Retatrutide: Product Overview
Retatrutide (LY3437943) is an investigational once-weekly injectable peptide developed by Eli Lilly. It activates three hormone receptors, GLP-1, GIP and glucagon, and is being studied for obesity, type 2 diabetes and related metabolic conditions. Lilly has reported results from five Phase 3 trials.
Product profile
| Attribute | Detail |
|---|---|
| Generic name | Retatrutide |
| Development code | LY3437943 |
| Developer | Eli Lilly and Company |
| Drug class | Triple hormone receptor agonist (incretin-based) |
| Receptor targets | GLP-1, GIP and glucagon |
| Molecule type | Single acylated peptide |
| Route | Subcutaneous injection |
| Dosing frequency | Once weekly |
| Doses studied in Phase 3 | 4 mg, 9 mg and 12 mg |
| Titration in trials | Start at 2 mg, step up every 4 weeks (2, 4, 6, 9, 12 mg) to the target dose |
| Conditions studied | Obesity and overweight, type 2 diabetes, knee osteoarthritis pain, obstructive sleep apnea, cardiovascular disease, fatty liver disease |
| Development stage | Phase 3, investigational |
| Informal names | “Triple G.” It’s also called “GLP-3” online, but no hormone by that name exists. |
Mechanism of action
Retatrutide is one molecule that copies the action of three gut and metabolic hormones. Earlier incretin medicines act on one or two of these receptors.
| Medicine | GLP-1 | GIP | Glucagon |
|---|---|---|---|
| Semaglutide | Yes | No | No |
| Tirzepatide | Yes | Yes | No |
| Retatrutide | Yes | Yes | Yes |
GLP-1 receptor. Acts on appetite centers in the brain and slows gastric emptying, so food intake drops and fullness lasts longer.
GIP receptor. Supports glucose-dependent insulin release from the pancreas after meals and influences how fat tissue stores and handles energy.
Glucagon receptor. Signals the liver to release and use stored energy. Researchers believe this arm raises energy expenditure and increases fat oxidation in the liver, which would add to the reduced intake driven by GLP-1. It’s also the likely source of side effects seen more with retatrutide than with older drugs, such as a higher resting heart rate and dysesthesia.
No published trial has compared retatrutide head to head with semaglutide or tirzepatide.
Clinical trial program
Retatrutide has met its primary endpoints in every Phase 3 trial reported so far. Weight figures below are the mean change at the highest dose versus placebo, using the efficacy estimand (participants who stayed on treatment) unless noted.
| Trial | Phase | Population | Participants | Duration | Highest-dose result |
|---|---|---|---|---|---|
| Phase 2 obesity trial | 2 | Obesity or overweight, no diabetes | 338 | 48 weeks | -24.2% body weight at 12 mg vs -2.1% |
| Phase 2a liver sub-study | 2a | Obesity with liver fat of 10% or more | 98 | 48 weeks | -86.0% relative liver fat at 12 mg vs -4.6% |
| TRIUMPH-4 | 3 | Obesity or overweight with knee osteoarthritis | 405 | 68 weeks | -28.7% body weight at 12 mg |
| TRIUMPH-1 | 3 | Obesity or overweight, no diabetes | 2,339 | 80 weeks | -28.3% body weight at 12 mg vs -2.2% |
| TRIUMPH-2 | 3 | Obesity or overweight with type 2 diabetes | 1,152 | 80 weeks | -20.8% body weight at 12 mg vs -4.0%; A1C down up to 1.6 points |
| TRIUMPH-3 | 3 | Severe obesity with established cardiovascular disease | 1,949 | 80 weeks | -22.6% body weight at 12 mg vs -3.2% |
TRANSCEND-T2D-1, a 40-week Phase 3 trial in type 2 diabetes, reported -16.8% body weight at 12 mg. Phase 3 programs in chronic low back pain, cardiovascular and renal outcomes, and fatty liver disease are ongoing.
TRIUMPH-1 and TRIUMPH-2 were published on September 29, 2026, in the New England Journal of Medicine and The Lancet respectively. TRANSCEND-T2D-1 appeared in The Lancet in June 2026.
