Metabolic & weight

Retatrutide

Also called LY3437943, triple agonist, GGG agonist

Retatrutide is an experimental weekly shot from Eli Lilly that acts on three hormone receptors: GIP, GLP-1, and glucagon. In its first phase 3 trial, people on the top dose lost about 28% of body weight in 80 weeks. It is not approved; Lilly plans to file with the FDA in early 2027.

Late-stage trialsTested in large human trials (phase 2b/3) but not yet approved in the US.

All printable flashcards

Illustrative chain. The exact sequence has not been published in a source we could verify.

Overview

How it works

Established in trials as a triple agonist of the GIP, GLP-1, and glucagon receptors. GLP-1 and GIP action reduce appetite and improve insulin release. Glucagon receptor action is proposed to raise energy use and liver fat burning, which may explain the large weight and liver-fat reductions. The exact contribution of each receptor in humans is still being studied.

What research shows

Phase 2 RCT (n=338, 48 weeks, NEJM 2023): weight change −8.7% (1 mg), −17.1% (4 mg), −22.8% (8 mg), −24.2% (12 mg) vs −2.1% with placebo.
TRIUMPH-1 phase 3 RCT (n=2,339, 80 weeks): −19.0% (4 mg), −25.9% (9 mg), −28.3% (12 mg); in a 104-week extension the 12 mg group reached −30.3%.
TRIUMPH-2 phase 3 RCT in type 2 diabetes (n=1,152, 80 weeks): weight −12.7% to −20.8% vs −4.0% placebo; HbA1c fell 1.4–1.6 points.
TRIUMPH-3 phase 3 RCT in people with heart disease (n=1,949, 80 weeks): −21.6% (9 mg) and −22.6% (12 mg) vs −3.2% placebo; cardiovascular effect inconclusive (MACE-3 HR 1.12, wide CI).

Doses studied in people

Study or label	Dose used	Source
Phase 2 RCT in obesity (n=338)	1, 4, 8, or 12 mg once weekly, subcutaneous (starting doses 2 or 4 mg for higher arms), 48 weeks	¹
TRIUMPH-1 phase 3 RCT in obesity (n=2,339)	Start 2 mg, escalate to 4, 9, or 12 mg once weekly, subcutaneous, 80 weeks	²
TRIUMPH-2 phase 3 RCT in type 2 diabetes (n=1,152)	Start 2 mg, escalated every 4 weeks to 4, 9, or 12 mg once weekly, 80 weeks	⁴
TRIUMPH-3 phase 3 RCT in cardiovascular disease (n=1,949)	Start 2 mg, escalated every 4 weeks to 9 or 12 mg once weekly, 80 weeks	⁴

No approved dose exists; the doses listed are only those tested in published or announced clinical trials.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Weekly protocol

How the schedule looks week by week. Each chart says where it comes from: a prescribing label, a clinical trial, or a protocol commonly reported online.

Phase 2 obesity trial (12 mg arm)

Clinical trial

One week

D1D2D3D4D5D6D7

Once weekly · Subcutaneous injection

Syringe units (U-100)

Vial Water added

Dose by week

2 mgwk 1–4

4 mgwk 5–8

8 mgwk 9–12

12 mgMaintenance · wk 13–48

Supplies for one course (estimate)

Counts only. This site does not sell or link to supplies.

Course: 48 weeks
Note: Other arms stopped at 4 mg or 8 mg (some started at 4 mg). Phase 3 TRIUMPH trials also start at 2 mg with 4-week steps. Investigational; not approved.
Source: Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity, phase 2 (NEJM 2023); trial protocol NCT04881760

Reference only, not a recommendation. Label and trial schedules were set for specific patients under medical supervision. Use the calculator only to understand the arithmetic.

Vial math

Many research vials hold 5 or 10 mg of powder. This table shows how much ends up in each mark on a U-100 insulin syringe for common amounts of added liquid. It is arithmetic only, not a dose.

Vial	Liquid added	Concentration	Per unit (0.01 mL)
5 mg	1 mL	5 mg/mL	50 mcg	Open in calculator
5 mg	2 mL	2.5 mg/mL	25 mcg	Open in calculator
5 mg	3 mL	1.67 mg/mL	16.7 mcg	Open in calculator
10 mg	1 mL	10 mg/mL	100 mcg	Open in calculator
10 mg	2 mL	5 mg/mL	50 mcg	Open in calculator
10 mg	3 mL	3.33 mg/mL	33.3 mcg	Open in calculator

More sizes: all vial sizes · How this works: Syringes and units · Reconstitution guide.

Safety

GI side effects were common and dose-related in TRIUMPH-1: nausea up to 42% and vomiting up to 25% at 12 mg (placebo 15% and 5%).
Stopping due to side effects rose with dose: 11.3% at 12 mg in TRIUMPH-1 and 13.5% at 12 mg in TRIUMPH-3 (placebo about 5%).
Dysesthesia (abnormal skin sensations) occurred in about 4.5–7.3% on retatrutide vs about 1% on placebo in TRIUMPH-2 and -3; mostly mild to moderate.
Phase 2 showed dose-dependent heart-rate increases that peaked around week 24.
Long-term safety and cardiovascular effects are not yet established.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA: Investigational; not FDA-approved. Lilly plans to submit an application in Q1 2027.
Compounding: Not lawful to compound: FDA considers retatrutide an investigational ingredient that cannot be used in compounding. Products sold online as 'research' retatrutide are unapproved.
Sports (WADA): Not named on the WADA list; as an unapproved drug it would fall under S0 (non-approved substances, prohibited at all times) — confirm with your anti-doping body.
Other: Not a controlled substance.

Rules change often. See Legal status of peptides for how these categories work.

History

Discovered by Eli Lilly. The phase 2 obesity trial was published in NEJM in June 2023. The phase 3 TRIUMPH program reported TRIUMPH-1 (obesity) topline results on May 21, 2026, and TRIUMPH-2 (type 2 diabetes) and TRIUMPH-3 (established cardiovascular disease) on July 23, 2026. Lilly says it plans to submit a Biologics License Application to the FDA in Q1 2027 after completing its manufacturing data package.

Common questions

Is retatrutide FDA-approved?

No. It is still investigational, and Lilly plans to submit an application to FDA in early 2027 ⁴.

How is it different from GLP-1 drugs?

It acts on three hormone receptors at once: GIP, GLP-1 and glucagon ¹. The glucagon part is thought to raise energy use and liver fat burning, but each receptor's role in people is still being studied ¹.

What does the research show?

In the TRIUMPH-1 phase 3 trial (2,339 people, 80 weeks), weight fell 19.0% to 28.3% depending on dose, and the 12 mg group reached 30.3% in a 104-week extension ². In people with heart disease, its effect on heart events was inconclusive ⁴.

What doses were studied?

Phase 3 trials started at 2 mg weekly and stepped up to 4, 9 or 12 mg once weekly by injection ²⁴. There is no approved dose; these are trial doses only.

What are the side effects?

Stomach side effects were common and rose with dose; at 12 mg in TRIUMPH-1, nausea reached 42% and vomiting 25%, vs 15% and 5% on placebo ². Some people also reported abnormal skin sensations, and the phase 2 trial saw heart-rate increases ⁴¹.

Is 'research' retatrutide sold online legal?

No. FDA considers retatrutide an investigational ingredient that cannot be used in compounding, and products sold online as 'research' retatrutide are unapproved ⁵⁶.

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Sources

Last reviewed 2026-10-25 · How we research · Found an error? See our corrections policy.