Eli Lilly and Company (NYSE: LLY), the maker of Zepbound (tirzepatide) announced results from a new analysis showing that Foundayo (orforglipron) 17.2 mg was associated with significantly greater weight loss and better blood sugar control than oral semaglutide 25 mg in adults with type 2 diabetes. The findings are based on an indirect treatment comparison of Foundayo 17.2 mg against oral semaglutide 25 mg, drawing on data from ACHIEVE-3 and PIONEER PLUS.1,2,3,4 Presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, these results add to a growing body of evidence supporting Foundayo's efficacy.
"For someone managing type 2 diabetes, the choice between treatments is a decision that impacts their life every day," said Deborah Horn, D.O., director of the Center for Obesity Medicine at McGovern Medical School at UTHealth Houston. "Having data to help us compare available medications provides clinicians the opportunity to make informed treatment choices that fit each patient's needs."
In an indirect treatment comparison using data from ACHIEVE-3 and PIONEER PLUS, Foundayo 17.2 mg showed significantly greater weight loss and A1C reduction compared to oral semaglutide 25 mg at 52 weeks.5 On average, participants taking Foundayo 17.2 mg lost 1.5% more of their body weight compared to oral semaglutide 25 mg (95% CI -2.7%, -0.2%). Additionally, Foundayo lowered A1C by 0.3% more than oral semaglutide 25 mg (95% CI -0.6%, -0.1%). This analysis was covariate-adjusted for gender, age, baseline A1C and baseline weight. Analyses using different statistical methods produced consistent results, with Foundayo 17.2 mg showing 1.5% to 2.4% greater weight loss and 0.3% to 0.6% greater A1C reduction compared to oral semaglutide 25 mg.
"Head-to-head trials ultimately provide the best comparison of two medicines, but when we don't yet have those data, then other approaches can provide informative data points," said Rachel Batterham, OBE, MBBS, Ph.D., FRCP, senior vice president of medical innovation and external engagement, Lilly Cardiometabolic Health. "Results from this indirect treatment comparison suggest that Foundayo may deliver A1C and weight lowering that is similar to the 25 mg dose of oral semaglutide. These results, paired with simple administration free of fasting or water restrictions, are what make Foundayo a potentially foundational therapy for adults managing type 2 diabetes around the world."
About Foundayo (orforglipron)
Foundayo (orforglipron) is FDA-approved for adults with obesity, or some adults with overweight who also have weight-related medical problems, to reduce excess body weight and maintain weight reduction long term, alongside a reduced-calorie diet and increased physical activity. Foundayo is a once-daily small molecule (non-peptide) oral glucagon-like peptide-1 receptor agonist that can be taken any time of the day without restrictions on food and water intake. Orforglipron was discovered by Chugai Pharmaceutical Co., Ltd. and licensed by Lilly in 2018. Orforglipron is being studied as a potential treatment for type 2 diabetes, obstructive sleep apnea, osteoarthritis knee pain, hypertension, peripheral artery disease and stress urinary incontinence.
About ACHIEVE-3 and ACHIEVE clinical trial program
ACHIEVE-3 (NCT06045221) is a Phase 3, 52-week, randomized, open-label trial evaluating the efficacy and safety of orforglipron compared with oral semaglutide (Rybelsus) in adults with type 2 diabetes inadequately controlled with metformin. The trial randomized 1,698 participants across the U.S., Argentina, China, Japan, Mexico and Puerto Rico to receive either 9 mg or 17.2 mg orforglipron or 7 mg or 14 mg oral semaglutide in a 1:1:1:1 ratio. The primary objective of the study was to demonstrate that orforglipron is non-inferior in A1C reduction from baseline after 52 weeks compared with oral semaglutide when comparing the lower and higher doses.
In ACHIEVE-3, Foundayo lowered A1C by an average of 1.9% (9 mg) and 2.2% (17.2 mg) compared to 1.1% (7 mg) and 1.4% (14 mg) with oral semaglutide at 52 weeks. Foundayo also delivered greater weight loss, with participants losing an average of 14.6 lbs (6.7%; 9 mg) and 19.7 lbs (9.2%; 17.2 mg) compared to 7.9 lbs (3.7%; 7 mg) and 11.0 lbs (5.3%; 14 mg) with oral semaglutide.
The ACHIEVE Phase 3 global clinical development program for orforglipron enrolled more than 6,000 people with type 2 diabetes across five global registration trials.
