Retatrutide Q&A

Evidence

• It is a single peptide attached to a fatty acid chain, which lets it circulate for about 6 days, so one injection a week is enough.^10,15
• Lilly's code name is LY3437943. The Phase 3 obesity program is called TRIUMPH and the type 2 diabetes program is called TRANSCEND.^4,6
• Five Phase 3 readouts had been reported as of 23 Sep 2026: TRIUMPH-1, -2, -3, -4 and TRANSCEND-T2D-1.⁴

Receptor pharmacology

Compared with the body's own hormones, retatrutide is about 8.9 times as potent at the GIP receptor, 0.4 times as potent at the GLP-1 receptor and 0.3 times as potent at the glucagon receptor.¹⁰ In other words it leans heavily on GIP, with a deliberately moderate glucagon signal.

Why glucagon matters

• Energy expenditure. In fasted people, a glucagon infusion raised energy expenditure by about 230 kcal a day. The same review cautions that most mechanistic data come from rodents.⁵⁷ In mice, the glucagon component of retatrutide added to weight loss by increasing energy use.¹⁴
• Human data are pending. A Lilly study measuring calorie intake and energy expenditure on retatrutide (NCT06313528, 85 participants) finished in August 2025 but has posted no results.⁶³ The Phase 2 authors only speculated that glucagon agonism may add energy expenditure.¹⁰
• Liver fat. Glucagon drives fat burning in the liver. In the Phase 2 liver substudy, liver fat fell by 86.0% at 48 weeks on 12 mg, and 93% of that group reached normal liver fat.¹¹

What it may mean for side effects

• Glucagon and GLP-1 can both speed up the heart. In Phase 2, heart rate rose with dose, peaked at 24 weeks and then declined, which the authors called similar to GLP-1 drugs.¹⁰
• The GI side effects look like those of other incretin drugs.¹ A newer signal, dysesthesia (unusual skin sensations), has not been a prominent feature of semaglutide or tirzepatide trials. See the safety section.

• At 80 weeks the three doses produced 19.0%, 25.9% and 28.3% weight loss (efficacy estimand), or 17.6%, 23.7% and 25.0% (treatment-regimen estimand).¹
• On 12 mg the average loss was 31.9 kg (70.3 lb) from a baseline of 112.7 kg (BMI 40.0).¹
• Share losing 25% or more: 27.8%, 52.9% and 62.5% vs 2.2% on placebo. Share losing 35% or more: 5.9%, 20.8% and 27.2% vs 0.3%.¹
• Of people who started with BMI 40 or higher, 37.5% on 12 mg ended below BMI 30.¹

• An estimand is the precise definition of the treatment effect a trial is trying to measure, including how it handles events such as stopping the drug.⁵⁸
• Lilly headlines efficacy-estimand results. For TRIUMPH-1 the gap between the two is 3.3 percentage points at 12 mg (28.3% vs 25.0%).¹
• TRIUMPH-2 and TRIUMPH-3 toplines reported only efficacy-estimand figures, so treatment-regimen numbers for those trials are not yet public.⁴
• The Phase 2 NEJM paper also reported the efficacy estimand.¹⁰

N is the number randomized in the whole trial (TRIUMPH-1 extension: participants enrolled in the extension). Lilly reports 2,339 randomized in TRIUMPH-1 while the registry lists 2,335 actual enrollment; for TRIUMPH-3 Lilly reports 1,949 and the registry 1,946.^1,16,4,18 In the Phase 2 row, only the 12 mg and placebo discontinuation rates were extracted.¹⁰

• The extension enrolled 532 participants with BMI 35 or higher who completed 80 weeks and tolerated their dose. They continued for 24 more weeks, with a blinded move to the maximum tolerated dose (9 mg or 12 mg).¹
• 104-week results: 27.9%, 29.5% and 30.3% for the 4, 9 and 12 mg starting groups; the former placebo group, switched to retatrutide, lost 19.2%.¹
• Because every arm was moved up to its maximum tolerated dose after week 80, the extension does not show what a fixed dose does over two years.¹
• The claim that weight loss showed "no plateau" at 104 weeks unverified is not stated in Lilly's TRIUMPH-1 materials. In Phase 2, weight loss had not plateaued at 48 weeks.¹⁰

