Retatrutide

Structure: Triple-acting peptide agonist at GIP, GLP-1, and Glucagon receptors. The glucagon receptor activation is unique — increases energy expenditure and hepatic fat oxidation on top of the appetite suppression from GIP/GLP-1.

Dosage:

• Clinical trial dosing: 1mg/week → 2mg/week → 4mg/week → 8mg/week → 12mg/week (titrated monthly)
• Bodybuilding use: Limited data — most users start at 1-2mg/week and titrate based on response

Administration:

• SubQ injection once weekly
• Titrate slowly over weeks/months

Key Notes:

• Phase 3 clinical trials ongoing — not yet FDA-approved (as of 2025)
• Clinical trials showed up to 24% body weight loss at 48 weeks (most potent of any GLP-1 class drug)
• Glucagon receptor activation differentiates it: increases energy expenditure, promotes hepatic fat oxidation
• Triple mechanism may reduce liver fat (NAFLD/NASH) more effectively than dual agonists
• GI side effects expected to be similar to other GLP-1 agonists
• Resting energy expenditure increase from glucagon component is unique and potentially muscle-sparing
• Very limited real-world bodybuilding data — early adopters only
• Monitor: fasting glucose, HbA1c, lipid panel, liver enzymes, amylase/lipase, heart rate