Frequently Asked Questions

Retatrutide (LY3437943) is an investigational medication developed by Eli Lilly and Company. It is a single peptide molecule that simultaneously activates three metabolic hormone receptors: GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1), and glucagon receptors. This triple receptor agonism is a novel approach designed to address obesity and type 2 diabetes through complementary metabolic pathways.

No. As of October 31, 2026, retatrutide is an investigational compound in late-stage Phase 3 clinical development. It has not been approved by the FDA or any other regulatory authority worldwide. Six Phase 3 trials have reported positive topline results: TRIUMPH-4 (Dec 2025), TRANSCEND-T2D-1 (March 19, 2026), TRIUMPH-1 (May 21, 2026), TRIUMPH-2 and TRIUMPH-3 (July 23, 2026) and the head-to-head TRANSCEND-T2D-2 against Ozempic (October 28, 2026). No application has been filed yet. Lilly says it plans to file for approval no later than the first quarter of 2027. On October 2, 2026 the FDA ruled that the application must be a New Drug Application (NDA); Lilly disputes that in court and has not said which pathway it will use. The drug is not available for prescription or commercial purchase. Any legitimate use is limited to authorized clinical trials.

Retatrutide is being developed by Eli Lilly and Company, a major pharmaceutical company based in Indianapolis, Indiana. Lilly also developed tirzepatide (marketed as Mounjaro for type 2 diabetes and Zepbound for obesity), which is a related dual GIP/GLP-1 receptor agonist.

LY3437943 is retatrutide's development code assigned by Eli Lilly. The 'LY' prefix identifies it as a Lilly compound, and the numerical designation is its internal identifier. 'Retatrutide' is the drug's International Nonproprietary Name (INN), which is the standardized name for scientific and medical communication.

Retatrutide is primarily being studied for the treatment of obesity and weight management in the Phase 3 TRIUMPH program (4 trials: TRIUMPH-1 through TRIUMPH-4, plus TRIUMPH-Outcomes for cardiovascular events). The separate TRANSCEND program (TRANSCEND-T2D-1, T2D-2, T2D-3, CKD) evaluates retatrutide for type 2 diabetes. It is also being evaluated for metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) in dedicated trials: the SYNERGY trial and the MACELD Phase 3 trial, which launched in Q4 2025. The Phase 2 data showed significant liver fat reduction with 86% of participants at the 12 mg dose achieving normal liver fat levels, supporting the dedicated liver disease program.

Semaglutide (Ozempic/Wegovy) targets only the GLP-1 receptor. Tirzepatide (Mounjaro/Zepbound) targets both GIP and GLP-1 receptors. Retatrutide targets all three: GIP, GLP-1, and glucagon receptors. The addition of glucagon receptor agonism is hypothesized to increase energy expenditure and promote liver fat reduction, which are effects not available from single or dual agonists.

No. Retatrutide does not have a brand name because it has not received marketing authorization from any regulatory agency. Brand names are typically assigned during the regulatory approval process. The drug is referred to by its INN (retatrutide) or development code (LY3437943) in scientific literature.

On July 23, 2026, with all five pivotal trials reported (TRIUMPH-4, TRANSCEND-T2D-1, TRIUMPH-1, TRIUMPH-2 and TRIUMPH-3), Eli Lilly said it planned to submit a Biologics License Application to the FDA in the first quarter of 2027. Lilly says it plans to file for approval no later than the first quarter of 2027. On October 2, 2026 the FDA ruled that the application must be a New Drug Application (NDA); Lilly disputes that in court and has not said which pathway it will use. On our estimate, an FDA decision could come in late 2027 with priority review, or around the first quarter of 2028 under standard review. These are our estimates, not Lilly's, and depend on the FDA's filing decision and review.

A triple agonist is a single molecule that activates three different receptor types. Retatrutide activates GIP receptors, GLP-1 receptors, and glucagon receptors. Each receptor triggers different biological effects, and their simultaneous activation produces complementary metabolic benefits that are hypothesized to be greater than any single receptor pathway alone.

