Overview

Retatrutide, an investigational molecule by Eli Lilly and Company, is emerging as a promising therapeutic agent in the field of obesity management. Revealed in phase 2 trials, retatrutide has demonstrated significant efficacy in weight reduction among participants with obesity or overweight, achieving a mean weight loss of up to 17.5% over 24 weeks and 24.2% over 48 weeks. These results were highlighted at the American Diabetes Association's 83rd Scientific Sessions and published in The New England Journal of Medicine.

Distinctive in its mechanism, retatrutide combines glucagon receptor agonism with GIP and GLP-1 receptor agonism. This novel approach may account for the notable weight reduction observed in trials, surpassing many current treatments. The TRIUMPH phase 3 development program is further exploring retatrutide's efficacy in chronic weight management and associated conditions like obstructive sleep apnea (OSA) and knee osteoarthritis (OA) in individuals with obesity and overweight.

In comparison to Semaglutide and Tirzepatide, retatrutide's unique inclusion of glucagon receptor agonism alongside GIP and GLP-1 receptor agonism offers a distinct pharmacological profile. While Semaglutide is a GLP-1 receptor agonist and Tirzepatide combines GLP-1 and GIP receptor agonism, retatrutide's triple mechanism could potentially provide broader metabolic benefits. The phase 2 study, involving various doses and dose-escalation regimens, underscores retatrutide's safety profile, similar to other incretin-based therapies, with gastrointestinal side effects being the most common adverse events.

The ongoing research and trials will determine retatrutide's place in treating obesity and its complications, potentially broadening the spectrum of effective pharmacotherapeutic options for this chronic disease.

Dosage

The FDA-recommended dosing schedule for Retatrutide does not yet exist, but trials have focused, particularly for weight loss, on different dosage than prior GLP-1 agonist-type drugs that involve a gradual increase in dosage over several weeks. This schedule is designed to help the body adjust to the medication while minimizing side effects. The initial dose escalation schedule starts at a low dose and increases incrementally over a period of 48 weeks. The maintenance dose is then established from week 48 onwards.

Presuming 5MG bottles of raw Retatrutide mixed with 2ML of bacteriostatic water and using a standard standard U-100 insulin syringe, an entire course of Retatrutide can be completed with 39 bottles of the peptide.

To calculate the dosage schedule for Retatrutide using a 5 mg vial reconstituted with 2 mL of bacteriostatic water, we first need to establish the concentration of the solution. Then we can determine the weekly dosage based on the phase 2 study data and calculate the number of vials required.

1. Concentration Calculation:

- 5 mg of Retatrutide is reconstituted in 2 mL of water, resulting in a concentration of 2.5 mg/mL.

- Convert this to mcg/mL: 2.5 mg/mL = 2500 mcg/mL.

2. Weekly Dosage in mcg (for a 4 mg Dose):

- Convert 4 mg to mcg: 4 mg = 4000 mcg.

3. Volume Calculation for 4000 mcg:

- Volume in mL for a 4000 mcg dose: \( \frac{4000 \text{ mcg}}{2500 \text{ mcg/mL}} = 1.6 \text{ mL} \).

4. Syringe Measurement:

- If using a 0.5 mL syringe marked in 50 units, where 1 unit equals 0.01 mL (since 0.5 mL = 50 units),

- For 1.6 mL: \( 1.6 \text{ mL} \times 100 \text{ units/mL} = 160 \text{ units} \).

Therefore, for a weekly dose of 4 mg of Retatrutide, you would draw up 160 units on a 0.5 mL, 50-unit insulin syringe. This calculation assumes that you are administering the entire dose in one injection. If the syringe's maximum capacity is less than the required volume, the dose may need to be split into multiple injections.

As a reminder, these calculations are for informational purposes, and actual medication dosing should always be performed under the guidance of a healthcare professional.