Eli Lilly Pipeline: What Comes After Zepbound
Lilly's next obesity drug, retatrutide, delivered 28.3% (70.3 lbs) average efficacy-estimand weight loss at 80 weeks in Phase 3, with a BLA planned for Q1 2027. Behind it sit eloralintide, bimagrumab and the already-launched pill Foundayo. Here is where each asset stands.
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Eli Lilly’s pipeline after Zepbound is led by retatrutide, an investigational once-weekly injection that activates three hormone receptors — GIP, GLP-1 and glucagon — instead of the two that Zepbound targets [1][2][5]. Topline results from TRIUMPH-1, TRIUMPH-2 and TRIUMPH-3 have been announced as positive, and Lilly says it plans to submit a Biologics License Application (BLA) to the FDA in the first quarter of 2027 [1][2][3]. In its lead trial, participants on the highest studied dose lost an average of 28.3% of body weight (70.3 lbs) over 80 weeks on the efficacy estimand [1].
Retatrutide is not approved by any regulator anywhere in the world, and the only legal way to access it is as a participant in a Lilly clinical trial [1][4]. Behind it, Lilly has eloralintide, an investigational once-weekly amylin receptor agonist that posted 20.1% average efficacy-estimand weight loss at 48 weeks in Phase 2, with Lilly saying it planned to begin Phase 3 obesity enrollment by the end of 2025 [6]; bimagrumab, a muscle-sparing candidate still in Phase 2 [7]; and Foundayo (orforglipron), a once-daily GLP-1 pill that is already marketed and booked $98 million in its first reported quarter [2][3].
What is retatrutide and how is it different from Zepbound?
Retatrutide is a first-in-class triple hormone receptor agonist — a single molecule that activates receptors for GIP, GLP-1 and glucagon [1][2]. Zepbound (tirzepatide) targets GLP-1 and GIP but not glucagon [1][5]. Both are, or would be, once-weekly injections [1][5].
Lilly is studying retatrutide in Phase 3 trials covering obesity and overweight with at least one weight-related medical problem, type 2 diabetes, knee osteoarthritis pain, moderate-to-severe obstructive sleep apnea, chronic low back pain, cardiovascular and renal outcomes, and metabolic dysfunction-associated steatotic liver disease [1][2]. The TRIUMPH Phase 3 program began in 2023 and has enrolled more than 5,800 participants across four global registrational trials [1][2].
How much weight did people lose in the retatrutide Phase 3 trials?
In TRIUMPH-1, announced May 21, 2026, participants on retatrutide 12 mg lost an average of 28.3% of body weight (70.3 lbs) at 80 weeks, compared with 2.2% (5.5 lbs) for placebo [1]. The trial randomized 2,339 adults with obesity or overweight plus at least one weight-related comorbidity and no diabetes, in a 1:1:1:1 ratio, with an average starting weight of 112.7 kg (248.5 lbs) and BMI of 40.0 [1].
These are efficacy-estimand results, meaning they represent what would have happened had all randomized participants remained on study intervention, with possible dose interruptions and modifications, without initiating prohibited weight management treatments [1]. Under the treatment-regimen estimand, the 80-week figures were 17.6% (4 mg), 23.7% (9 mg) and 25.0% (12 mg), versus 3.9% for placebo [1].
| TRIUMPH-1, efficacy estimand, 80 weeks | Retatrutide 4 mg | 9 mg | 12 mg | Placebo |
|---|---|---|---|---|
| Weight change | −19.0% (−47.2 lbs) | −25.9% (−64.4 lbs) | −28.3% (−70.3 lbs) | −2.2% (−5.5 lbs) |
| Achieved ≥30% weight loss | 15.3% | 37.9% | 45.3% | 0.5% |
| Achieved ≥25% weight loss | 27.8% | 52.9% | 62.5% | 2.2% |
| Waist circumference | −16.3 cm | −21.8 cm | −24.1 cm (−9.5 in) | −3.6 cm |
In a pre-specified 104-week extension, 532 participants with a BMI of 35 or higher at baseline who had completed the main 80-week study on their assigned dose without discontinuation or permanent dose reduction continued treatment for 24 additional weeks, including a blinded escalation to a maximum tolerated dose of 9 mg or 12 mg [1]. In the 12 mg-to-MTD arm, participants lost an average of 30.3% (85.0 lbs) at 104 weeks [1]. A pre-specified analysis found 65.3% of participants on 12 mg reached a BMI under 30 at 80 weeks, though this endpoint was not controlled for multiplicity [1]. The lead investigator was Ania Jastreboff, M.D., Ph.D., of the Yale School of Medicine [1].