GLP-1 receptor activation reduces appetite through effects on brain satiety centers, stimulates insulin secretion in a glucose-dependent manner (lowering blood sugar without causing dangerous drops), suppresses glucagon release from the pancreas, and slows gastric emptying. This is the same mechanism used by approved drugs like semaglutide (Ozempic/Wegovy) and liraglutide (Saxenda).

GIP receptor activation enhances insulin secretion, influences adipose (fat) tissue function, and may contribute to appetite suppression through brain pathways. When combined with GLP-1 receptor activation, GIP appears to amplify the metabolic benefits, as demonstrated by tirzepatide (Mounjaro/Zepbound), which targets both GIP and GLP-1 receptors.

Glucagon receptor activation increases energy expenditure (the number of calories the body burns at rest) and promotes fatty acid oxidation in the liver (burning stored fat for energy). This component is unique to retatrutide among advanced clinical candidates and is thought to explain the enhanced weight loss and dramatic liver fat reduction observed in clinical trials.

Glucagon naturally raises blood glucose by stimulating the liver to release stored sugar. In retatrutide, this glucose-raising effect is counterbalanced by the simultaneous GLP-1 and GIP receptor activation, which promote insulin secretion and suppress excessive glucagon signaling. Clinical trial data confirm that the net effect is improved, not worsened, blood sugar control.

Retatrutide's peptide structure includes a fatty acid modification that allows it to bind to albumin, a protein in the blood. This albumin binding protects the drug from being broken down quickly and extends its half-life to approximately six days, meaning that a single injection provides sustained drug levels throughout a full week.

Retatrutide promotes weight loss through two complementary mechanisms: reducing caloric intake (through appetite suppression mediated by GLP-1 and GIP receptor activation in the brain) and increasing caloric expenditure (through energy expenditure increases driven by glucagon receptor activation). This dual approach to the energy balance equation distinguishes it from single- and dual-agonist therapies that primarily reduce intake.

As of October 31, 2026, retatrutide has completed Phase 1, Phase 2, and all five pivotal Phase 3 trials with positive topline results: TRIUMPH-4 (obesity + knee osteoarthritis, December 2025, -28.7% at 12 mg/68 weeks), TRANSCEND-T2D-1 (type 2 diabetes, March 2026, published in The Lancet June 6, 2026), TRIUMPH-1 (obesity, May 21, 2026, -28.3% at 12 mg/80 weeks), TRIUMPH-2 (obesity + type 2 diabetes, July 23, 2026, -20.8%) and TRIUMPH-3 (severe obesity + cardiovascular disease, July 23, 2026, -22.6%). The head-to-head TRANSCEND-T2D-2 trial against semaglutide 2 mg reported topline results on October 28, 2026. TRIUMPH-5 (vs tirzepatide), the TRIUMPH-Outcomes cardiovascular trial, TRANSCEND-T2D-3 and the SYNERGY/MACELD liver trials are still running.

The Phase 2 obesity trial demonstrated mean weight loss of up to 24.2% at 48 weeks in the highest dose group (12 mg), with 100% of participants at that dose losing at least 5% of body weight. In a liver substudy, liver fat fell by about 82% (relative) at 24 weeks on 12 mg. The trial also showed improvements in blood pressure and lipids, and a manageable gastrointestinal side effect profile. These were the highest weight loss results ever reported for a pharmacological agent.

The Phase 2 type 2 diabetes trial (281 adults) showed HbA1c reductions of up to 2.02 percentage points at 24 weeks, the primary endpoint, in the 12 mg group, versus 1.41 with dulaglutide 1.5 mg and 0.01 with placebo. Between 53% and 86% of participants on 4 mg or more reached an HbA1c of 7.0% or less at 24 weeks, against 22% on placebo. The 8 mg (2 mg start) and 12 mg groups lowered HbA1c significantly more than dulaglutide, and body weight fell by up to 16.9% at 36 weeks.

