Retatrutide Dosing Guide — 2mg to 12mg Titration Protocol

What Dose Should You Start At?

Retatrutide (LY3437943) is a triple hormone receptor agonist that activates GLP-1, GIP, and glucagon receptors simultaneously. Due to the glucagon receptor component — which is not present in tirzepatide ("tirz") or semaglutide — all dosing protocols start at the lowest tier regardless of prior GLP-1 experience.

The starting dose is 2mg/week for the first 4 weeks. This applies even if you are switching from tirzepatide at 15mg/week. The glucagon receptor activation introduces pharmacological effects your body has not been exposed to, and starting higher significantly increases the risk of severe nausea, vomiting, and GI distress.

Standard Titration Schedule (Clinical Trial Protocol)

This schedule is based on the dosing arms used in retatrutide Phase 2 and Phase 3 clinical trials. Each tier lasts a minimum of 4 weeks:

Community Titration Approaches

The clinical trial protocol increases dose every 4 weeks. In practice, many providers and experienced users take a different approach:

Slower Titration (5-6 Weeks Per Tier)

Staying longer at each dose — particularly at 4mg and 6mg — reduces the intensity of GI side effects. The body adapts to each dose level more completely before adding more receptor stimulation. There is no clinical penalty for titrating slowly. Your body reaches the same steady-state levels — just with fewer days of intense nausea.

The 6mg to 8mg Wall

Community reports consistently flag the jump from 6mg to 8mg as the hardest transition. This is where glucagon receptor effects intensify most noticeably — nausea, reduced appetite (sometimes to the point of difficulty eating enough), and increased body heat. Strategies for this transition:

• Split the 8mg dose into two 4mg injections (see split dosing section below)
• Stay at 6mg for 6-8 weeks instead of 4
• Increase to 7mg first (possible with compounded vials) before jumping to 8mg

Lower Maintenance Doses

Some users find their optimal dose is 6mg or 8mg and stay there long-term rather than pushing to 12mg. If you're losing 1-2 lbs/week consistently at 8mg, increasing to 12mg adds more side effects without proportionally more weight loss. Find your effective dose and stay there.

Split Dosing and Microdosing Protocols

Split dosing means dividing your weekly dose into smaller, more frequent injections. Instead of 8mg once per week, you'd inject 4mg twice per week (e.g., Monday and Thursday). This approach is increasingly popular with retatrutide because the glucagon receptor activation produces a sharper nausea spike at peak blood levels than tirzepatide.

Why Split Dosing Works

• Lower peak blood levels = less nausea in the 24-48 hours after injection
• Higher trough levels = more consistent appetite suppression throughout the week
• Retatrutide's half-life is ~6 days (144 hours), which means once-weekly dosing produces significant peaks and troughs

Common Split-Dose Protocols

How to Calculate Split Doses

1. Determine your total weekly dose (e.g., 8mg)
2. Divide by number of injections (8mg / 2 = 4mg per injection)
3. Use the GLP-1 dose calculator to convert mg to units for your specific vial concentration
4. Or use the split-dose calculator which does all of this automatically

Track every retatrutide dose, weight trend, and side effect in one app

• Log reta doses with pharmacokinetic blood level modeling
• Track weight moving averages and body composition
• Monitor side effects at each titration tier

Get Regimen Free

How to Calculate Your Dose

The formula for all reconstituted peptides:

Or skip the math: GLP-1 Dose Calculator

For split dosing, just divide: 4mg split into two injections = 2mg each = 33 units per injection.

Dose Charts by Vial Size

5mg Vial + 1mL BAC Water (5.0 mg/mL)

Best for: First 4-8 weeks of titration (2-4mg doses)

12mg Vial + 2mL BAC Water (6.0 mg/mL)

Best for: Titration through 2-6mg range

30mg Vial + 2mL BAC Water (15.0 mg/mL)

Best for: Maintenance dosing at 6mg+ (finishes within 28-day stability window)

For detailed reconstitution instructions, see our complete Retatrutide Reconstitution Calculator Guide.

Half-Life and Injection Timing

Retatrutide has a half-life of approximately 6 days (144 hours). Key implications:

• Steady state is reached within 4-5 weeks at any given dose
• Once-weekly dosing is supported by the half-life, but produces noticeable peaks and troughs
• Best injection day/time: Most users inject in the evening so that peak nausea (usually 12-36 hours post-injection) occurs during sleep and the following day, with recovery by the second evening
• Consistency matters: Inject on the same day(s) each week at approximately the same time

Use our half-life visualizer to see how retatrutide blood levels change throughout the week at different dose frequencies.

When to Increase Your Dose

Increase your dose only when ALL of these are true:

1. You've been at the current dose for at least 4 weeks (preferably 5-6)
2. Weight loss has stalled for 2+ weeks (less than 0.5 lbs/week)
3. You're tolerating the current dose well (nausea is minimal or gone)
4. You're eating adequate protein (1.2-1.6g/kg/day) and not over-restricting calories
5. You're not experiencing significant side effects that would worsen with a higher dose

When NOT to Increase Your Dose

Do NOT increase if:

• You're still losing weight consistently at the current dose (even if it's "only" 1 lb/week — that's 52 lbs/year)
• You're experiencing persistent nausea, vomiting, or GI issues
• Your resting heart rate has increased more than 15 bpm from baseline
• You haven't been at the current dose for at least 4 full weeks
• You're not eating enough (undereating + dose increase = muscle loss and metabolic adaptation)

Tracking Your Dosing Protocol

What to track at each dose tier:

• Dose amount and timing (especially if split dosing)
• Weight (daily or every other day for accurate moving averages)
• Side effects with severity ratings (nausea, appetite, energy, GI)
• Resting heart rate (check weekly — retatrutide can increase it 5-12 bpm)
• Protein intake (aim for 1.2-1.6g/kg — track in any food app and log in Regimen)
• Body measurements and progress photos (weight alone doesn't capture body composition changes)

The Regimen app tracks retatrutide alongside all your other compounds with pharmacokinetic blood level modeling, so you can see exactly where your levels are throughout the week — especially useful if you're split dosing.

Frequently Asked Questions