What is the optimal micro‑dosing protocol for retatrutide?

Retatrutide Micro-Dosing Protocol

Critical Context: No Established Micro-Dosing Protocol Exists

There is no published evidence, guideline, or FDA-approved protocol for "micro-dosing" retatrutide—all clinical trial data used standard escalation protocols starting at 1-2 mg weekly, not micro-doses. The available evidence only supports conventional dosing strategies tested in phase 2 trials.

Evidence-Based Starting and Escalation Protocol

Based on the highest quality phase 2 trial data, the optimal retatrutide protocol is:

Standard Dosing Strategy (Not Micro-Dosing)

• Start at 2 mg subcutaneously once weekly 1, 2
• Escalate by doubling the dose every 4 weeks to reach target maintenance doses of 4 mg, 8 mg, or 12 mg weekly 1, 2
• The 2 mg starting dose (rather than 4 mg) significantly reduces gastrointestinal adverse events while maintaining efficacy 1, 2

Dose-Response Data from Phase 2 Trials

Weight loss at 48 weeks:

• 1 mg weekly: -8.7% body weight 2
• 4 mg weekly (2 mg start): -17.1% body weight 2
• 8 mg weekly (2 mg start): -22.8% body weight 2
• 12 mg weekly (2 mg start): -24.2% body weight 2

For type 2 diabetes, HbA1c reduction at 24 weeks:

• 4 mg weekly (2 mg start): -1.39% 1
• 8 mg weekly (2 mg start): -1.99% 1
• 12 mg weekly (2 mg start): -2.02% 1

Why Lower Starting Doses Matter

The 2 mg starting dose versus 4 mg starting dose reduced gastrointestinal side effects (nausea, diarrhea, vomiting) from 50% to 13-35% of participants while achieving equivalent long-term efficacy 1, 2. This dose-dependent tolerability profile is the only evidence supporting gradual escalation.

Safety Monitoring Requirements

• Gastrointestinal adverse events (nausea, diarrhea, vomiting, constipation) occur in 35% of patients and are dose-related but mostly mild-to-moderate 1
• Heart rate increases of up to 6.7 beats/minute peak at 24 weeks then decline; this may offset cardiovascular benefits of weight loss 3, 2
• No severe hypoglycemia or deaths occurred in phase 2 trials 1

Critical Pitfall to Avoid

Do not attempt dosing below 1 mg weekly or use non-standard "micro-dosing" protocols—there is zero clinical evidence for efficacy or safety below the 1 mg dose tested in trials 1, 2. The 1 mg dose itself showed minimal efficacy (-8.7% weight loss at 48 weeks) compared to higher doses 2.

Practical Algorithm

1. Start at 2 mg subcutaneously once weekly for the first 4 weeks 1, 2
2. Increase to 4 mg weekly at week 5 if tolerated 1, 2
3. Increase to 8 mg weekly at week 9 if additional efficacy needed and tolerated 1, 2
4. Increase to 12 mg weekly at week 13 for maximum weight loss if tolerated 1, 2
5. Maintain at the highest tolerated dose for ongoing treatment 1, 2

If gastrointestinal side effects are intolerable, remain at current dose for an additional 4 weeks before attempting escalation 1, 2.