GLP-1 / Weight Loss

Retatrutide

Half-life: 6d Subcutaneous injection (abdomen, thigh, or upper arm); rotate sites. Once weekly.

Warnings. Investigational only - not approved anywhere. Dose-dependent GI side effects and transient heart rate increase observed in trials.

Mechanism

Triple receptor agonist (GIP/GLP-1/glucagon); combines appetite suppression and improved insulin sensitivity with glucagon-mediated increases in energy expenditure and hepatic fat oxidation.

Overview

Retatrutide is an investigational triple agonist targeting GIP, GLP-1, and glucagon receptors. Phase 2 trials showed unprecedented weight loss of up to roughly 24% of body weight at 48 weeks. It remains in clinical development and is not yet FDA-approved.

Protocols

Trial-Style Titration

Official ADVANCED

Escalation schedule mirroring phase 2 trial design, from 2mg to 12mg weekly.

Goal: Weight loss

Step 1 4w

2 mg · 1×/day

2mg once weekly - initiation dose.

Step 2 4w

4 mg · 1×/day

4mg once weekly.

Step 3 4w

6 mg · 1×/day

6mg once weekly.

Step 4 4w

8 mg · 1×/day

8mg once weekly.

Step 5 4w

12 mg · 1×/day

12mg once weekly - highest studied dose. Many protocols cap at 8mg if well tolerated.