Two more trials reported topline results on July 23, 2026 [2]. TRIUMPH-2 (NCT05929079) enrolled 1,152 adults with obesity or overweight and type 2 diabetes; on the efficacy estimand, at 80 weeks they lost 12.7% (29.8 lbs) on 4 mg, 19.1% (45.4 lbs) on 9 mg and 20.8% (49.6 lbs) on 12 mg, versus 4.0% on placebo, with A1C falling 1.4 to 1.6 points from a 7.7% baseline [2]. TRIUMPH-3 (NCT05882045) enrolled 1,949 adults with BMI of 35 or higher and established cardiovascular disease; efficacy-estimand weight loss was 21.6% (52.7 lbs) on 9 mg and 22.6% (55.8 lbs) on 12 mg, versus 3.2% on placebo [2].
All of these figures are averages from supervised, randomized studies with structured dose-escalation schedules built in — they describe trial populations, not what any individual person will lose [1][2].
What side effects did retatrutide cause in the trials?
The most common adverse events in TRIUMPH-1 were gastrointestinal, and they increased with dose [1].
| 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 | 5.1% | 12.3% | 12.5% | 0.9% |
| Discontinued due to adverse events | 4.1% | 6.9% | 11.3% | 4.9% |
Dysesthesia events were generally mild to moderate, mostly resolved during treatment, and most participants continued taking the drug [1]. In TRIUMPH-3, discontinuations for adverse events were 9.8% on 9 mg and 13.5% on 12 mg, versus 4.8% on placebo [2].
Did retatrutide reduce heart attacks or strokes?
TRIUMPH-3 was designed to test weight loss in people with established cardiovascular disease, and it also tracked major adverse cardiovascular events [2]. The results were not conclusive either way. For the pre-specified in-study MACE-5 analysis (all-cause death, heart attack, stroke, heart failure event or coronary revascularization), the hazard ratio was 0.82 with a 95% confidence interval of 0.55 to 1.22 — a range that includes no effect [2]. For MACE-3 (cardiovascular death, heart attack or stroke), the hazard ratio was 1.12 with a 95% confidence interval of 0.64 to 1.96 [2]. Events occurred less frequently than anticipated in both the retatrutide and placebo arms [2].
The trial did show reductions in certain cardiovascular risk factors at the highest dose, including triglycerides, non-HDL cholesterol, systolic blood pressure, waist circumference and high-sensitivity C-reactive protein [2].
When will retatrutide be approved and available in the US?
Lilly is completing its Chemistry, Manufacturing and Controls (CMC) data package and plans to submit a BLA to the FDA in Q1 2027 [2][3]. The company says its clinical data package is now complete to support global registrations in obesity, obstructive sleep apnea and knee osteoarthritis pain [2][3].
Is retatrutide legal to buy online or from a peptide seller?
No. Retatrutide cannot be legally sold or marketed for human use anywhere, to anyone, for any reason, and no medicine containing it has been approved by any regulator [2][4][5]. The FDA has stated that sales of unapproved retatrutide to consumers are illegal, that it cannot be lawfully compounded, and that so-called “research-use only” products are of unknown quality and may be harmful [4].
On August 12, 2026, Lilly filed six lawsuits against US sellers of black-market retatrutide [4][5]. The defendants are Striker Pharmacy, a suburban Houston compounding pharmacy; Aesthetic Envy, a Sacramento med spa chain; Astra Peptides of Austin; Texas Peptides and Lone Star Peptide Co. of Houston; and Legendary Peptides of Lumberton, Texas [4][5]. Lilly has reported more than 14,000 websites, ads, social media posts and product listings marketing retatrutide in over 100 countries, and has referred more than 200 individuals and entities to the FDA, the Department of Justice, state attorneys general, law enforcement and licensing boards [4][5].
