Retatrutide Dosage Guide: Titration Schedule (2026)

Every patient begins at 2 mg once weekly, regardless of target maintenance dose. This is non-negotiable based on the clinical trial data.

In the Phase 2 trial, one group was assigned to start directly at 4 mg. Their rate of gastrointestinal side effects nearly doubled compared to the group that started at 2 mg and escalated (Jastreboff et al., NEJM 2023). Nausea, diarrhea, and vomiting were all significantly higher in the direct-start group.

The 2 mg starting dose allows the GI tract to adapt to GLP-1 receptor activation. Most side effects that do occur at this dose are mild: slight nausea in the first few days, reduced appetite, and occasionally loose stools. These typically resolve within the first week.

At week 5, the dose doubles to 4 mg once weekly. Appetite suppression becomes noticeably stronger at this level. Most users report a significant reduction in food cravings and portion sizes.

Weight loss accelerates during this phase. In the Phase 2 trial, the 4 mg group had already lost 12.9% of body weight by week 24, compared to 1.6% for placebo.

GI symptoms may briefly return when the dose increases. If nausea is severe, hold at 4 mg for an additional 2-4 weeks before escalating. The clinical trial protocol allowed for dose delays when side effects were intolerable.

The 8 mg dose is where the glucagon receptor activation becomes more pronounced. Energy expenditure increases measurably. The 8 mg group in the Phase 2 trial achieved 22.8% body weight loss at 48 weeks.

For some patients, 8 mg is the optimal maintenance dose. If side effects are manageable and weight loss is progressing well, there is no strict requirement to escalate to 12 mg. The difference between 8 mg and 12 mg at 48 weeks was 1.4 percentage points (22.8% vs 24.2%).

The 12 mg dose produced the highest weight loss in every trial: 24.2% at 48 weeks (Phase 2) and 28.7% at 68 weeks (Phase 3 TRIUMPH-4). This is the maximum studied dose.

At 12 mg, response rates were remarkable. In the Phase 2 trial at 48 weeks (NEJM 2023):

Every single participant on 12 mg lost at least 5% of their body weight. No other obesity medication has achieved a 100% response rate at this threshold.

Continue the 12 mg maintenance dose for as long as treatment is needed. The Phase 3 TRIUMPH-4 trial ran for 68 weeks with continued weight loss throughout, suggesting the plateau has not yet been reached at this timepoint (Lilly TRIUMPH-4 Press Release).

Some practitioners use a more gradual escalation with 2 mg increments every four weeks. This approach reduces GI side effects further and is useful for patients with a history of GLP-1 intolerance.

This schedule takes 20 weeks to reach the maximum dose instead of 12. The tradeoff: slower initial weight loss in exchange for better tolerability. For patients who struggled with nausea on tirzepatide or semaglutide, the slower schedule is often the better choice.

The Phase 2 trial randomized 338 adults with obesity (BMI ≥30) or overweight with at least one weight-related condition to retatrutide or placebo for 48 weeks (Jastreboff et al., NEJM 2023).

Weight loss at 24 weeks (primary endpoint):

Weight loss at 48 weeks (secondary endpoint):

The weight loss curves had not plateaued at 48 weeks. The 8 mg and 12 mg groups were still losing weight when the study ended, suggesting longer treatment durations would produce even greater reductions.

The TRIUMPH-4 trial enrolled adults with obesity and knee osteoarthritis. Results announced in December 2025 confirmed the Phase 2 findings at a longer timepoint (Lilly Press Release, Dec 2025):

The 28.7% weight loss at 68 weeks exceeds both semaglutide (~15% in STEP trials) and tirzepatide (~22.5% in SURMOUNT trials) at similar timepoints.

Seven additional Phase 3 TRIUMPH trials are expected to report results throughout 2026, covering obesity, type 2 diabetes, sleep apnea, chronic low back pain, and metabolic liver disease (ClinicalTrials.gov).

How does retatrutide compare to the current standard of care? The data comes from separate trials with different populations, so direct comparison has limitations. Still, the magnitude of difference is striking.

The glucagon receptor component accounts for much of the difference. Glucagon stimulates hepatic fat oxidation and thermogenesis, burning calories that GLP-1 alone cannot access. This is why retatrutide produces greater weight loss even at a lower milligram dose than tirzepatide.

