Metabolic supportsubcutaneous

Retatrutide

Investigational triple GLP-1 / GIP / glucagon receptor agonist studied for weight management.

Researched for

Metabolic HealthBody CompositionWeight ManagementAppetite Regulation

Not yet audited

We have not published an audit on Retatrutide. Everything below is reference material, not our own reading of the literature, treat it as a starting point for questions, not as a grade.

How it is thought to work

Triple agonism of GLP-1, GIP, and glucagon receptors; studied for appetite regulation and energy expenditure.

Retatrutide is an experimental once-weekly injection that activates three hormone receptors at the same time, ones involved in controlling blood sugar, appetite, and energy use, which may help reduce body weight and improve blood sugar levels.

What sources report

Reference, not a recommendation

These are figures published elsewhere, reproduced with their source. Peppersite does not recommend an amount for Retatrutide or for anything else, and nothing below has been checked against the study it came from.

Amount	Frequency	Route	Reported by
Standard: 1 mg titrating to 12 mg once weekly (Phase 3 TRIUMPH: 1 mg → 2 mg → 4 mg → 6 mg → 9 mg → 12 mg, stepping up every 4 weeks) · Low: 1 mg once weekly · High: 12 mg once weekly	Once per week, on the same day each week48 weeks (Phase 2 reference); 68-72 weeks (Phase 3 TRIUMPH reference) · Every 4 weeks at each dose step; review at 4 mg, 9 mg, 12 mg; slow titration option adds 2-4 weeks per dose step when GI symptoms persist	Subcutaneous injection	Peptide Dosing Protocols What it saysHide (secondary reference; provider confirmation required). Retatrutide is dosed once weekly via subcutaneous injection starting at 1 mg and titrating up every 4 weeks to a maximum of 12 mg following the Phase 3 TRIUMPH schedule.
1-12 mg	Once weekly · Any time of dayTitrate over weeks per response/tolerance	subcutaneous	Reference titration range, provider confirm

Standard: 1 mg titrating to 12 mg once weekly (Phase 3 TRIUMPH: 1 mg → 2 mg → 4 mg → 6 mg → 9 mg → 12 mg, stepping up every 4 weeks) · Low: 1 mg once weekly · High: 12 mg once weekly

Frequency: Once per week, on the same day each week48 weeks (Phase 2 reference); 68-72 weeks (Phase 3 TRIUMPH reference) · Every 4 weeks at each dose step; review at 4 mg, 9 mg, 12 mg; slow titration option adds 2-4 weeks per dose step when GI symptoms persist
Route: Subcutaneous injection
Reported by: Peptide Dosing Protocols
What it saysHide
(secondary reference; provider confirmation required). Retatrutide is dosed once weekly via subcutaneous injection starting at 1 mg and titrating up every 4 weeks to a maximum of 12 mg following the Phase 3 TRIUMPH schedule.

1-12 mg

Frequency: Once weekly · Any time of dayTitrate over weeks per response/tolerance
Route: subcutaneous
Reported by: Reference titration range, provider confirm

Reconstitution, as reported

10 mg vial with 2.0 mL BAC water yields a concentration of 5 mg/mL; use U-100 insulin syringes

Common questions

What is the starting dose of retatrutide?

The starting dose in clinical trials is 1 mg once weekly for the first 4 weeks, designed for tolerance rather than weight loss. The titration then steps up every 4 weeks: 1 mg – 2 mg – 4 mg – 6 mg – 9 mg – 12 mg in the Phase 3 TRIUMPH protocol.

What is the half-life of retatrutide?

Retatrutide's half-life is about 6 days (around 144 hours), which is why once-weekly dosing is used. After stopping, it takes roughly 5 half-lives (about 30 days) to clear. The long half-life is due to albumin binding via a C20 fatty diacid attachment.

How much weight loss does retatrutide produce in trials?

In Phase 2 (NEJM 2023), the 12 mg arm averaged 24.2% body weight loss at 48 weeks. In Phase 3 TRIUMPH-4, the 12 mg arm averaged 28.7% at 68 weeks. In Phase 3 TRIUMPH-1, the 12 mg arm averaged 28.3% at 80 weeks (a higher-BMI subgroup reached 30.3% at 104 weeks). In TRANSCEND-T2D-1, 16.8% loss was seen at 12 mg over 40 weeks in adults with type 2 diabetes.

How do you reconstitute retatrutide?

Add bacteriostatic water based on vial size and desired concentration (e.g., 10 mg vial + 2.0 mL = 5 mg/mL; 24 mg vial + 2.4 mL = 10 mg/mL). Inject BAC water down the vial wall, swirl gently (do not shake), refrigerate at 35.6–46.4°F (2–8°C), and use within 2–4 weeks.

Open the reconstitution calculator →

Is retatrutide FDA approved?

No. As of June 2026, retatrutide is not FDA-approved. It is investigational and remains in Phase 3 trials. Eli Lilly has not submitted a New Drug Application. Analyst projections place possible approval in late 2027 or 2028, but those are estimates.

What are the most common side effects of retatrutide?

The most common side effects are gastrointestinal: nausea, diarrhea, vomiting, and constipation, especially during dose escalation. In Phase 3 TRIUMPH-4, about 20.9% of participants at the highest dose reported dysesthesia (unusual skin sensitivity or tingling). Resting heart rate increased by about 5–10 bpm on average and eased over time.

How does retatrutide compare to tirzepatide and semaglutide?

Retatrutide is a triple agonist (GLP-1 + GIP + glucagon), tirzepatide is a dual agonist (GLP-1 + GIP), and semaglutide is a single agonist (GLP-1). Retatrutide has shown the highest weight loss numbers in trials so far (28.7% in TRIUMPH-4 vs. 22.5% for tirzepatide in SURMOUNT-1 and 15.8% for semaglutide in STEP-1). Retatrutide is still investigational.

Sources

01Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. New England Journal of Medicine (2023)

02Rosenstock J, Frias JP, Jastreboff AM, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. The Lancet (2023)

03Sanyal AJ, Kaplan LM, Frias JP, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine (2024)

04Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metabolism (2022)

05Eli Lilly and Company. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. PR Newswire / Eli Lilly press release (TRIUMPH-4 topline) (2025)

06Eli Lilly and Company. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. PR Newswire / Eli Lilly press release (TRIUMPH-1 topline) (2026)

07Eli Lilly and Company. Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes. PR Newswire / Eli Lilly press release (TRANSCEND-T2D-1 topline) (2026)

08Eli Lilly and Company. What to know about retatrutide. Lilly.com (2026)

09ClinicalTrials.gov. TRANSCEND-T2D-1: A Study of Retatrutide (LY3437943) in Adult Participants With Type 2 Diabetes (NCT06354660). ClinicalTrials.gov (2026)

10ClinicalTrials.gov. TRIUMPH-4: A Study of Retatrutide (LY3437943) in Participants With Obesity and Knee Osteoarthritis (NCT05929066). ClinicalTrials.gov (2025)

11Tucker ME. Triple Agonist Retatrutide Reduces A1c, Weight in T2D. Medscape (2026)

12U.S. Food and Drug Administration. Statement on FDA's review of compounded versions of brand-name GLP-1 drugs and reports of online sellers marketing unapproved peptides. FDA.gov consumer guidance (2025)