Black markets for unapproved drugs can form when compounders use ingredients listed in publicly available patent documents, and the product is often sourced from China and sold through med spas, online retailers and chat groups on apps like Telegram and WhatsApp [5]. Lilly’s chief medical officer, David A. Hyman, M.D., said what is sold on the black market “is not a medicine – it is entirely unverified, unapproved and not worth the risk” [4][5]. Lilly is also calling on social media and e-commerce platforms, credit card companies, payment processors and shipping and logistics firms to cut off the trade [4][5]. Suspected illegal products can be reported to the Lilly Answers Center at 1-800-LillyRx [4].
There are signs of real harm. Australian health authorities reported six cases of liver toxicity in users of unapproved retatrutide in the summer of 2026, and the Washington Poison Center has reported rising calls related to illegal retatrutide [5]. An August preprint by three Boston-area researchers associated black-market retatrutide use with lower weight loss and increased cardiovascular symptoms [5]. Lilly spokesperson Jared Shapiro said patients have reported serious harms after taking black-market retatrutide purchased online, including hospitalizations — a company claim that has not been independently confirmed [5]. Lilly used a similar legal strategy the prior year, suing two compounding pharmacies and four telehealth companies over compounded tirzepatide [5].
What is eloralintide and how is it different from a GLP-1 drug?
Eloralintide is an investigational once-weekly selective amylin receptor agonist, formerly known as LY3841136 [6]. It works on the amylin system rather than GLP-1 or GIP, and its effects are likely mediated by affecting satiety — the feeling of fullness — and reducing calorie intake [6].
In a Phase 2 trial (NCT06230523) announced November 6, 2025, 263 US adults with obesity or overweight plus at least one comorbidity, and without type 2 diabetes, were randomized over 48 weeks [6]. Using the efficacy estimand, weight loss ranged from 9.5% (22.5 lbs) on 1 mg to 20.1% (47.0 lbs) on 9 mg, versus 0.4% on placebo, from an average baseline of 109.1 kg (240.5 lbs) [6]. Escalation arms lost 19.9% (6/9 mg) and 16.4% (3/6/9 mg) [6]. These endpoints were not adjusted for multiplicity [6].
The most common adverse events were mild-to-moderate gastrointestinal symptoms and fatigue, more frequent at higher doses; incidence was lower with slower escalation and similar to placebo in the 1 mg and 3 mg arms [6]. Results were presented at ObesityWeek 2025 and published in The Lancet [6]. Lilly said it planned to begin Phase 3 obesity enrollment by the end of 2025, and a separate Phase 2 trial (NCT06603571) is testing eloralintide alone or with tirzepatide in people with obesity or overweight and type 2 diabetes [6].
Is there a drug to prevent muscle loss on obesity medication?
Not yet. No muscle-preservation drug has been approved for use alongside obesity medication [7]. Lilly’s candidate is bimagrumab, which targets proteins that regulate muscle growth with the aim of preserving lean mass during GLP-1 weight loss [7]. Lilly acquired it by buying Versanis Bio in 2023 for up to $1.9 billion; the drug was originally discovered by Novartis and licensed to Versanis, which launched in 2021 [7].
On September 25, 2025, Lilly canceled one of two Phase 2 bimagrumab trials (NCT06901349), which included people with type 2 diabetes and was expected to enroll about 180 people with completion in late 2026, citing “strategic business reasons” [7]. The second Phase 2 trial (NCT06643728), in non-diabetic obesity, testing bimagrumab with or without Zepbound, was still recruiting, with initial results expected around April 2026 [7]. Regeneron, Biohaven, Scholar Rock and Veru also have muscle-sparing obesity candidates in development, and Veru has said the FDA now guides that incremental weight loss over a GLP-1 alone is an acceptable primary endpoint for approval — a signal of a higher bar [7].
What is Foundayo and how does it differ from Zepbound?
Foundayo (orforglipron) is a once-daily GLP-1 pill for weight management, taken by mouth rather than injected [2][5]. Its label states it is used with a reduced-calorie diet and increased physical activity in adults with obesity, or overweight with weight-related medical problems [2]. It should not be used with other GLP-1 receptor agonist medicines, and its safety and effectiveness in children have not been established [2].
Foundayo carries a boxed warning that it may cause thyroid tumors, including thyroid cancer, and is contraindicated in people with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 [2]. Serious risks listed on the label include pancreatitis [2].
