Weekly escalation schedules, reconstitution tables for every vial size, injection timing, nausea management during escalation, and cycle length guidance.
Retatrutide is dosed once weekly via subcutaneous injection. Unlike some peptides where dose selection is relatively fixed, retatrutide uses a mandatory dose escalation schedule — starting low to allow GI tolerance to develop, then stepping up toward a maintenance dose over several weeks. This escalation approach is the same used for tirzepatide and semaglutide, and directly addresses the nausea that causes the most research protocol discontinuations.
In the Phase 2 trial, 16% of participants on the 12mg dose discontinued due to adverse events — primarily GI side effects during escalation. Slower escalation dramatically reduces this. The difference between a well-tolerated protocol and an abandoned one is almost entirely in how fast you increase the dose.
| Weeks | Weekly Dose | Notes |
|---|---|---|
| 1–4 | 1mg | Initial tolerance phase — GI side effects most likely here |
| 5–8 | 2mg | Step up only if tolerating 1mg well |
| 9–12 | 4mg | First plateau assessment at week 12 |
| 13–16 | 6mg | Many protocols stop here for maintenance |
| 17–20 | 8mg | Higher dose if additional response needed |
| 21+ | 8–12mg | Maintenance dose — hold for duration of protocol |
| Weeks | Weekly Dose | Notes |
|---|---|---|
| 1–4 | 2mg | Starting dose — faster escalation, higher GI risk |
| 5–8 | 4mg | |
| 9–12 | 6mg | |
| 13–16 | 8mg | Maintenance for most research protocols |
| 17+ | 8–12mg | Maximum studied dose — higher GI adverse event rate |
If nausea, vomiting, or significant GI discomfort occurs at a given dose, hold at that dose for an additional 2–4 weeks before escalating. Do not push through significant GI symptoms — this is the most common cause of protocol discontinuation and is preventable with patience during escalation.
Retatrutide comes in lyophilized powder vials. Reconstitute with bacteriostatic water. The most common research vial sizes and their concentrations:
| Vial Size | BAC Water | Concentration | Vol per 2mg | Vol per 4mg | Vol per 8mg |
|---|---|---|---|---|---|
| 5mg | 1mL | 5mg/mL | 0.40mL (40u) | 0.80mL (80u) | N/A |
| 10mg | 2mL | 5mg/mL | 0.40mL (40u) | 0.80mL (80u) | 1.60mL (160u) |
| 20mg | 2mL | 10mg/mL | 0.20mL (20u) | 0.40mL (40u) | 0.80mL (80u) |
| 30mg | 3mL | 10mg/mL | 0.20mL (20u) | 0.40mL (40u) | 0.80mL (80u) |
Inject subcutaneously — abdomen, thigh, or upper arm. Rotate injection sites weekly. Reconstituted solution should be refrigerated and used within 28 days. Do not freeze reconstituted solution.
Inject on the same day each week. Retatrutide's ~6-day half-life means consistent weekly timing maintains stable blood levels. Missing a dose by 1–2 days won't cause major disruption; missing 3+ days may cause a small "re-start" GI effect when resuming.
Unlike some GLP-1 compounds, retatrutide can be injected regardless of meal timing — it's not an immediate-release compound that requires fasting. Many researchers inject at night to sleep through the peak GI effects during dose escalation.
GLP-1 class compounds including retatrutide produce both fat and lean mass loss. Research protocols targeting body composition optimization combine retatrutide with high protein intake (1.6–2.2g/kg/day) and resistance training to preferentially preserve muscle during weight loss. This is especially important at higher doses where caloric restriction becomes pronounced.
Retatrutide's Phase 2 ran 48 weeks — and weight loss had not plateaued. Research protocols typically run 24–48 weeks. Weight regain after stopping is a documented phenomenon with GLP-1 class drugs (observed with semaglutide and tirzepatide); the same is expected with retatrutide. This is a biological feature of the mechanism — appetite suppression is removed when the drug is cleared.
| Protocol Type | Duration | Target Dose | Notes |
|---|---|---|---|
| Short cycle | 16–24 weeks | 4–6mg/week | Conservative dose, assess response |
| Standard cycle | 24–36 weeks | 6–8mg/week | Most common research approach |
| Extended cycle | 36–48 weeks | 8–12mg/week | Maximum Phase 2 timeframe |
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