side effects. It is investigational (Phase 3 as of 2026).

Quick reference Phase 3 (investigational)

Class

GLP-1 / GIP / glucagon triple agonist

Formats

Vial · Pen vial · Nasal spray

Research focus

Weight, metabolic

Schedule shape

Weekly, titrated

Vial size

10 mg · 30 mg

This guide is an educational research reference. It does not diagnose, treat, or prescribe, and is not medical advice. Consult a licensed clinician before considering any compound.

Retatrutide Dosing Protocols

The injectable (subcutaneous), pen-vial and nasal-spray formats are documented as separate protocols. Both follow the same weekly titration ladder — roughly four weeks per step — and can be run as a single weekly dose or split into two doses per week at the same weekly total. Splitting often smooths gastrointestinal side effects. These are research-planning references, not personal dosing recommendations.

Injection — Subcutaneous (U-100 units)

30 mg + 3 mL BAC → 10 mg/mL (vial max fill).

Phase	Weekly	1×/wk	2×/wk
1	2 mg	20 u	10 u ×2
2	4 mg	40 u	20 u ×2
3	8 mg	80 u	40 u ×2
4 (max)	12 mg	120 u*	60 u ×2

10 mg/mL · 1 mg = 10 units · *12 mg once-weekly = 1.2 mL (split draw)

Nasal Spray (0.6 mg / spray)

Pre-mixed nasal spray, ready to use.

Phase	Weekly	1×/wk	2×/wk
1	2 mg	4 sprays	2 ×2
2	4 mg	7 sprays	4 ×2
3	8 mg	14 sprays	7 ×2
4 (max)	12 mg	20 sprays	10 ×2

Each 0.1 mL spray delivers 0.6 mg

Pen Vial — Pre-Reconstituted 3 mL

Supplied already reconstituted to 3 mL — no mixing step. Doses are given in units, the scale a reusable pen dials in (300 units per vial). Pens step in whole or half units depending on the model — round any fractional figure to the nearest increment your device supports.

Phase	Per dose (units)	Delivers	2×/wk
1	20 units	2 mg	10 units ×2
2	40 units	4 mg	20 units ×2
3	80 units	8 mg	40 units ×2
4 (max)	120 units	12 mg	60 units ×2

30 mg in 3 mL → 100 mcg per unit · 300 units per pen · 1 mg = 10 units

The pen ships at exactly the 3 mL fill the injection protocol above already assumes, so the unit ladder is identical — the pen simply removes the mixing step.

At a 5 mL fill each spray delivers 0.6 mg, so spray doses round up to the next whole spray (e.g., 2 mg → 4 sprays); the 12 mg step lands exactly on 20 sprays. Spreading the dose over more sprays evens out per-actuation variability. The injection delivers any step precisely; the once-weekly 12 mg injection is 1.2 mL (two pulls) or split twice-weekly (6 mg = 60 units each).

Retatrutide Reconstitution Guide

Retatrutide ships as a lyophilized powder. The injection uses the vial at its 3 mL maximum fill (10 mg/mL, 10 units per mg); the nasal spray ships pre-mixed and delivers 0.6 mg per spray, so each dose is spread over more sprays.

Injection (vial)

BAC	Conc.	12 mg
3 mL	10 mg/mL	1.2 mL · 2 draws
2 mL	15 mg/mL	0.8 mL · 80 u
10 mg vial · 1 mL	10 mg/mL	1.0 mL = whole vial (10 mg max)

Vial holds up to ~3 mL. 2 mL fits 12 mg in one syringe but gives non-round units. U-100. The 10 mg vial with 1 mL BAC lands on the same 10 mg/mL, so the unit ladder above is unchanged; it covers phases 1–3 (one vial ≈ five 2 mg doses) and is the lower-cost entry point before the 30 mg vial.

Pen Vial — 3 mL

Format	Conc.	1 mg
3 mL (as supplied)	10 mg/mL	0.1 mL · 10 u

Ships pre-reconstituted; no BAC water is added. 100 mcg per unit on a U-100 scale.

Reconstitution steps

Inspect the vial. Confirm label and intact powder.
Wipe the stoppers. Alcohol swab on both vials.
Draw BAC water. 3 mL into the vial for injection (10 mg/mL).
Inject down the wall. Release water slowly down the inside wall, not onto the powder.
Swirl, do not shake. Roll gently until clear.
Refrigerate. Store at 2–8 °C; do not freeze.