Placebo column uses the treatment-regimen or treatment-policy figure. In the only published head-to-head of the older two drugs, SURMOUNT-5, tirzepatide produced 20.2% weight loss vs 13.7% for semaglutide at 72 weeks.⁴⁷

• DXA substudy of the Phase 2 diabetes trial: total fat mass fell 26.1% on 8 mg and 23.2% on 12 mg at 36 weeks, vs 4.5% on placebo.¹³
• Only 103 participants had usable scans at both time points, so the estimates are imprecise.¹³
• The authors describe the proportion of lean mass lost as similar to other obesity treatments. The exact lean-mass percentage unverified could not be confirmed from the accessible abstract.¹³
• MRI in the Phase 2 liver substudy showed visceral (belly-organ) fat falling 16.1% to 48.3% at 48 weeks across doses, vs a 2.5% rise on placebo.¹¹
• The TRIUMPH-1 ADA presentation did not report body composition or liver fat.³

• TRANSCEND-T2D-1 (baseline HbA1c 7.9%): -1.7, -2.0 and -1.9 points on 4, 9 and 12 mg vs -0.8 on placebo (efficacy estimand).⁶ Treatment-regimen: -1.69, -1.86 and -1.94 vs -0.81.⁷
• Reaching HbA1c under 7.0%: 84.0%, 88.9% and 90.4% vs 52.1%. Reaching the non-diabetic range (under 5.7%): 36.6%, 45.7% and 39.0% vs 14.1%.⁸
• TRIUMPH-2 (baseline 7.7%): -1.4, -1.6 and -1.5 points vs -0.2. The largest drop was on 9 mg, not 12 mg.⁴
• TRIUMPH-1 (no diabetes): of the 36.1% with prediabetes, 88.7%, 92.1% and 95.7% returned to normal glucose vs 48.7% on placebo.³
• Phase 2 diabetes trial: HbA1c fell up to 2.02 points at 24 weeks.¹²
• No severe hypoglycemia was reported in TRANSCEND-T2D-1.⁸

• Non-HDL cholesterol fell up to 24.2% in TRIUMPH-1.²
• TRIUMPH-3 (established heart disease), 12 mg: triglycerides -37.0%, non-HDL cholesterol -16.5%, systolic BP -9.3 mmHg, waist -19.0 cm, hsCRP -51.2%. Lilly did not report 9 mg or placebo values for these.⁴
• TRANSCEND-T2D-1: triglycerides down up to 39.6%, non-HDL cholesterol up to 19.8%, systolic BP up to 6.4 mmHg.²
• TRIUMPH-4: systolic BP -14.0 mmHg on 12 mg.⁵
• Phase 2: LDL fell about 20%, and 41% (8 mg) and 30% (12 mg) of people on blood pressure drugs stopped at least one.¹⁰

• TRIUMPH-3, pooled doses vs placebo: 44 vs 52 five-component MACE events, hazard ratio 0.82 (95% CI 0.55 to 1.22); 27 vs 23 three-component MACE events, hazard ratio 1.12 (0.64 to 1.96).⁴
• Lilly said events were less frequent than anticipated in both arms.⁴
• TRIUMPH-Outcomes (NCT06383390) enrolled about 10,000 adults aged 45+ with atherosclerotic disease or chronic kidney disease; primary completion is estimated for February 2029.²¹

• Substudy of 98 people with at least 10% liver fat. Relative reduction at 24 weeks: 81.4% (8 mg) and 82.4% (12 mg); at 48 weeks: 81.7% and 86.0%, vs 4.6% on placebo.¹¹
• Normal liver fat (under 5%) at 48 weeks: 89% on 8 mg and 93% on 12 mg.¹¹
• Caveat: only 43.9% of substudy participants had a week-48 MRI.¹¹
• A master protocol (NCT07165028) is recruiting about 4,500 people with MASLD at risk of major liver outcomes; primary completion is estimated for August 2030.²³

Obstructive sleep apnea (TRIUMPH-1 basket, n=243)

• Baseline apnea-hypopnea index (AHI) was 58.6 events per hour, in the severe range.^3,50
• Change at 80 weeks: -25.7, -36.1 and -33.8 events per hour on 4, 9 and 12 mg vs -11.1 on placebo (efficacy estimand); -22.9, -34.3 and -31.7 vs -9.9 (treatment-regimen).³
• The OSA group was 63.4% male and 80.2% Hispanic, which may limit how well it represents other populations.³

