Retatrutide

Retatrutide is the newest and most potent "triple-agonist" currently in clinical research. While Semaglutide (GLP-1) and Tirzepatide (GLP-1/GIP) target one or two pathways, Retatrutide targets three: GLP-1, GIP, and Glucagon (GCGR).

The addition of the Glucagon receptor agonist is a "game changer" in research because it specifically increases energy expenditure (metabolic rate) and targets liver fat more aggressively than its predecessors.
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1. Reconstitution & Dosage
Retatrutide is typically found in 5mg or 10mg lyophilized vials. Because of its extreme potency, precise measurements are mandatory.

• Reconstitution: Add 2ml of Bacteriostatic Water to a 10mg vial.
• The Concentration: This creates 5mg per 1ml.
• Syringe Measurement (U-100 Insulin Syringe):
o 20 units (0.20ml) = 1.0mg
o 40 units (0.40ml) = 2.0mg
o 80 units (0.80ml) = 4.0mg
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2. The Triple-Agonist Protocol (Step-Up)
Retatrutide research emphasizes a very cautious escalation to manage the increased metabolic load and potential heart rate elevation.

Phase Dosage Frequency Duration
Stage 1 (Initiation) 2.0mg Once Weekly Weeks 1–4
Stage 2 (Escalation) 4.0mg Once Weekly Weeks 5–8
Stage 3 (Advanced) 8.0mg Once Weekly Weeks 9–12
Stage 4 (Maximum) 12.0mg Once Weekly Maintenance

Research Strategy: Most protocols suggest staying at the lowest effective dose. If significant weight loss is occurring at 2mg or 4mg, researchers often do not escalate further to minimize stress on the heart and GI tract.
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3. Administration & Timing

• Subcutaneous (SubQ): Standard injection into abdominal fat, thigh, or back of the arm.

• Timing: Once weekly. Due to the Glucagon component, some researchers prefer morning administration as it may slightly increase body temperature and energy levels.

• Site Rotation: Essential. Move the injection site at least one inch away from the previous spot every week.
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4. Unique Potential Side Effects
Because Retatrutide hits three receptors, it has a unique side effect profile compared to Tirzepatide.
• Increased Heart Rate: The Glucagon receptor can cause a more noticeable increase in resting heart rate. Researchers monitor this closely.
• Skin Sensitivity (Allodynia): Some report a "tingling" or sensitive skin sensation, common with high-potency GLP-1s.
• Suppressed Thirst: Like other incretins, it can blunt the thirst mechanism. Dehydration is a major risk.
• Acute Nausea: Often more pronounced during the first 24 hours of a dose increase.
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5. Research Pro-Tips
• The "Glucagon Guard": Because Retatrutide increases metabolic rate, caloric intake must be monitored to ensure it doesn't drop too low, which can lead to severe muscle wasting.
• Liver Health: Retatrutide is specifically being studied for NAFLD (Fatty Liver). It is considered the most "liver-protective" of the weight-loss peptides.
• Storage: Once reconstituted, Retatrutide is very sensitive. It must be refrigerated and used within 30 days.
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Quick Checklist for a 10mg Vial:
• At 2mg/week: One vial lasts 5 weeks.
• At 4mg/week: One vial lasts 2.5 weeks.
• Supplies: 31g Insulin syringes.