Eli Lilly’s Oral GLP-1, Orforglipron, Demonstrates Efficacy and Safety Consistent with Injectable GLP-1s in Phase III Trial
In addition to meeting the primary endpoint of superior A1C reduction, the once-daily oral pill reduced weight by an average of 16 lbs.
Eli Lilly has shared positive Phase III clinical trial data of its investigational, oral glucagon-like peptide-1 (GLP-1), orforglipron in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. In the ACHIEVE-1 study evaluating orforglipron compared to placebo, the oral GLP-1 lowered A1C by an average of 1.3% to 1.6% across doses and reduced weight by an average 16 lbs. (7.9%) at the highest dose.1
These encouraging outcomes from ACHIEVE-1 were achieved at the 40-week mark. The trial met its primary endpoint of superior A1C reduction compared to placebo. In addition to the reduction in weight observed, another key secondary endpoint was met with 65% of participants taking the highest dose of orforglipron achieving an A1C less than or equal to 6.5%, which falls below the American Diabetes Association's (ADA) defined threshold for diabetes.
In a press release, David A. Ricks, Lilly chair and CEO, said: "ACHIEVE-1 is the first of seven Phase III studies examining the safety and efficacy of orforglipron across people with diabetes and obesity. We are pleased to see that our latest incretin medicine meets our expectations for safety and tolerability, glucose control and weight loss, and we look forward to additional data readouts later this year. As a convenient once-daily pill, orforglipron may provide a new option and, if approved, could be readily manufactured and launched at scale for use by people around the world."
The safety profile of orforglipron in ACHIEVE-1 was consistent with the established GLP-1 class. The most common adverse events for participants treated with the investigational therapy were diarrhea, nausea, dyspepsia, constipation, and vomiting.
The ACHIEVE-1 trial (NCT05971940) is a 40-week, randomized, double-blind, placebo-controlled study evaluating orforglipron at doses of 3 mg, 12 mg, and 36 mg as monotherapy. Across the US, China, India, Japan, and Mexico, the trial randomized 559 participants with the objective of demonstrating that orforglipron is superior in A1C reduction from baseline after 40 weeks, compared to placebo, in patients with type 2 diabetes who have not taken any anti-diabetic medications for at least 90 days prior to their first visit, and are naïve to insulin therapy.
Lilly’s Phase III ACHIEVE program has enrolled over 6,000 people with type 2 diabetes across five global registrational trials. The program started in 2023 and is expected to continue into 2026 with more results on the way.
Orforglipron was discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018. In addition to its exploration in weight management, the oral GLP-1 is being studied as a potential treatment for obstructive sleep apnea and hypertension in adults with obesity.
Reference
1. Lilly's oral GLP-1, orforglipron, demonstrated statistically significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful Phase 3 trial. News release. Eli Lilly. April 17, 2025. Accessed April 17, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-statistically
Improving Relationships and Diversifying the Site Selection Process
April 17th 2025In this episode of the Applied Clinical Trials Podcast, Liz Beatty, co-founder and chief strategy officer, Inato, discusses a number of topics around site engagement including community-based sites, the role of technology in improving site/sponsor relationships, how increased operational costs are impacting the industry, and more.
FDA-Approved Gene Therapy Beqvez Shows Sustained Efficacy, Safety in Long-Term Hemophilia B Trial
April 17th 2025Beqvez (fidanacogene elaparvovec), an FDA-approved one-time gene therapy for hemophilia B, demonstrated sustained factor IX expression, low bleeding rates, and a favorable safety profile over long-term follow-up.
Behind the Buzz: Why Clinical Research Leaders Flock to SCOPE Summit
February 7th 2025In this episode, we meet with Micah Lieberman, Executive Conference Director for SCOPE Summit (Summit for Clinical Ops Executives) at Cambridge Innovation Institute. We will dive deep into the critical role of collaboration within the clinical research ecosystem. How do we bring together diverse stakeholders—sponsors, CROs, clinical trial tech innovators, suppliers, patients, sites, advocacy organizations, investors, and non-profits—to share best practices in trial design, program planning, innovation, and clinical operations? We’ll explore why it’s vital for thought leaders to step beyond their own organizations and learn from others, exchanging ideas that drive advancements in clinical research. Additionally, we’ll discuss the pivotal role of scientific conferences like SCOPE Summit in fostering these essential connections and collaborations, helping shape the future of clinical trials. Join us as we uncover how collective wisdom and cross-industry partnerships are transforming the landscape of clinical research.