Commercially, Foundayo reported $98 million in revenue in Q2 2026, its first reported quarter, and was added to Lilly’s Key Products list that quarter [3]. Lilly has also submitted orforglipron for type 2 diabetes in the US [3].
What do Lilly’s Q2 2026 results show about the pipeline?
Lilly’s Q2 2026 results show the scale of the business and spending behind the pipeline. Q2 2026 revenue was $22,974 million, up 48% year over year, driven by a 60% volume increase partly offset by a 13% decline in realized prices [3]. Mounjaro brought in $9,943 million (+91%) and Zepbound $4,928 million (+46%) [3]. Lilly raised its full-year 2026 revenue guidance to $85.0–$87.0 billion, with a non-GAAP EPS range of $35.50 to $36.50 [3].
| Q2 2026 selected product revenue | Q2 2026 | Change vs Q2 2025 |
|---|---|---|
| Mounjaro | $9,943M | +91% |
| Zepbound | $4,928M | +46% |
| Ebglyss | $201M | +131% |
| Jaypirca | $192M | +56% |
| Kisunla | $167M | NM |
| Omvoh | $102M | +36% |
| Inluriyo | $75M | NM |
| Foundayo | $98M | NM |
Lilly recognized $2.8 billion in acquired IPR&D charges in Q2 2026 ($3.03 per share), versus $154 million ($0.14) in Q2 2025 [3]. During the quarter it completed acquisitions of Orna Therapeutics, Ajax Therapeutics, Centessa Pharmaceuticals and Kelonia Therapeutics; after quarter end it completed three acquisitions to build an infectious disease portfolio and agreed to acquire AtaiBeckley [3]. It also committed an additional $4.5 billion to expand Indiana manufacturing sites [3]. R&D expense was $3.8 billion, 17% of revenue, up 14% [3]. Lilly cites an average of 10 to 15 years and $2.6 billion to develop a single FDA-approved medicine [5].
What else does Lilly sell besides weight-loss drugs?
Lilly’s Key Products list also includes Ebglyss, Inluriyo, Jaypirca, Kisunla, Omvoh, Mounjaro, Zepbound and Foundayo [3]. On June 9, 2026, the FDA approved Ebglyss (lebrikizumab-lbkz) for one maintenance dose every eight weeks in moderate-to-severe atopic dermatitis [3]. The European Commission approved Jaypirca (pirtobrutinib) as a monotherapy for adults with chronic lymphocytic leukemia across all lines of therapy [3]. Jardiance revenue outside the US included a $250 million sales-based milestone from the Boehringer Ingelheim collaboration [3].
Lilly is also testing its marketed drugs in combination: Phase 3b TOGETHER-PsO and TOGETHER-PsA reported 52-week data on Taltz plus Zepbound in psoriatic disease and obesity [4].
How should patients read pipeline news right now?
Retatrutide cannot legally be sold or marketed for human use anywhere, and the only legal access is through Lilly’s clinical trials [2][4][5]. Eloralintide and bimagrumab are investigational with no approvals of any kind [6][7]. No regulator has reviewed black-market products for contents, dose accuracy or sterility, and “research-use only” labeling does not make them safe [4].
The headline trial numbers come from supervised, randomized study populations with dose-escalation schedules and documented discontinuation rates built in [1][2]. They describe what happened on average under study conditions — not what any individual will experience outside them [1][2].
Sources
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026.
- Eli Lilly and Company. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026.
- Eli Lilly and Company. Lilly reports second-quarter 2026 financial results, raises full-year guidance, and highlights continued growth and pipeline progress.
- Eli Lilly and Company. Lilly calls on online platforms, payment companies and regulators to shut down the illegal retatrutide black market. August 12, 2026.
- The Indiana Lawyer. Lilly fighting black market for its next obesity drug.
- Eli Lilly and Company. Lilly’s selective amylin agonist, eloralintide, demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity or overweight. November 6, 2025.
- BioPharma Dive. Lilly stops trial of muscle-sparing obesity drug.
- Eli Lilly and Company. FDA approves Lilly’s Foundayo (orforglipron), the only GLP-1 pill for weight loss that can be taken any time of day without food or water restrictions. April 1, 2026.
- Fierce Pharma. Lilly’s obesity pill Foundayo ‘disappointed’ in Q2, as injectables continue to boom. August 5, 2026.
