Source – Eli Lilly
On June 23, 2023, Eli Lilly and Company announced the Phase II results for orforglipron, an oral nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist being investigated for chronic weight management in individuals with obesity or overweight. The data, presented at the American Diabetes Association’s 83rd Scientific Sessions and published in the New England Journal of Medicine, demonstrated significant weight reductions in adults with obesity or overweight and at least one weight-related comorbidity (excluding type 2 diabetes).
“We recognize that obesity is a global epidemic and there is a need for a variety of effective medications and administration routes. We are working to address these needs by researching different options, including a daily oral pill called orforglipron. In a Phase II study, orforglipron demonstrated an average of up to 14.7% weight reduction. These exciting results indicate that orforglipron may be an effective, once-daily oral that can be taken without food or water restrictions.”
– Dr. Sean Wharton, Director at Wharton Medical Clinic
All tested doses of orforglipron met the primary and secondary endpoints for efficacy estimand at 36 weeks of treatment. The key secondary endpoints achieved by participants included:
- Body weight reductions of ≥5%: 72% (12 mg), 90% (24 mg), 92% (36 mg), and 90% (45 mg) compared to 24% with placebo.
- Body weight reductions of ≥10%: 47% (12 mg), 62% (24 mg), 75% (36 mg), and 69% (45 mg) compared to 9% with placebo.
- BMI reduction from baseline: 3.4 kg/m2 (12 mg), 4.7 kg/m2 (24 mg), 5.0 kg/m2 (36 mg), and 5.5 kg/m2 (45 mg) compared to 0.9 kg/m2 with placebo.
- Waist circumference reduction from baseline: 9.6 cm (12 mg), 11.2 cm (24 mg), 10.6 cm (36 mg), and 13.6 cm (45 mg) compared to 4 cm with placebo.
Additionally, a separate Phase II study evaluated orforglipron for the treatment of type 2 diabetes compared to placebo and dulaglutide. The results, presented at the same scientific sessions and published in The Lancet, demonstrated meaningful reductions in A1C (a measure of blood sugar control) and body weight at 26 weeks. The adverse events profile of orforglipron was consistent with other GLP-1 receptor agonists.
At the 26-week primary endpoint, orforglipron showed statistically significant dose-dependent body weight reductions ranging from 8.6% to 12.6% compared to placebo. At 36 weeks, all doses of orforglipron achieved body weight reductions ranging from 9.4% to 14.7% compared to placebo. The mean baseline body weight of participants was 240 lb (109 kg).
The safety profile of orforglipron was similar to other drugs in the same class, with gastrointestinal side effects being the most commonly reported adverse events, typically occurring during the dose escalation period.
“People living with chronic diseases such as type 2 diabetes and obesity deserve options – including oral treatments – to meet their treatment needs. In two Phase II studies, orforglipron demonstrated the ability to lower weight and A1C in both patient populations. These study results support the continued development of orforglipron in Phase III. We look forward to those results and the continued development of our pipeline assets that explore novel treatments for type 2 diabetes and obesity.”
– Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly
Eli Lilly has initiated Phase III development programs (ATTAIN trials for obesity and overweight, ACHIEVE trials for type 2 diabetes) to further investigate the efficacy and safety of orforglipron.