TRIUMPH is the name of Lilly's Phase 3 program for retatrutide in obesity and weight management; Lilly does not give it an expanded form. The initial program had four registrational trials: TRIUMPH-1 (obesity/overweight without T2D, with nested OSA and OA baskets), TRIUMPH-2 (obesity/overweight with T2D, with nested OSA basket), TRIUMPH-3 (Class II/III obesity with established cardiovascular disease), and TRIUMPH-4 (obesity with knee osteoarthritis, completed December 2025). TRIUMPH-5 compares retatrutide with tirzepatide, and TRIUMPH-Outcomes is a separate 10,000-patient cardiovascular outcomes trial. The separate TRANSCEND program addresses the standalone T2D indication.

All five pivotal readouts are in: TRIUMPH-4 (December 2025), TRANSCEND-T2D-1 (March 19, 2026), TRIUMPH-1 (May 21, 2026), and TRIUMPH-2 and TRIUMPH-3 (July 23, 2026). Peer-reviewed papers have followed for TRANSCEND-T2D-1 (The Lancet, June 6, 2026), TRIUMPH-1 (NEJM, September 29, 2026) and TRIUMPH-2 (The Lancet, September 29, 2026); TRIUMPH-3 has no paper yet. TRANSCEND-T2D-2, the first head-to-head trial against semaglutide 2 mg (Ozempic), reported topline results on October 28, 2026: at 80 weeks retatrutide 12 mg lowered A1C by 2.2 points vs 1.8 with semaglutide 2 mg, and body weight by 20.9% vs 9.4% (not yet peer reviewed). Still to come: TRIUMPH-5 (vs tirzepatide, primary completion expected November 2026), TRIUMPH-Outcomes (cardiovascular outcomes) and the SYNERGY/MACELD liver trials.

Yes, since August 2026, and it is narrow. Eli Lilly runs a single-patient expanded access program (ClinicalTrials.gov NCT07629401) for adults with a BMI of 35 or higher despite the highest dose of an approved weight-management drug, two or more serious obesity-related complications, and no accessible clinical trial. Only a treating physician can request it, through the Lilly Answers Center (1-800-545-5979), and meeting the criteria does not guarantee supply.

This resource does not facilitate clinical trial enrollment. If you are interested in participating in a clinical trial, discuss this with your healthcare provider or search for registered studies on ClinicalTrials.gov using the search term 'retatrutide' or 'LY3437943'. Eligibility criteria vary by trial and are determined by the study investigators.

In Phase 2 clinical trials, the most commonly reported side effects were gastrointestinal in nature: nausea, diarrhea, vomiting, constipation, and decreased appetite. These effects are consistent with the known pharmacology of GLP-1 receptor agonists and were predominantly mild to moderate in severity. Most GI events occurred during the dose-escalation period and diminished over time as participants adapted to the medication.

In the 48-week Phase 2 obesity trial, 6% to 16% of participants in the retatrutide groups stopped treatment because of adverse events (16% at 12 mg), against none on placebo. In the 68-week Phase 3 TRIUMPH-4 trial the rates were 4.0% with placebo, 12.2% with 9 mg and 18.2% with 12 mg. In the 80-week TRIUMPH-1 trial they were 4.1% (4 mg), 6.9% (9 mg) and 11.3% (12 mg), against 4.9% on placebo. Gastrointestinal events were the most common reason. For comparison, the US labels report 6.8% for semaglutide 2.4 mg and up to 6.7% for tirzepatide. In Phase 2, starting at 2 mg rather than 4 mg lowered nausea.

In the Phase 2 obesity trial (participants without diabetes), no significant hypoglycemia was reported. In the type 2 diabetes trial, hypoglycemia rates were low and were primarily associated with concomitant use of other diabetes medications (such as sulfonylureas) that can independently cause low blood sugar. Retatrutide's insulin-promoting effects are glucose-dependent, meaning they are activated mainly when blood sugar is elevated, which inherently reduces hypoglycemia risk.

