A transformative moment in the global fight against obesity has emerged with the announcement of positive topline results from Eli Lilly and Company’s Phase 3 ATTAIN-1 trial. This groundbreaking study evaluated orforglipron, an investigational once-daily oral glucagon-like peptide-1 (GLP-1) receptor agonist, presenting a potential paradigm shift in how weight management is approached worldwide.
On August 7, 2025, from Indianapolis, Eli Lilly shared that orforglipron demonstrated significant efficacy alongside a safety and tolerability profile consistent with existing injectable GLP-1 therapies. These compelling results were observed over a 72-week period, paving the way for a new era of accessible and convenient obesity care.
The ATTAIN-1 trial enrolled a substantial cohort of 3,127 adults across diverse global regions, including the U.S., Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain, and Taiwan. Participants included individuals with obesity or those classified as overweight with at least one weight-related medical problem, specifically excluding those with diabetes. The rigorous design of the trial involved a randomized, double-blind, placebo-controlled setup, ensuring robust data collection.
All three tested doses of orforglipron—6 mg, 12 mg, and 36 mg—successfully met the primary endpoint of superior body weight reduction when compared to placebo. Additionally, the investigational pill achieved all key secondary endpoints, further solidifying its potential. The trial specifically targeted individuals with a Body Mass Index (BMI) of 30.0 kg/m² or higher, or a BMI of 27.0 kg/m² or higher with a co-morbidity like hypertension, dyslipidemia, obstructive sleep apnea (OSA), or cardiovascular disease, coupled with a history of unsuccessful dietary weight loss efforts.
The most striking outcomes were seen with the highest dose of orforglipron. Using the efficacy estimand, which considers all randomized participants remaining on study intervention, the 36 mg once-daily dose led to an average weight reduction of 12.4%, equivalent to 27.3 pounds. This stands in stark contrast to the placebo group, which experienced only a 0.9% (2.2 pounds) average weight loss.
Delving deeper into the efficacy estimand results, the lower doses of orforglipron also showed meaningful reductions. The 6 mg dose resulted in an average weight loss of 7.8% (17.6 pounds), while the 12 mg dose yielded a 9.3% reduction (20.7 pounds). These figures underscore the dose-dependent efficacy of the oral therapy.
Beyond just weight loss, orforglipron demonstrated notable improvements in several known markers of cardiovascular risk. Pooled analyses across all doses revealed reductions in non-HDL cholesterol, triglycerides, and systolic blood pressure. In a pre-specified exploratory analysis, the highest 36 mg dose further reduced high-sensitivity C-reactive protein (hsCRP) levels by a significant 47.7%, indicating a potential positive impact on inflammation.
Examining the key secondary endpoints related to the percentage of participants achieving significant weight reductions, the highest dose of orforglipron showed impressive results. A remarkable 59.6% of participants taking the 36 mg dose achieved at least 10% body weight loss, while 39.6% lost at least 15% of their body weight. These figures compare favorably to the placebo group, where only 8.6% achieved a 10% reduction and 3.6% achieved a 15% reduction.
Product on Amazon: GLP-1 Supplement for Women and Men | Hunger & Metabolism Support – Expert Formulated to Support GLP1 Naturally | Probiotic and Prebiotic (60 Capsules)
Brand: Plus+Ultra
Binding: Product Group: Drugstore
Price: 24.99 USD
Rating: 4.0 Total reviews: 1031
Flavor: Unflavored
Unit Count: 60 Count
Item Form: Capsule
Product Benefits: Appetite Control & Suppressant, Weight Loss Support, Metabolism Support, Stomach Health
Number of Items: 1
Color: Beige
UPC: 850053558467
Manufacturer: Plus+Ultra
Shopping on Amazon >>
For the treatment-regimen estimand, which accounts for the estimated average treatment effect regardless of adherence to study intervention or initiation of prohibited weight management treatments, or forglipron also demonstrated statistically significant improvements across all primary and key secondary endpoints. With this estimand, the 36 mg dose led to an 11.2% (25.0 pounds) weight reduction, compared to a 2.1% (5.3 pounds) reduction in the placebo group.
The convenience of orforglipron is a significant differentiating factor. It can be taken once daily at any time without restrictions on food and water intake, offering a simple and flexible treatment regimen. Participants in the trial started with a 1 mg once-daily dose and gradually increased it in a step-wise approach at four-week intervals to their final randomized maintenance dose, with dose reduction allowed for gastrointestinal tolerability if other mitigations proved insufficient.
