Although data for Eli Lilly’s orforglipron may have disappointed investors earlier this month, a new release of Phase III data in diabetic patients signals a positive turnaround for the oral glucagon-like peptide-1 receptor agonist (GLP-1RA) as the drugmaker accelerates regulatory activity.
The new data comes from the Phase III ATTAIN-2 trial (NCT05872620) evaluating orforglipron in adults who have obesity or are overweight and live with type 2 diabetes (T2D). All three doses of the therapy met primary and secondary endpoints.
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Share price in NYSE-listed Eli Lilly rose 2.8% to $716.24 at market open following the announcement on 26 August. Investor optimism continued throughout the day, with shares rising a further 2.7% to $736.03 by market close. The US big pharma company has a market cap of $659.8bn.
William Blair analyst Andy Hsieh said: “In another surprising development, orforglipron outperformed investor expectations in patients living with both overweight/obesity and T2D, which we view as the higher-risk and more difficult-to-treat population.”
Patients lost an average of 10.5% (22.9lb) of their weight when taking the highest dose of orforglipron (36mg) once per day without food or water restrictions for 72 weeks. The drug also reduced average blood sugar levels and cardiometabolic risk factors, reinforcing its wide-ranging benefits.
While all doses of orforglipron demonstrated robustness in weight loss, the degree of this decreased as doses were stepped down. Orforglipron 12mg reduced weight by 7.8%, and a 6mg dose cut weight by 5.5%, versus 2.2% in the placebo group.
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By GlobalDataExamining the secondary endpoints, more than half of the participants taking the 36mg dose lost at least 10% of their body weight, compared to 7% in the placebo group. For those who lost at least 15% of their body weight, this value dropped to 28.4%.
The oral drug’s safety aligns with its known profile from other clinical trials. The most common side effects in the study were gastrointestinal, which were generally mild to moderate in severity.
Eli Lilly will share full data from the study at a future medical meeting. The company confirmed it now has the “full data package” to advance with global regulatory submissions.
Lilly’s cardiometabolic health president Kenneth Custer said: “With these positive data in hand, we are moving with urgency toward global regulatory submissions to potentially meet the needs of patients who are waiting. If approved, we are ready to offer a convenient, once-daily pill that can be scaled globally.”
The results in diabetes patients mark a contrast to results from data reported from ATTAIN-1 (NCT05869903) earlier this month by Lilly. ATTAIN-1, which evaluated orforglipron in obese and overweight patients who did not have T2D, left investors underwhelmed. The oral medicine led to an average weight reduction of 12.4% (27.3 pounds) at the highest dose, comparing unfavourably to data from rival Novo Nordisk.
The ATTAIN-2 data might have gone some way therefore to rebuilding confidence in future market share.
Hsieh added: “Accounting for the three Phase III studies of orforglipron, we believe the franchise exhibited the highest competitive advantage in diabetes (roughly 15% of the US adult population).”
Novo Nordisk still ahead in regulatory race
Novo Nordisk will still likely beat Eli Lilly to market the next generation of oral GLP-1RA drugs, however. Earlier this year, the Danish drugmaker submitted a new drug application (NDA) to the US Food and Drug Administration (FDA) for its oral 25mg semaglutide. The treatment led to an average of 13.6% weight loss compared to 2.2% in the placebo cohort after 64 weeks in the OASIS4 trial (NCT05035095).
Novo Nordisk expects a decision from the FDA in Q4 2025 for its candidate, which will be marketed as Wegovy, the same brand name given to the subcutaneous version of the drug approved for weight loss. Oral semaglutide is already available on the market for patients with T2D in the form of Rybelsus, first approved in 2019. However, the maximum dose of this drug is far lower than that being evaluated in current studies with the next generation of oral weight loss drugs.