TRIUMPH-1 in detail
TRIUMPH-1 is the largest retatrutide trial to date. Participants averaged 112.7 kg at baseline with a mean BMI of 40.0, and were randomized 1:1:1:1 to 4 mg, 9 mg, 12 mg or placebo for 80 weeks.
Results are reported two ways. The treatment-regimen estimand counts every participant who started, including those who stopped treatment, and is the primary result in the NEJM paper. The efficacy estimand estimates the effect had everyone stayed on treatment, and is the figure used in Lilly’s topline announcement.
| Group | Weight change, treatment-regimen | Weight change, efficacy | Lost 30% or more of body weight |
|---|---|---|---|
| Retatrutide 4 mg | -17.6% | -19.0% | 15.3% |
| Retatrutide 9 mg | -23.7% | -25.9% | 37.9% |
| Retatrutide 12 mg | -25.0% | -28.3% | 45.3% |
| Placebo | -3.9% | -2.2% | 0.5% |
At 80 weeks, 65.3% of participants on 12 mg had a BMI below 30.
104-week extension. 532 participants who started with a BMI of 35 or more continued for another 24 weeks, escalating to their maximum tolerated dose (9 or 12 mg). Mean weight change at 104 weeks was -27.9%, -29.5% and -30.3% for the groups originally assigned 4, 9 and 12 mg, and -19.2% for those switched from placebo.
Knee osteoarthritis basket (574 participants). Reductions in WOMAC knee pain score exceeded the 4-point clinically meaningful threshold, reaching more than 70%.
Obstructive sleep apnea basket (243 participants). Reductions in the apnea-hypopnea index exceeded 15 events per hour, reaching more than 60%.
Cardiometabolic markers. Lilly reported improvements in waist circumference, non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein.
Safety and tolerability
The safety profile is broadly consistent with other incretin-based medicines. Gastrointestinal effects are the most common, are mostly mild to moderate, and cluster during dose escalation. In the Phase 2 trial, starting at 2 mg instead of 4 mg partly reduced them.
Most common adverse events in TRIUMPH-1
| Adverse event | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Nausea | 28.6% | 38.4% | 42.4% | 14.8% |
| Diarrhea | 25.2% | 34.1% | 32.0% | 13.5% |
| Constipation | 23.8% | 25.9% | 26.1% | 10.9% |
| Vomiting | 10.6% | 22.8% | 25.3% | 4.8% |
| Dysesthesia | 5% | 12% | 13% | 1% |
| Stopped treatment due to adverse events | 4.1% | 6.9% | 11.3% | 4.9% |
Any treatment-emergent adverse event was reported by 87% to 89.2% of retatrutide participants and 80.7% on placebo, according to the TRIUMPH-1 presentation at ADA 2026.
Dysesthesia across the TRIUMPH trials
Dysesthesia, a burning, tingling or oversensitive feeling on the skin, isn’t a recognized effect of GLP-1 or GIP medicines. The glucagon component is the working explanation. Lilly’s medical information team reports events were mostly mild to moderate.
| Trial | 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| TRIUMPH-1 | 5% | 12% | 13% | 1% |
| TRIUMPH-2 | 4% | 6% | 7% | 1% |
| TRIUMPH-3 | Not studied | 6% | 6% | 1% |
| TRIUMPH-4 | Not studied | 9% | 21% | 1% |
Discontinuation in other trials. Stopping due to adverse events was 3.8%, 11.6% and 7.7% at 4, 9 and 12 mg in TRIUMPH-2 (placebo 4.9%), and 9.8% and 13.5% at 9 and 12 mg in TRIUMPH-3 (placebo 4.8%), per Lilly’s TRIUMPH-2 and TRIUMPH-3 results.
Heart rate. In the Phase 2 trial, resting heart rate rose with dose, peaked at about 24 weeks and declined afterward.
Blood pressure. Hypotension was an adverse event of special interest in TRIUMPH-1 and was more common in participants taking antihypertensive medicines.
Other adverse events of special interest in TRIUMPH-1 included injection site reactions and gastrointestinal events.
This article is for educational purposes only and does not replace medical advice. Speak with your licensed physician about weight management options that are available to you in the Philippines and suited to your health history.