Knee osteoarthritis

• TRIUMPH-4 (68 weeks): WOMAC pain fell 4.5 points (-75.8%) on 9 mg and 4.4 (-74.3%) on 12 mg from a baseline of 6.0, vs 2.4 (-40.3%) on placebo. Physical function improved by 4.1 and 4.2 points vs 2.1.⁵
• TRIUMPH-1 knee basket (n=574, 80 weeks): WOMAC pain -3.66, -4.19 and -4.30 vs -2.24.³
• Placebo groups improved substantially too, so the drug-specific effect is the difference between arms.⁵

For TRIUMPH-1 the UTI column shows Lilly's press-release figure. The ADA slide, using a single preferred term, lists 6.8%, 8.1% and 8.1% vs 4.8%.^1,3 Phase 2 dysesthesia is the "hyperesthesia or related" grouping.¹⁰

• Phase 3 therefore starts everyone at 2 mg and steps up every 4 weeks.¹
• In TRIUMPH-1, 2.2%, 3.8% and 4.6% stopped because of GI events vs 1.2% on placebo.³
• Week-by-week timing curves for Phase 3 GI events have not yet been published in a journal.
• TRIUMPH-9 (NCT07357415) is testing three different escalation schemes over 104 weeks.²⁵

• TRIUMPH-1: 5.1%, 12.3%, 12.5% vs 0.9%.¹ TRIUMPH-2: 4.5%, 5.6%, 7.3% vs 0.7%.⁴ TRIUMPH-3: 6.4%, 6.4% vs 1.3%.⁴ TRIUMPH-4: 8.8%, 20.9% vs 0.7%.⁵
• In Phase 2, skin-sensation events were 7% vs 1%; none were severe or serious and none were linked to visible skin findings.¹⁰
• The cause is not known. The rate varies widely between trials, which is one reason regulators may ask for more detail.

• UTI: TRIUMPH-1 7.5%, 8.8%, 8.4% vs 5.3%.¹ TRIUMPH-3 6.1%, 7.0% vs 5.3%.⁴ In TRIUMPH-2 the placebo rate (6.6%) was between the dose rates (3.8% to 8.0%).⁴
• Heart rate: Phase 2 showed a dose-dependent rise peaking at 24 weeks.¹⁰ The size of the rise in beats per minute unverified is not in the main paper, and Phase 3 heart-rate data have not been published. For context, labels list increases of 1 to 3 bpm for tirzepatide and 1 to 4 bpm for semaglutide.^50,51
• Arrhythmia: Phase 2 cardiac arrhythmia events were 11% on 12 mg vs 3% on placebo, mostly mild to moderate.¹⁰ In TRIUMPH-1, severe or serious arrhythmia or conduction events were 0.2%, 0.7% and 0.9% vs 0.9%.³
• Low blood pressure: hypotension-related events in TRIUMPH-1 were 2.7%, 5.3% and 8.8% vs 0.9%.³ Dizziness: 5.0%, 8.9%, 12.0% vs 3.1%.³
• Injection-site reactions: 5.5%, 8.9%, 12.2% vs 3.8%.³

• TRIUMPH-1 serious adverse events: 7.7%, 7.7%, 10.5% vs 5.5%. Deaths: 0, 3 and 1 vs 2.³
• Adjudicated pancreatitis in TRIUMPH-1: 0.2%, 0.5%, 0.7% vs 0.3%.³
• TRANSCEND-T2D-1 serious adverse events: 4.5%, 0.8%, 3.7% vs 1.5%; two deaths, both on 4 mg, judged unrelated to the drug.^8,7
• TRIUMPH-2 discontinuation was highest on 9 mg (11.6%), not 12 mg (7.7%).⁴
• In TRIUMPH-4, people with BMI 35 or higher stopped less often (8.8% and 12.1% vs 4.8%).⁵
• In TRIUMPH-3, hyperglycemia was reported less often on retatrutide (3.9%, 3.1%) than placebo (13.4%).⁴

Week ranges are derived from Lilly's description of 4-week steps.¹ Phase 2 used 1, 4, 8 and 12 mg arms with 2 mg or 4 mg starting doses.¹⁰