As with any medication, safety and tolerability are paramount considerations. The overall safety profile of orforglipron in ATTAIN-1 was found to be consistent with the established GLP-1 receptor agonist class. The most commonly reported adverse events were gastrointestinal-related, including nausea, constipation, diarrhea, vomiting, and dyspepsia.
Product on Amazon: musebeam GLP-1 Probiotic Weight Loss Support Supplement – Women Men GLP1 Booster with Berberine – Natural GLP 1 Support Appetite Suppressant Hunger Control Metabolism Fat Burn & Gut Health
Brand: musebeam
Binding: Product Group: Drugstore
Price: 29.99 USD
Rating: 4.1 Total reviews: 156
Flavor: Apple
Primary Supplement Type: GLP-1 Probiotic
Unit Count: 120 Count
Item Form: Capsule
Product Benefits: Weight Loss Support, Digestive Health Support, Metabolism Management
Age Range (Description): Adult
Package Information: Bottle
Number of Items: 1
Dosage Form: Gummy
Shopping on Amazon >>
These gastrointestinal side effects were generally mild to moderate in severity. For the 36 mg dose, nausea was reported by 33.7% of participants, constipation by 25.4%, diarrhea by 23.1%, vomiting by 24.0%, and dyspepsia by 14.1%. While these rates were higher than in the placebo group, they align with the known profile of this class of drugs.
Treatment discontinuation rates due to adverse events were 10.3% for the 36 mg orforglipron dose, compared to 2.6% for placebo. Overall treatment discontinuation rates for the 36 mg dose were 24.4%, notably lower than the 29.9% seen in the placebo group. Crucially, no hepatic safety signal was observed throughout the trial, addressing an important safety aspect.
Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health, articulated the profound significance of these findings. He stated, “Obesity is one of the most pressing global health challenges of our time, driving global chronic disease burden and impacting more than one billion people worldwide.” His words underscore the urgent public health need that orforglipron aims to address.
Dr. Custer emphasized the transformative potential of orforglipron, noting, “With orforglipron, we’re working to transform obesity care by introducing a potential once-daily oral therapy that could support early intervention and long-term disease management, while offering a convenient alternative to injectable treatments.” This highlights Lilly’s strategic vision for expanding access to effective weight management solutions.
He further added, “With these positive data in hand, we are now planning to submit orforglipron for regulatory review by year-end and are prepared for a global launch to address this urgent public health need.” This proactive stance from Lilly demonstrates their confidence in the drug’s profile and their commitment to rapid deployment.
Industry experts and physicians are keenly observing these developments. Dr. Céline Gounder, a medical contributor and editor-at-large for public health, described the pill as a “game changer” in terms of accessibility. She pointed out that injectables require needles and refrigeration, making pills considerably easier to manufacture and distribute, especially in regions with limited cold chain infrastructure.
Dr. Gounder anticipates that the pill will likely cost less than injectable treatments, a factor that could significantly broaden patient access. This potential for reduced cost, coupled with improved convenience, positions orforglipron as a vital tool in overcoming current limitations in obesity care.
Dr. David Cummings, an expert in obesity medicine at the University of Washington, concurred, suggesting that the ease of manufacturing pills could be their primary advantage. While acknowledging that the pill’s efficacy might not entirely match some injectable drugs, he posited that “that feature alone could make it truly impactful” if marketed at a considerably lower cost.
Product on Amazon: Allclair Nausea Relief Inhaler – Take Control of Motion Sickness, Morning Sickness, Medication, Stress – Fast, Natural, Drug-Free, Non-Drowsy & Portable Travel Essential – Pack of 2 Inhalers
Brand: Allclair
Binding: Health and Beauty Product Group: Drugstore
Price: 12.99 USD
Rating: 4.4 Total reviews: 1791
Special Feature: Non-Drowsy, Natural Ingredients, Fast-Acting
Item Weight: 0.3 Ounces
Product Benefits: Nausea Relief, Motion Sickness Relief
Specific Uses For Product: Morning Sickness, Nausea, Motion Sickness
Shopping on Amazon >>
Indeed, the current landscape of obesity treatment faces significant supply limitations. Dr. Custer noted that while approximately 170 million Americans could benefit from obesity drugs, only about eight million are currently taking them. This substantial gap is largely attributed to “production limitations” associated with injectable formulations, which are sterile solutions requiring cold storage and specialized pens or vials—a “capital-intensive” process.
In stark contrast, pills are far simpler to produce and can be manufactured at an “orders of magnitude differences” scale, according to Dr. Custer. This scalability is critical for meeting the immense unmet demand for obesity treatments globally, offering a practical solution for millions who currently lack access.