Retatrutide raises heart rate, a known effect of GLP-1 receptor agonists. In the Phase 2 obesity trial, heart rate rose with dose, peaked at 24 weeks and then declined; the authors described the increases as similar to those reported for GLP-1 receptor agonists. Blood pressure and lipid profiles improved with treatment, which are favorable cardiovascular signals. However, no dedicated cardiovascular outcomes trial has been completed for retatrutide, so definitive cardiovascular safety or benefit data are not yet available.

The longest treatment durations reported so far are 80 weeks in the Phase 3 TRIUMPH-1, TRIUMPH-2 and TRIUMPH-3 trials and in TRANSCEND-T2D-2, with a 104-week extension in a TRIUMPH-1 subgroup. Long-term safety data over multiple years, which are essential for a medication intended for chronic use, will be generated by the broader Phase 3 TRIUMPH program and post-marketing surveillance if the drug is approved. Long-term effects on bone density, muscle mass, nutritional status, and organ function require continued study.

No unexpected serious safety signals were reported in the Phase 2 retatrutide trials. However, Phase 3 TRIUMPH-4 data (December 2025) identified a new signal: dysesthesia (abnormal skin sensations such as tingling, numbness or burning), reported in 8.8% of the 9 mg group and 20.9% of the 12 mg group, compared with 0.7% for placebo. This signal was not prominent in Phase 2 data and is thought to be linked to glucagon receptor activity. Later Phase 3 trials reported lower rates at 12 mg: 12.5% in TRIUMPH-1, 7.3% in TRIUMPH-2 and 6.4% in TRIUMPH-3. Dysesthesia was generally mild and infrequently led to discontinuation. The broader safety profile remains consistent with the known effects of incretin-based therapies, though Phase 3 trials with larger populations continue to provide a more comprehensive safety assessment.

Retatrutide is not currently available for prescription or purchase. Its pivotal Phase 3 trials have all reported, and no application has been filed yet. Lilly says it plans to file for approval no later than the first quarter of 2027. On October 2, 2026 the FDA ruled that the application must be a New Drug Application (NDA); Lilly disputes that in court and has not said which pathway it will use. (In July 2026 Lilly had said it planned a Biologics License Application.) On our estimate, an FDA decision could come in late 2027 with priority review, or around the first quarter of 2028 with standard review.

The main legitimate way to receive retatrutide is participation in an authorized clinical trial. Since August 2026 there is also a narrow expanded access program (NCT07629401) for adults with a BMI of 35 or higher despite maximal approved therapy and two or more serious obesity-related complications, which a treating physician must request from Eli Lilly. The drug is not approved for prescription, and purchasing it outside of a clinical trial setting is not sanctioned by regulatory authorities. We strongly advise against obtaining any investigational compound through unregulated channels.

In all clinical trials to date, retatrutide has been administered as a once-weekly subcutaneous injection. If approved, it is expected to be available initially as an injectable formulation. Whether an oral formulation might be developed in the future is unknown and would require separate clinical development.

Pricing has not been determined, as retatrutide has not been approved for marketing. For context, other incretin-based obesity medications carry US list prices above $1,000 per month (Wegovy's was $1,349 as of February 2026), though what patients pay varies widely. Self-pay prices are lower: as of October 2026, LillyDirect sells Zepbound for $299 to $449 a month depending on dose, and the Foundayo pill for $149 to $349. Retatrutide pricing will depend on its approved indications, competitive positioning, insurance coverage decisions, and Eli Lilly's pricing strategy.

Insurance coverage decisions cannot be predicted at this time. Coverage for obesity medications has historically been limited, though it has been expanding in recent years as the medical community increasingly recognizes obesity as a chronic disease requiring pharmacological treatment. Coverage will depend on the approved indications, individual insurance plans, and payer policies at the time of potential approval.

If retatrutide receives FDA approval, Eli Lilly would be expected to pursue regulatory submissions in other major markets, including the European Union (through the EMA), Japan, Canada, Australia, and other countries. International approval timelines typically lag behind U.S. approval by 6-18 months, depending on the regulatory agency and submission timing.