• TRIUMPH-3 and TRIUMPH-4 tested only 9 and 12 mg.^4,5
• Lilly highlighted that 4 mg, with a single escalation step, reached nearly 20% weight loss in TRIUMPH-1 (19.0%).¹

• TRIUMPH-6 (NCT06859268): 643 participants, Phase 3b, primary endpoint at week 116, primary completion estimated April 2028. The registry does not name the doses.²⁴
• The TRIUMPH-1 extension and the outcomes trial both use escalation to a maximum tolerated dose, suggesting a flexible approach may be studied for long-term use.^1,21
• TRIUMPH-8 (NCT07232719) tests two doses vs placebo over 56 weeks.²⁶

Common exclusions

• Weight-loss drugs, including over-the-counter products, within 90 days of screening. Earlier use of GLP-1 drugs is not listed as an exclusion in the registry summaries.^17,18,19
• Weight change of more than 5 kg (11 lb) in the prior 90 days, prior or planned bariatric surgery, type 1 diabetes, a history of pancreatitis, and a personal or family history of medullary thyroid cancer or MEN-2.^17,18
• A heart attack, stroke or heart-failure hospitalization within 90 days (TRIUMPH-3).¹⁸

Age and makeup

• Phase 3 registry records set a minimum age of 18 with no stated upper limit. Phase 2 enrolled ages 18 to 75, with BMI 27 to under 30 allowed only alongside hypertension, dyslipidemia or cardiovascular disease.^16,10,64
• TRIUMPH-4 participants averaged BMI 40.4 and 84.0% had BMI 35 or higher.⁵ TRANSCEND-T2D-1 participants averaged age 48.8 and BMI 35.8.⁷
• If your BMI is between 27 and 35, you are less represented in the pivotal data than people with severe obesity.³

Lilly's TRIUMPH-4 release prints NCT05869903, which the registry lists as a different study. TRIUMPH-4 is NCT05931367.¹⁹

• Phase 2 followed people for only 4 weeks after the last dose; TRIUMPH-2 also had a 4-week follow-up.^10,4
• STEP 1 extension: after stopping semaglutide, participants regained 11.6 of the 17.3 percentage points lost.⁴⁸
• SURMOUNT-4: people switched from tirzepatide to placebo after 36 weeks regained 14.0% of their body weight over the next 52 weeks, while those who continued lost a further 5.5%.⁴⁹
• TRIUMPH-6 includes a switch-to-placebo arm and will provide the first retatrutide withdrawal data, with primary completion estimated April 2028.²⁴

• 23 Jul 2026: Lilly said it is completing the Chemistry, Manufacturing and Controls (CMC) package required for a Biologics License Application (BLA) and plans to submit in Q1 2027.⁴
• 5 Aug 2026 (Q2 earnings): slides list retatrutide submissions for obesity, OSA and knee OA as "now expected 2027".³² On the call, Lilly restated the Q1 2027 plan.³¹
• No expedited designation (priority review or a Commissioner's National Priority Voucher) had been announced for retatrutide as of 23 Sep 2026.

Review-clock scenarios (estimates, not predictions)

Scenario dates are this page's arithmetic from FDA goal timelines, labeled estimates. Actual timing depends on FDA acceptance, review questions, possible advisory committees and the outcome of the classification dispute below.

• FDA rules treat a chain of more than 40 amino acids as a protein; shorter peptides are regulated as drugs.⁶¹ Lilly argues retatrutide qualifies under the amino acid count rule and as analogous to a protein.³³
• A district court vacated FDA's decision and sent the "analogous to a protein" question back to the agency; Lilly appealed. A BLA brings 12 years of market exclusivity.³³
• The appeals court hearing was reported as scheduled for 24 Sep 2026 unverified.³⁴

• The initial TRIUMPH program enrolled more than 5,800 participants across four registrational trials.⁴
• Submissions slipped from 2026 to 2027 while the CMC package is completed.^32,4
• Areas likely to draw regulatory questions, in this page's reading of the data: dysesthesia, the higher discontinuation rates on 12 mg, heart rate and arrhythmia, and hypotension.^1,3,5,10

What remains unproven

• Cardiovascular and kidney outcome benefit (TRIUMPH-Outcomes, about 2029).²¹
• Superiority over tirzepatide (TRIUMPH-5, primary completion estimated Nov 2026).²⁰
• Long-term safety beyond about two years, and weight maintenance (TRIUMPH-6, about 2028).²⁴

