Baqsimi was launched as an option to provide rescue treatment for diabetes patients who take insulin. Credit: Diabetesmagazijn.nl on Unsplash.
Eli Lilly’s Phase III trial with its oral weight loss pill, orforglipron, has met its primary endpoint, reducing A1C levels by up to 1.6%.
In the first of several readouts expected from a Phase III programme, Lilly said its
oral glucagon-like peptide-1 receptor agonist (GLP-1RA)
demonstrated significant efficacy while maintaining a safety profile consistent with subcutaneously delivered GLP-1RA drugs. Eli Lilly’s stock jumped up by 13.8% at market open today (17 April). The company has a market cap of $659.93bn.
This news comes just days after
Pfizer culled its second obesity pill due to a liver injury incident in a patient
. The manageable safety profile of Lilly’s drug marks an important development in the field of
oral GLP-1RAs
.
Based on this update and other trials from the programme that are due to read out later this year, Lilly expects to submit an approval application for orforglipron as a weight management treatment to global regulatory agencies by the end of this year, with the submission for the treatment of type 2 diabetes (T2D) anticipated in 2026.
If it gains market approval, GlobalData predicts sales of orforglipron to reach $11.8bn in 2030. The global GLP-1RA market is experiencing substantial growth and is projected to reach $125bn by 2033.
GlobalData
is the parent company of
Clinical Trials Arena
.
Efficacy and safety proven in first study
In the randomised, placebo-controlled, double-blind ACHIEVE-1 trial (NCT05971940), the efficacy and safety of three doses – 3mg, 12mg and 36mg – of orforglipron were evaluated in adults with T2D and inadequate glycemic control with diet and exercise alone.
The drug reduced A1C levels by an average of 1.3% to 1.6% from a baseline of 8.0% after 40 weeks. It also scored in a key secondary endpoint, with more than 65% of participants taking the highest dose of orforglipron achieving an A1C less than or equal to 6.5%, which is below the American Diabetes Association’s (ADA) defined threshold for diabetes.
Finally, there was significant weight loss achieved in the study, with patients losing an average of 16lb (7.9%) in the highest dose cohort. This weight loss had not plateaued, indicating potential further weight loss could be possible with further dosing. Meanwhile, the placebo cohort saw an average weight loss of 3.4lb.
In addition to the efficacy, Lilly has also touted that orforglipron’s safety profile in ACHIEVE-1 and said it was consistent with the established GLP-1RA class, with the most commonly reported adverse events (AEs) being gastrointestinal-related and generally mild to moderate in severity. No hepatic safety signal was observed.
Treatment discontinuation rates due to AEs were 6% in the low-dose group, 4% in the medium-dose cohort and 8% in the high-dose group compared to 1% with placebo.
A Bank of America Securities report said that the four main parameters for assessing orforglipron were weight loss, blood sugar control, tolerability and safety, describing the data for all these as “solid”. This data readout was viewed as a closely watched event, and all eyes are now on Novo Nordisk’s oral GLP-1RA drug Rybelsus, which is approved for T2D, but not for weight management. The report said Rybelsus is a peptide with certain limitations, while orforglipron, being a small-molecule drug, could be easy to scale and produce.
Eli Lilly’s CEO David Ricks said: “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. We look forward to additional data readouts later this year.”
Lilly states that orforglipron is the first oral small molecule GLP-1RA, taken without food and water restrictions, to successfully complete a Phase III trial. If approved, the company is confident in its ability to launch orforglipron worldwide without supply constraints, something that
until recently has plagued the GLP-1RA market
. Data is set to be presented at ADA’s 85th Scientific Sessions in June 2025 and published in a peer-reviewed journal.
Lilly already a powerhouse in the weight loss space
Eli Lilly has already cemented its name in the GLP-1RA space with its subcutaneous therapy, tirzepatide, which is marketed as Mounjaro for T2D and Zepbound for obesity. GlobalData predicts a global sales forecast for tirzepatide of $26.75bn in 2030.
Its main competitor in the space currently is Novo Nordisk, which is also a high flier with its GLP-1RA semaglutide, marketed as Ozempic for T2D and Wegovy for weight loss.
Other companies are trying to break into the space, including Viking Therapeutics, which is set to initiate trials of VK2735, with the subcutaneous formulation set to enter a Phase III trial in Q2 2025 and the oral version in an ongoing Phase II study (NCT06828055).
While Pfizer pulled its oral candidate, danuglipron, from development earlier this week, the company does have another obesity pill – PF-07976016, which is in a Phase IIa trial.