How to use the pen vial

Inspect the vial. Confirm the label and strength. The solution should be clear and colorless.
Never add water. A pen vial ships at its final 3 mL volume. Adding bacteriostatic water would dilute it and invalidate every unit figure on this page.
Load the vial into the pen. Unscrew the pen's cartridge holder, seat the vial, and screw the holder back on until firm.
Attach a fresh needle tip. Screw a new disposable pen needle onto the holder, then pull off the outer and inner caps. Use a new tip for every dose.
Prime the pen. Dial 2 units, hold the pen needle-up, tap the holder so any air rises to the top, and press the button until a drop appears at the tip. Repeat until it does.
Spin to the dose. Turn the dial to the unit figure from the table above. If you overshoot, spin back — never press the button to correct an overshoot.
Re-check the dial at each titration step. The ladder changes the unit figure roughly every four weeks — confirm the current step before dialing rather than repeating last month's number.
Inject and hold. Press the button all the way down, then keep the needle in place for about ten seconds before withdrawing so the full dose is delivered.
Remove and dispose of the needle. Unscrew the tip into a sharps container. Never store the pen with a needle attached — it lets solution leak out and air in.
Cap and refrigerate. Store the pen with the vial still seated at 2–8 °C. Do not freeze.

How to use the nasal spray

Prime first use. Pump 2–3 sprays into a tissue until a fine, even mist appears.
Position. Tilt the head slightly forward; insert the tip just inside one nostril, aimed slightly outward toward the ear — not at the septum.
Spray and breathe. Press once while breathing in gently; do not sniff hard, which sends the solution down the throat instead of onto the mucosa.
Alternate nostrils. For multi-spray doses, switch nostrils each spray to spread absorption and limit irritation.
Count per the protocol. Use the sprays-per-dose shown above; if a dose isn't a whole number, round up.
Between uses. Wipe the tip, recap, and refrigerate.

See the bacteriostatic water guide for diluent handling, or the reconstitution calculator to work any other volume.

How Retatrutide Works

Retatrutide simultaneously activates three incretin/metabolic receptors. GLP-1 and GIP agonism reduce appetite and improve glucose handling, while glucagon-receptor agonism is thought to increase energy expenditure and support fat metabolism. This triple action is the basis for the large weight-reduction effects reported in trials, and the glucagon component differentiates it from GLP-1 and dual GLP-1/GIP agonists.

GLP-1

Appetite reduction and improved glucose-dependent insulin response.

GIP

Complementary incretin effect on glucose and appetite.

Glucagon

Thought to raise energy expenditure and support lipolysis.

Open question

Long-term outcomes and approval status are still being established in Phase 3.

Who Should Avoid Retatrutide

MTC / MEN2 history

Like other incretin agents, a personal/family history of medullary thyroid carcinoma or MEN2 is a key caution.

Pancreatitis history

Incretin agonists carry a pancreatitis caution.

Pregnancy & lactation

Not appropriate; no safety data in this context.

Severe GI disease

Gastroparesis or significant GI disease may be worsened.

Retatrutide Side Effects & Safety

Gastrointestinal

Nausea, vomiting, diarrhea, and constipation are the most common, dose-dependent, and the reason for slow titration.

Heart rate

Modest increases in heart rate have been observed with incretin agents.

Glucose / appetite

Reduced appetite and improved glucose handling; watch for hypoglycemia if combined with other agents.

Titration matters

Escalating too fast worsens GI effects; splitting to twice weekly can smooth them.

Timeline & What to Monitor

Timeframe	Commonly tracked	Notes
Weeks 1–4	GI tolerability at the starting step	Hold or slow escalation if GI effects are strong.
Each step (~4 wks)	Tolerability before escalating	Only advance the ladder when the current step is tolerated.
Ongoing	Weight, glucose, heart rate	Track the metabolic endpoints and vitals.

Clinical Evidence Context

Phase 2

A Phase 2 obesity trial reported large dose-dependent weight reductions (Jastreboff et al., NEJM, 2023).

Phase 3 (TRIUMPH)

The Phase 3 program is evaluating efficacy and safety at scale.