- US Securities and Exchange Commission. Eli Lilly and Company annual report (Form 10-K) for fiscal year 2025.
- Labiotech. Eli Lilly pipeline in 2026 fueled by the incretin franchise.
- BioSpace. Deal-hungry Lilly strikes up to $2.9B immuno play for Merida. August 31, 2026.
- 2 Minute Medicine. Lilly Strikes $1.3 Billion GPCR Drug Discovery Pact with Superluminal.
- Eli Lilly and Company. Lilly partners with NVIDIA to build the industry’s most powerful AI supercomputer, supercharging medicine discovery and delivery for patients. October 28, 2025.
- Eli Lilly and Company. Lilly selects Pennsylvania as home for its newest injectable medicine and device manufacturing facility. January 30, 2026.
- US Food and Drug Administration. FDA Approves First New Molecular Entity Under National Priority Voucher Program.
- ClinicalTrials.gov. A Study of Eloralintide (LY3841136) in Participants With Obesity, or Overweight Without Type 2 Diabetes. NCT07321886.
Frequently asked questions
When will retatrutide be approved and available in the US?
No approval date exists. Lilly is completing its CMC data package and plans to submit a BLA to the FDA in Q1 2027, with a clinical data package it says is complete for obesity, obstructive sleep apnea and knee osteoarthritis pain.
How much weight did people lose on retatrutide versus Zepbound?
In TRIUMPH-1, retatrutide 12 mg produced 28.3% (70.3 lbs) average weight loss at 80 weeks on the efficacy estimand, with 45.3% of participants losing at least 30% of body weight. Patients on Wegovy or Zepbound can lose up to about 20% of body weight, by comparison. These are supervised trial averages, not individual outcomes.
Is retatrutide safe to buy online or from a peptide seller?
No. Retatrutide cannot legally be sold for human use anywhere, and the FDA says it cannot be lawfully compounded and that "research-use only" products are of unknown quality and may be harmful. Australian authorities reported six liver toxicity cases in users, and a preprint linked black-market use to lower weight loss and more cardiovascular symptoms.
What side effects did retatrutide cause in the trials?
The most common events were gastrointestinal. Across retatrutide arms in TRIUMPH-1, nausea reached 42.4%, diarrhea 34.1%, constipation 26.1% and vomiting 25.3%, versus much lower placebo rates. Discontinuation for adverse events reached 11.3% at 12 mg versus 4.9% on placebo. Dysesthesia occurred in up to 12.5% and was mostly mild to moderate.
How is eloralintide different from a GLP-1 drug?
Eloralintide is a once-weekly selective amylin receptor agonist, a different mechanism from GLP-1 drugs, likely working through satiety and reduced calorie intake. In Phase 2 it produced up to 20.1% (47.0 lbs) average weight loss at 48 weeks on the efficacy estimand, with GI symptoms and fatigue that were similar to placebo at lower doses.
Is there a drug to prevent muscle loss on obesity medication?
Not yet — no muscle-preservation drug is approved for this use. Lilly's bimagrumab is in Phase 2; one trial was canceled in September 2025 for "strategic business reasons," while a second in non-diabetic obesity was still recruiting with results expected around April 2026. Regeneron, Biohaven, Scholar Rock and Veru have competing candidates.
What is Foundayo and how does it differ from Zepbound?
Foundayo (orforglipron) is a once-daily GLP-1 pill, unlike Zepbound's weekly injection, and it targets GLP-1 only, not GIP. It is used with diet and exercise in adults with obesity or overweight with weight-related problems, must not be combined with other GLP-1 receptor agonists, and carries a boxed warning about thyroid tumors including thyroid cancer.
Did retatrutide reduce heart attacks or strokes?
The evidence is inconclusive. In TRIUMPH-3, the in-study MACE-5 hazard ratio was 0.82 (95% CI 0.55–1.22) and MACE-3 was 1.12 (95% CI 0.64–1.96) — confidence intervals that include no effect, with fewer events than anticipated in both arms. The trial did show reductions in triglycerides, blood pressure and other risk factors.
This article summarizes FDA labeling, published research and company information current as of September 14, 2026. It is not medical advice and does not replace a conversation with your own healthcare provider. How we research and verify.