For a broader comparison of weight loss peptides, see our best peptides for weight loss guide.

Three subcutaneous injection sites are standard:

• Abdomen: The most common site. Pinch a fold of skin at least 2 inches from the navel. Inject at a 45-degree angle.
• Front of thigh: Middle third of the upper leg. Good alternative if the abdomen is sore from repeated injections.
• Back of upper arm: Harder to self-inject but viable with practice.

Rotate injection sites each week. Do not inject into the same spot two weeks in a row. Rotation prevents lipodystrophy (localized fat changes) and reduces injection site irritation.

Inject once per week on the same day each week. The specific day does not matter. Choose a day that is easy to remember: many users pick Sunday or Monday.

The time of day is also flexible. Morning or evening, with or without food. Consistency matters more than timing. If you miss your scheduled day, inject as soon as you remember within 3 days. If more than 3 days have passed, skip the missed dose and resume on the next scheduled day.

Retatrutide has a half-life of approximately 6 days, which supports the once-weekly dosing schedule. Steady-state blood levels are typically reached by week 4-5 of treatment.

Use bacteriostatic water, not sterile water. The benzyl alcohol preservative allows the reconstituted solution to last 28-30 days refrigerated. Sterile water has no preservative and must be used within 5-7 days. See our peptide storage guide for detailed storage instructions.

1. 1.Clean the top of the retatrutide vial and the BAC water vial with alcohol swabs.
2. 2.Draw your chosen volume of BAC water into the syringe. For a 10 mg vial, 2 mL of BAC water gives a concentration of 5 mg/mL (convenient for dosing).
3. 3.Insert the needle into the retatrutide vial at an angle. Let the water run slowly down the inside wall of the vial. Do not spray directly onto the powder.
4. 4.Swirl gently. Never shake. Shaking creates foam and can damage the peptide.
5. 5.Wait until the powder is fully dissolved. The solution should be clear and colorless. If cloudy, let it sit in the fridge for 15-30 minutes and swirl again.
6. 6.Label the vial with the date and concentration.
7. 7.Refrigerate immediately.

Use our reconstitution calculator to determine exact volumes for your vial size and target dose. For general reconstitution guidance, see how to reconstitute peptides.

With a 10 mg vial reconstituted in 2 mL BAC water (5 mg/mL concentration):

For the 8 mg and 12 mg doses, a higher concentration is more practical. Reconstituting a 10 mg vial in 1 mL BAC water gives 10 mg/mL:

Store the reconstituted vial in the refrigerator at 2-8°C and use within 30 days.

Most GI side effects occur during the first 1-2 weeks of each dose escalation and resolve without intervention. The severity was described as "mostly mild to moderate" in the NEJM publication, with events partially mitigated by the lower starting dose protocol (Jastreboff et al., NEJM 2023).

The Phase 2 trial included a direct comparison: one 4 mg group started at 2 mg and escalated, while another started directly at 4 mg. The direct-start group experienced nearly double the rate of GI adverse events.

This finding changed the protocol for all subsequent trials. Every Phase 3 TRIUMPH trial uses the 2 mg starting dose. Skipping the initial titration is the single most common mistake in retatrutide dosing, and it is entirely avoidable.

If you have used GLP-1 agonists before and tolerated them well, you still start at 2 mg. Prior GLP-1 experience does not eliminate the need for titration with retatrutide, because the glucagon receptor component introduces a new variable.

Practical strategies that reduce GI symptoms during dose escalation:

• Eat smaller meals. Large meals overwhelm a slowed gastric emptying system. Five small meals outperforms three large ones during titration.
• Avoid fatty foods. Fat takes the longest to digest and is most likely to trigger nausea when gastric emptying is delayed.
• Stay hydrated. Diarrhea and vomiting deplete fluids. Aim for 2-3 liters of water daily.
• Time the injection after your last meal. Injecting before bed, after dinner, means any nausea peaks during sleep.
• Delay escalation if needed. If side effects at 4 mg are intolerable, stay at 4 mg for 6-8 weeks instead of 4. The clinical protocol allowed dose delays.
• Ginger or peppermint tea. Anecdotally helpful for mild nausea. No clinical data, but no risk.