• Lilly's expanded access program (NCT07629401) is for adults with BMI 35 or higher despite the highest available dose of approved weight treatment, who have two or more serious obesity complications and cannot join a trial. A physician must request it.²⁷

• In a September 2025 warning letter, FDA explained that retatrutide is not eligible for compounding under either section 503A or 503B.³⁸
• Compounded semaglutide and tirzepatide were tolerated only during shortages; FDA declared those shortages resolved on 19 Dec 2024 (tirzepatide) and 21 Feb 2025 (semaglutide).⁴² Retatrutide never had that status.

• FDA warning letters to "research use only" retatrutide sellers include Gram Peptides (31 Mar 2026) and Peptide Partners and Royal Peptides (both 24 Aug 2026).^62,39,40
• Lilly reported filing 6 lawsuits against sellers in August 2026.³⁵
• When researchers bought semaglutide from illegal online pharmacies, purity was 7.7% to 14.37% and every sample contained endotoxin, although only 3 vials were tested. No published purity study of online retatrutide was found.⁴¹

Open the ClinicalTrials.gov search for recruiting retatrutide trials

Trial status changes often. Check the registry directly and ask the site listed there; never pay a third party to "place" you in a trial.

• Zepbound's $449 applies to the 7.5 to 15 mg doses when refilled within 45 days; otherwise higher doses cost $499 to $699.⁵³
• The November 2025 agreements set a $50 Medicare copay for covered obesity drugs.⁵² Whether retatrutide would join such arrangements is unknown.
• Coverage for obesity drugs varies widely by employer plan and state program; expect prior authorization if covered.

• Peer review: only TRANSCEND-T2D-1 has a Phase 3 journal paper (The Lancet, June 2026).⁷ Lilly says TRIUMPH-2 and -3 details will be presented at future meetings and published.⁴
• Head-to-head: TRIUMPH-5 vs tirzepatide (primary completion Nov 2026) and TRANSCEND-T2D-2 vs semaglutide (primary completion Aug 2026, no results announced).^20,29
• Outcomes: heart and kidney events (TRIUMPH-Outcomes, Feb 2029) and liver outcomes (MASLD protocol, Aug 2030).^21,23
• Mechanism: human energy-expenditure results (NCT06313528) are not posted.⁶³
• Safety detail: the cause and long-term course of dysesthesia; Phase 3 heart rate; body composition in Phase 3.^1,3
• Chronic low back pain: TRIUMPH-7 reports around September 2027.²²

1. 18 Aug 2022Preclinical and Phase 1 profile published in Cell Metabolism.¹⁴
2. 26 Jun 2023Phase 2 obesity (NEJM, 24.2% at 48 weeks on 12 mg) and Phase 2 diabetes (Lancet) results.^9,12
3. 10 Jun 2024Liver fat substudy in Nature Medicine.¹¹
4. 30 Jun 2025DXA body-composition substudy published.¹³
5. 11 Dec 2025TRIUMPH-4 topline, first Phase 3 readout (28.7% at 68 weeks).⁵
6. 19 Mar 2026TRANSCEND-T2D-1 topline (HbA1c up to -2.0 points).⁶
7. 21 May 2026TRIUMPH-1 topline (28.3% at 80 weeks on 12 mg).¹
8. 5 Jun 2026Expanded access record posted (NCT07629401).²⁷
9. 6 Jun 2026Full TRIUMPH-1 and TRANSCEND-T2D-1 data at ADA; TRANSCEND-T2D-1 published in The Lancet.^2,7
10. 23 Jul 2026TRIUMPH-2 and TRIUMPH-3 toplines; Q1 2027 US submission plan.⁴
11. 5 Aug 2026Q2 earnings: submissions "now expected 2027"; BioSpace reports on the drug-versus-biologic dispute.^32,33
12. 12 Aug 2026Lilly announces lawsuits against illegal sellers.³⁵
13. 24 Aug 2026FDA warning letters to research-peptide sellers.^39,40
14. 15 Sep 2026Lilly announces an EASD symposium on 30 Sep 2026 in Milan featuring TRIUMPH-2.³⁶
15. 23 Sep 2026This page last verified against the sources below.