Mechanistic novelty

The glucagon component distinguishes it from GLP-1 and GLP-1/GIP agents.

Boundary

Not yet approved; research/investigational context only.

Storage & Handling

State	Storage	Notes
Lyophilized (powder)	−20 °C long-term; fridge short-term	More stable than reconstituted solution.
Reconstituted (liquid)	2–8 °C	Use within ~3–4 weeks; do not freeze.
Appearance	Clear, colorless	Discard cloudy or particulate solutions.

Mistakes & Troubleshooting

Strong nausea. Hold the current step or split to twice weekly; don't escalate until tolerated.
Escalating too fast. Stay ~4 weeks per step; GI effects track the speed of titration.
Exact dosing. Spray increments are 0.6 mg and round up, so a spray dose can slightly exceed the target; use the injection for precise amounts.
Left out overnight. Treat reconstituted solution as compromised and discard.

Retatrutide vs Other Incretin Agents

Feature	Retatrutide	Semaglutide / Tirzepatide
Targets	GLP-1 + GIP + glucagon (triple)	GLP-1 (semaglutide) / GLP-1+GIP (tirzepatide)
Cadence	Weekly, titrated	Weekly, titrated

Blood Tests & Monitoring

Marker	Why	Timing
Fasting glucose / HbA1c	Metabolic effect and hypoglycemia risk with other agents	Baseline + periodic
CMP / lipase	General safety; pancreatitis caution	Baseline / as advised
Heart rate / BP	Incretin agents can modestly raise heart rate	Periodic

Frequently Asked Questions

What is Retatrutide?

An investigational triple agonist (GLP-1/GIP/glucagon) studied for weight and metabolic outcomes. It is dosed weekly with titration and is investigational.

Once-weekly or twice-weekly?

Both, at the same weekly total. The ladder is 2 → 4 → 8 → 12 mg/week (~4 weeks per step). Once-weekly gives the full dose in one injection; twice-weekly splits it in half, which can smooth GI side effects.

How is the injection dosed vs the nasal spray?

Separate protocols. At 10 mg/mL, injection is 10 units per mg (12 mg = 120 u — split into two draws, or run twice-weekly at 6 mg = 60 u). The spray uses a 5 mL fill → 0.6 mg per spray, so the weekly dose is 4–20 sprays (2–10 if split twice-weekly), rounded up to whole sprays.

How is Retatrutide reconstituted?

Injection uses 30 mg in 3 mL BAC water (the vial's max fill) → 10 mg/mL, 10 units per mg. The nasal spray ships pre-mixed and delivers 0.6 mg per spray.

What is the pen-vial format?

A 30 mg pen vial supplied already reconstituted to 3 mL. That is the same fill the injection protocol above assumes (10 mg/mL, 1 mg = 10 units), so the titration ladder in units is unchanged; the pen just arrives pre-mixed.

Is this page medical advice?

No. It is an educational research reference and does not diagnose, treat, or prescribe. Consult a licensed clinician before considering any compound.

Retatrutide Formats & Sourcing

The protocols above are written against the formats Retatrutide is actually supplied in. Batch-specific Certificates of Analysis are issued per lot; always verify the strength on the label against the figures used here before calculating anything.

Format	Supplied as
Vial — 10 mg	10 mg lyophilized powder
Vial — 30 mg	30 mg lyophilized powder
Pen vial	Pre-reconstituted, 3 mL
Nasal spray	Pre-mixed, 0.6 mg per spray
Nasal spray — 5-pack	Bulk: five nasal spray units
Vial — 5-pack	Bulk: five vial units

5-packs are available for the nasal spray and vial formats. Strengths and formats are listed as sold; confirm against the product page and the batch COA.

Reference material for this protocol, with batch COA:

View Retatrutide on Spyro Peptides →

Purity 99+% HPLC Batch COA available Research use only

References

Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity (Phase 2). N Engl J Med (2023).
Rosenstock J, et al. Retatrutide in type 2 diabetes (Phase 2). Lancet (2023).
Eli Lilly. TRIUMPH Phase 3 retatrutide program (clinical trial registrations).
Coskun T, et al. Pharmacology of the triple agonist retatrutide. Cell Metab / Mol Metab (2022).