Orforglipron Shows Greater Weight Loss and HbA1c Reduction Than Oral Semaglutide in Indirect Comparison: Study
An indirect comparison of clinical trials in adults with type 2 diabetes found that Eli Lilly’s oral GLP-1 receptor agonist orforglipron (Foundayo) was associated with greater weight loss and a larger reduction in HbA1c levels than oral semaglutide (Rybelsus). The findings suggest potential differences in the efficacy of the two oral GLP-1 therapies in improving glycaemic control and body weight.
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