Several medical professionals lauded the results and the broader implications for patient care. Dr. Jaime Almandoz, medical director of the Weight Wellness Program at UT Southwestern Medical Center, described the outcome as “a strong and promising result for an oral agent,” calling the weight loss “a significant and clinically meaningful outcome.”
Dr. Almandoz acknowledged that “Injectables have set a high bar, but this study reinforces the potential for an oral GLP-1 to be transformative in obesity care, particularly for patients who are hesitant to start or maintain injectable therapies.” This perspective highlights the importance of offering diverse treatment options to cater to individual patient needs and preferences, such as a fear of needles.
Dr. Mihail “Misha” Zilbermint, director of Endocrine Hospitalists at Johns Hopkins Community Physicians, echoed this sentiment, believing the pill “has the potential to be a game changer, as long as people can tolerate the side effects.” This reiterates the balance between efficacy and real-world tolerability for widespread adoption.
Similarly, Dr. Amy Sheer, professor of medicine and program director of the Obesity Medicine Fellowship at the University of Florida, expressed hope that the pill would be less expensive than existing injections. She reasoned that lower prices could “help eliminate barriers to access for patients, potentially making insurers more willing to cover the drug.” This points to the crucial role of affordability in ensuring equitable access.
Comparing orforglipron to existing injectable GLP-1 drugs on the market, such as Novo Nordisk’s Wegovy and Eli Lilly’s own Zepbound and Mounjaro, provides a broader context. While orforglipron’s 12.4% average weight loss in the ATTAIN-1 trial compares favorably to Wegovy’s 13.2% over 72 weeks in its respective trial, it is somewhat less than Zepbound’s 20.2% weight loss seen in a separate study over the same duration.
Despite some analyst expectations for a 15% weight loss from orforglipron, Eli Lilly’s CEO, David Ricks, articulated the company’s satisfaction with the trial results. He stated, “We’re not disappointed with these results. It’s right on thesis for us.” He reaffirmed the company’s objective, saying, “The goal was to create an oral pill that was convenient and could be made at a huge scale, really, for the mass market, and had weight loss that was competitive with other single-acting GLP-1s, and that’s what we’ve achieved.”
Ricks added that the pill’s percentage of weight loss is “in the range” of what most people who are overweight or want to improve their metabolic health aim to achieve. This strategic perspective underscores Lilly’s focus on broad market accessibility and real-world applicability rather than solely aiming for the absolute highest weight loss percentages achieved by more complex injectable therapies.
Eli Lilly is making substantial investments to bolster its manufacturing capabilities, including building four new facilities in the U.S. through a $27 billion investment. These efforts are geared toward meeting the anticipated demand for orforglipron and other medicines upon launch, aiming to produce drugs for patients within the next five years. This foresight in production capacity is vital for ensuring widespread availability.
The ATTAIN-1 trial is just one component of Eli Lilly’s broader ATTAIN Phase 3 clinical trial program for orforglipron, which has enrolled over 4,500 individuals with obesity or overweight across two global registration trials. The program commenced in 2023, with additional results expected later this year. Furthermore, findings from the ACHIEVE Phase 3 clinical trial program, evaluating orforglipron for adults with type 2 diabetes, are also anticipated, expanding the potential indications for this versatile molecule.
Orforglipron, discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018, represents a significant scientific achievement. Its small molecule, non-peptide structure is key to its oral bioavailability, addressing a long-standing challenge in developing effective oral GLP-1 agonists that are not easily digested, unlike larger peptide molecules found in injectable versions.
The detailed ATTAIN-1 results are slated for presentation next month at the European Association for the Study of Diabetes (EASD) Annual Meeting 2025 and will subsequently be published in a peer-reviewed journal. This forthcoming detailed publication will allow the broader scientific and medical community to meticulously review the comprehensive data.
With these robust positive data in hand, Eli Lilly is confidently on track to submit forglipron to global regulatory agencies by the end of the year. This aggressive timeline suggests that the drug could potentially be available to consumers as early as 2026, marking a swift transition from trial success to patient access.
The prospect of a highly effective, once-daily oral GLP-1 therapy represents a monumental step forward in public health. It promises to democratize access to advanced weight management, moving beyond the current limitations of injectable treatments. Orforglipron stands as a testament to scientific ingenuity, poised to redefine the landscape of obesity care and offer renewed hope to millions grappling with this pervasive global health challenge, ushering in an era of broader reach and convenience.
