Retatrutide Dosage Calculator

Retatrutide (development code LY3437943) is a first-in-class triple incretin receptor agonist developed by Eli Lilly that simultaneously targets the glucagon-like peptide-1 (GLP-1) receptor, the glucose-dependent insulinotropic polypeptide (GIP) receptor, and the glucagon (GCG) receptor. This triple mechanism of action distinguishes it from all currently approved incretins, which target either one (GLP-1 monotherapy) or two (GLP-1/GIP dual agonism) of these receptors. By adding glucagon receptor co-agonism to the established dual incretin framework, retatrutide may produce additional thermogenic and energy expenditure-enhancing effects beyond those achievable with dual agonists.

In the Phase 2 TRIUMPH trial published in the New England Journal of Medicine in 2023, retatrutide at the highest dose studied (12 mg per week) produced a mean body weight reduction of 24.2% over 48 weeks in adults with obesity — exceeding any weight loss previously observed in a non-surgical obesity drug trial at that duration and marking a potential inflection point in pharmacological weight management research. The compound is currently advancing through Phase 3 clinical development.

Retatrutide's triple receptor co-agonism harnesses three complementary metabolic pathways. GLP-1 receptor activation drives glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying, and signals satiety through central nervous system pathways — the same mechanism exploited by semaglutide. GIP receptor activation enhances insulin secretion and may improve tolerability by counteracting GLP-1-induced nausea via opposing signaling in the area postrema.

The addition of glucagon receptor agonism is the novel component of the retatrutide profile. Glucagon receptor activation in the liver promotes hepatic glucose output (normally undesirable) but at the doses used in incretin-based therapies is thought to be outweighed by GLP-1/GIP-mediated insulin effects, and instead contributes to increased energy expenditure, enhanced fat oxidation, and reduced hepatic fat accumulation. Preclinical data suggest that glucagon receptor agonism raises metabolic rate through thermogenic pathways in brown adipose tissue, which may partly explain the superior weight loss magnitude observed with retatrutide versus dual agonists.

Retatrutide lyophilized powder is reconstituted using bacteriostatic water for injection. Using a sterile syringe and needle, draw the target volume of bacteriostatic water and inject it slowly down the side wall of the retatrutide vial. Allow the solution to sit undisturbed for 60–90 seconds, then gently swirl (never shake) until the powder fully dissolves. The reconstituted solution should be clear to very slightly pale yellow and free of particulates.

For a 5 mg vial with 1 mL of bacteriostatic water, the concentration is 5,000 mcg/mL. A 2 mg dose (2,000 mcg) requires 0.40 mL (40 IU on a U100 syringe). For a 10 mg vial with 1 mL, the concentration doubles to 10,000 mcg/mL. Administer subcutaneously with a 27–31 gauge insulin syringe, rotating injection sites at each dose.

The Phase 2 TRIUMPH trial used six weekly dose escalation tiers to characterize retatrutide's dose-response profile: 1 mg, 4 mg, and 12 mg per week in the primary dose-ranging arms, with a 2 mg arm included for additional resolution. A titration schedule was employed: doses were typically started at 1 mg per week and stepped up every four weeks until reaching the assigned target maintenance dose.

The 12 mg per week dose, which produced the 24.2% mean weight reduction over 48 weeks, required a titration sequence of approximately 1 mg (weeks 1–4), 2 mg (weeks 5–8), 4 mg (weeks 9–12), 8 mg (weeks 13–16), and 12 mg (week 17 onward). The 4 mg maintenance arm reached a mean weight reduction of approximately 16.9% at 48 weeks, suggesting a meaningful dose-response relationship across the studied range.

Using the calculator: a 10 mg vial reconstituted with 1 mL of bacteriostatic water gives 10,000 mcg/mL. The 12 mg maintenance dose (12,000 mcg) would require 1.2 mL — slightly more than one vial, so researchers at maximum doses typically use two vials and split appropriately.

Store lyophilized retatrutide at 2–8°C in the refrigerator, protected from direct light. Do not freeze. After reconstitution with bacteriostatic water, the solution should be stored at 2–8°C and used within 28 days. At room temperature (15–25°C), reconstituted peptide solutions degrade more rapidly; if a vial needs to be used within a day or two after brief room-temperature storage, it should be acceptable, but do not leave reconstituted retatrutide at ambient temperature for extended periods. Label each vial with the reconstitution date and discard after 28 days regardless of remaining volume.

In the TRIUMPH Phase 2 trial, the most common adverse events were gastrointestinal: nausea (incidence up to 56% at 12 mg), diarrhea, vomiting, decreased appetite, and constipation — consistent with the class effects of incretin-based therapies and most severe during dose escalation. Injection-site reactions occurred in a small percentage of participants. Reductions in bone mineral density, which may be related to glucagon receptor agonism, were noted at higher doses and warrant further study. As with other incretin therapies, theoretical thyroid C-cell concerns from rodent data prompt caution in those with personal or family history of medullary thyroid carcinoma. This is a research chemical for laboratory use only.