Lilly’s Oral GLP-1 Candidate Demonstrates 27-Pound Average Weight Loss in Phase III Trial

Eli Lilly and Company is reporting clinically meaningful weight loss data from a Phase III trial (ATTAIN-1) of orforglipron, its investigational oral glucagon-like peptide-1 (GLP-1) receptor agonist (1). In the study of more than 3000 adults with obesity, or who were overweight with a weight-related medical problem and without diabetes, Lilly said the primary endpoint was met with an average weight loss of 12.4%, or 27.3 pounds, versus 0.9% (2.2 pounds) with placebo.

Doses increased stepwise and randomized

The ATTAIN-1 trial enrolled adults classified as obese (with a body mass index [BMI] of 30 and above), or overweight (BMI 27 and above) without diabetes but with certain comorbidities: hypertension, dyslipidemia, obstructive sleep apnea (OSA), or cardiovascular disease. Orforglipron was administered in the trial at an initial dose of 1mg daily, then increased in a stepwise manner, at four-week intervals, to one of three randomized maintenance doses: 6mg, 12mg, or 36mg (1).

Patients enrolled in the study hail from the United States, Brazil, China, India, Japan, South Korea, Puerto Rico, Slovakia, Spain, and Taiwan.

"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," Kenneth Custer, PhD, executive vice-president and president of Lilly Cardiometabolic Health, said in a press release (1). "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. 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."

GLP-1 popularity peaking in 2025

The ubiquity of Novo Nordisk’s Ozempic and its prescription—albeit potentially to the point of misuse—in the past several years has placed a spotlight on the potential benefits of GLP-1s. In January 2025, FDA expanded the indications for Ozempic to include treatment for the reduction of risk of kidney disease worsening, kidney failure or end-stage kidney disease, and death due to cardiovascular disease in adults with type 2 diabetes and chronic kidney disease (2).

But even as GLP-1s were being touted as one of the pharmaceutical industry trends to watch for in 2025, drug developers were already looking beyond GLP-1s for the next generation of anti-obesity medicines.

Pharmaceutical Technology® Group’s “Behind the Headlines” and “Industry Outlook” series have both covered the GLP-1 market in-depth with the following interviews:

Behind the Headlines

• Episode 11–GLP-1 Patent Expiry, Recent Acquisitions, and Indirect Costs Capping
• Episode 14–Investment Trends, Policy Realignments, and Vaccines

Industry Outlook 2025

• Cell Therapy Advancement
• Evolving Pipelines and Supply Chain
• Through the Lens of a Service Provider

Meanwhile, in February 2025, Axplora announced a €50 million (US$58.1 million) investment to upgrade its Mourenx, France site’s infrastructure and capabilities related to peptide purification in a biologics environment, also looking toward development of next-generation therapeutics, specifically GLP-1s (3). In March, an agreement was reached for CordenPharma to provide its development and manufacturing services to help meet clinical and commercial demand of Viking Therapeutics’ GLP-1 candidate (4).

Detailed results from the ATTAIN-1 trial will be presented at the European Association for the Study of Diabetes Annual Meeting in September 2025, as orforglipron is not only under examination for weight management purposes; Lilly is also running Phase III trials to test its efficacy in treating type 2 diabetes, and it is being studied as a potential treatment for adults with obesity who have OSA or hypertension (1).

References

1. Eli Lilly and Company. Lilly's Oral GLP-1, Orforglipron, Delivers Weight Loss of Up to An Average of 27.3 Lbs. in First of Two Pivotal Phase III Trials in Adults with Obesity. Press Release. Aug. 7, 2025.
2. Novo Nordisk. FDA Approves Ozempic (semaglutide) as the Only GLP-1 RA to Reduce the Risk of Worsening Kidney Disease and Cardiovascular Death in Adults with Type 2 Diabetes and Chronic Kidney Disease. Press Release. Jan. 28, 2025.
3. Axplora. Axplora Announces €50 Million Investment in GLP-1 Manufacturing at Mourenx (France) Site. Press Release. Feb. 12, 2025.
4. CordenPharma. CordenPharma & Viking Therapeutics Sign Long-Term Strategic Partnership for Integrated Supply of GLP-1 Peptides, Injectables & Oral Formulations. Press Release. March 11, 2025.