Orforglipron, an experimental oral GLP-1 receptor agonist intended for individuals with type 2 diabetes and obesity or overweight, reached a significant milestone with the announcement of encouraging topline findings from the Phase 3 ATTAIN-2 trial by Eli Lilly and Company. Lilly now has the complete clinical data package needed to initiate international regulatory submissions for what may be the first oral GLP-1 drug approved exclusively for the treatment of obesity, following the successful conclusion of this third Phase 3 study.
Primary Endpoint Success Delivers Meaningful Weight Loss
Orforglipron 36 mg demonstrated greater body weight reduction when compared to a placebo, helping the ATTAIN-2 trial accomplish its primary aim. Using the effectiveness estimand, participants who took the highest dose lost an average of 10.5% (22.9 pounds) of their baseline weight of 223.5 pounds at 72 weeks, whereas those who received a placebo lost only 2.2% (5.1 pounds).
Weight Loss Results Across All Doses:
- Dosage of 36 mg: 10.5% decrease (22.9 lbs lost),
- Dosage of 12 mg: 7.8% decrease (17.4 lbs lost),
- Dosage of 6 mg: 5.5% decrease (12.1 lbs lost),
- Placebo: 2.2% reduction (5.1 lbs lost).
Higher dosages of orforglipron result in larger weight loss advantages, according to the results, which clearly show a dose-response relationship. Notably, compared to just 7.0% and 1.9% with a placebo, 50.1% of people taking the highest dose experienced a clinically significant weight reduction of ≥10%, and 28.4% attained ≥15%.
The ATTAIN-2 results reinforce the potential for orforglipron, as a once-daily oral, to deliver meaningful weight loss and A1C reduction, consistent with similar landmark trials for injectable GLP-1s,
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 — removing barriers and redefining how obesity is treated around the world.
Kenneth Custer
Exceptional Glycemic Control Improvements
Orforglipron produced remarkable gains in glycemic control across all important secondary endpoints, in addition to weight management. At all doses, the drug reduced A1C from a baseline of 8.1% by 1.3% to 1.8%, with the largest reduction occurring at the highest dose.
Diabetes Management Outcomes
- 1.8% (36 mg), 1.6% (12 mg), and 1.3% (6 mg) A1C reductions compared to 0.1% (placebo)
- A1C <7% (the aim for managing diabetes) was attained by 85.1% of participants on the maximum dose.
- A1C ≤6.5% was attained by 75.0% of patients using 36 mg, fulfilling the American Diabetes Association’s criteria for diabetic remission.
- Just 10.6% and 23.0% of placebo participants met these goals, respectively.
Read More: Lilly’s Oral GLP-1 Orforglipron Shows Significant Weight Loss in Phase 3 ATTAIN-1 Trial
Comprehensive Cardiometabolic Benefits
In addition to glycemic control and weight loss, the experiment found other health advantages. Triglycerides, systolic blood pressure, and non-HDL cholesterol were among the major cardiovascular risk factors for which orforglipron showed clinically significant improvements in. The highest dose resulted in a 50.6% decrease in high-sensitivity C-reactive protein (hsCRP), a critical indicator of inflammation linked to the risk of cardiovascular disease, in a predetermined exploratory investigation.
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Treatment-Regimen Estimand Confirms Robust Efficacy
All major and important secondary endpoints showed statistically significant improvements, according to the treatment regimen estimand analysis, which takes rescue drugs and treatment discontinuations into consideration.
Weight Loss Results (Treatment-Regimen Estimation)
- 36 mg: 9.6% reduction (21.2 lbs),
- 12 mg: 7.0% reduction (15.9 lbs),
- 6 mg: 5.1% reduction (11.7 lbs),
- Placebo: 2.5% reduction (6.0 lbs).
Diabetes Control (Treatment-Regimen Estimation)
- A1C reductions: 1.7% (36 mg), 1.5% (12 mg), 1.2% (6 mg) vs. 0.5% (placebo),
- A1C <7% achievement: 75.5% (36 mg), 75.9% (12 mg), 64.6% (6 mg) vs. 30.5% (placebo).
Global Regulatory Approval
Lilly now has the complete clinical data set needed to start orforglipron’s worldwide regulatory submissions after ATTAIN-2 was completed. The business has stated that it intends to act quickly to satisfy the demands of patients who are on the waiting list. In the event that it is authorized, Lilly hopes to “offer a convenient, once-daily pill that can be scaled globally — removing barriers and redefining how obesity is treated around the world.”
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Graduated from the University of Kerala'20 with B.Sc. Botany & Biotechnology. Post-graduation in Biotechnology from the University of Kerala'22. Internship experience in Cancer Research.
