Retatrutide Dosing Protocol
Retatrutide (LY3437943) is an investigational triple receptor agonist targeting GIP, GLP-1, and glucagon receptors simultaneously. Phase 2 trials demonstrated unprecedented weight loss of up to 24% at the highest dose, making it the most potent obesity treatment studied to date.
Key Points
Step-by-Step Guide
Understand Trial Dosing
Phase 2 trial doses: 1, 4, 8, and 12 mg weekly. All arms used a titration approach starting at lower doses and escalating monthly.
Titration Approach
Start at 1 mg weekly for 4 weeks, then escalate in 2-4 mg increments every 4 weeks to the target dose. This mirrors the trial methodology for GI tolerance.
Administration
Once-weekly subcutaneous injection, similar to semaglutide and tirzepatide. Rotate injection sites between abdomen, thigh, and upper arm.
Note Triple Mechanism
The glucagon receptor component adds thermogenic and hepatic fat-reducing effects not present in dual agonists. This may cause unique metabolic effects requiring monitoring.
Await Phase 3 Data
As an investigational compound, optimal dosing will be established by Phase 3 trials. Current dosing information is preliminary and subject to revision.
Warnings & Precautions
- !Retatrutide is investigational—NOT approved for any use.
- !Phase 3 trials are ongoing; safety profile is incomplete.
- !Glucagon receptor agonism may cause blood sugar spikes in diabetics.
- !GI side effects expected similar to or greater than other incretin therapies.
Frequently Asked Questions
How does retatrutide compare to tirzepatide?
Retatrutide adds glucagon receptor agonism to the GIP/GLP-1 dual agonism of tirzepatide. Phase 2 data suggests greater weight loss (24% vs 22%) but with potentially more side effects. Direct comparison awaits Phase 3 data.
When will retatrutide be available?
Phase 3 trials are underway. If successful, FDA submission could occur by 2025-2026, with potential approval 1-2 years later. Timeline is subject to trial outcomes.
What makes the glucagon component unique?
Glucagon receptor activation increases energy expenditure and hepatic fat oxidation. This thermogenic effect may produce weight loss from increased caloric burn, complementing the appetite suppression from GIP/GLP-1 agonism.