Lilly's Oral GLP-1 Orforglipron Shows Promise in Phase 3 Obesity and Diabetes Trial

Eli Lilly has unveiled positive results from its phase 3 Attain-2 trial, evaluating the efficacy and safety of orforglipron, an oral GLP-1 receptor agonist, in patients with obesity or overweight and Type 2 diabetes. The study met its primary endpoint and all key secondary endpoints, demonstrating significant weight loss and improvements in glycemic control.

Impressive Weight Loss Results

Orforglipron, administered once daily without food or water restrictions, showed dose-dependent efficacy:

• The 36 mg dose led to an average weight reduction of 10.5% (22.9 pounds)
• The 12 mg dose resulted in a 7.8% (17.4 pounds) weight loss
• The 6 mg dose achieved a 5.5% (12.1 pounds) reduction

In comparison, patients on placebo experienced a modest 2.2% (5.1 pounds) weight decrease. Notably, over 50% of patients on the highest dose lost at least 10% of their body weight, with 28% achieving a 15% or greater reduction.

Glycemic Control and Cardiovascular Benefits

Beyond weight loss, orforglipron demonstrated significant improvements in glycemic control:

• The 36 mg dose lowered average A1C levels by 1.8% from a baseline of 8.1% after 72 weeks

The drug also showed promising effects on cardiovascular risk factors, including reductions in non-HDL cholesterol, systolic blood pressure, and triglycerides.

Safety Profile and Next Steps

Orforglipron's safety profile was consistent with previous clinical trials, with gastrointestinal side effects being the most common. These were generally mild to moderate in severity.

Kenneth Custer, Ph.D., Executive Vice President and President of Lilly's cardiometabolic health unit, emphasized the potential of orforglipron as a once-daily oral medication, stating that the results are "consistent with similar landmark trials for injectable GLP-1s."

With this positive data in hand, Lilly is moving swiftly towards global regulatory submissions, aiming to file before the end of the year. The company is also exploring orforglipron's potential as a maintenance therapy to prevent weight regain in patients who have had success with injectable obesity drugs like Zepbound.

As the pharmaceutical industry continues to advance in the treatment of obesity and diabetes, Lilly's orforglipron represents a significant step forward in the development of oral GLP-1 receptor agonists, potentially offering patients a more convenient alternative to injectable therapies.