Eli Lilly reported an adjusted indirect comparison of Foundayo (orforglipron) versus oral semaglutide using pooled ACHIEVE-3 and PIONEER PLUS data presented at EASD. Over 52 weeks, Foundayo 17.2 mg produced an average 1.5% greater weight loss (95% CI: 0.2–2.7 percentage points) and a 0.3 percentage-point larger A1C reduction (95% CI: 0.1–0.6) than oral semaglutide 25 mg. Supplementary analyses supported these findings, though Lilly emphasises that head-to-head trials are needed for definitive comparison.
Foundayo Shows Greater Weight Loss and A1C Reduction Versus Oral Semaglutide in Indirect 52‑Week Analysis
Foundayo is currently approved in the US for adults with obesity. Credit: New Africa/Shutterstock.com.
Eli Lilly presented results from an adjusted indirect treatment comparison of its investigational oral GLP-1 receptor agonist Foundayo (orforglipron) against oral semaglutide at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan.
Key Findings
The pooled analysis used data from the ACHIEVE-3 and PIONEER PLUS trials and compared Foundayo 17.2 mg with oral semaglutide 25 mg over 52 weeks. After covariate adjustment for factors such as age, sex, baseline A1C and baseline weight, the analysis found:
- Greater weight loss: Foundayo produced an average 1.5% greater bodyweight reduction versus oral semaglutide (95% CI: 0.2 to 2.7 percentage points).
- Improved glycaemic control: Foundayo yielded an additional 0.3 percentage-point A1C reduction compared with oral semaglutide (95% CI: 0.1 to 0.6 percentage points).
Supplementary statistical approaches supported the same direction of effect, with observed weight-loss differences ranging from 1.5% to 2.4% and A1C differences of 0.3% to 0.6% favoring Foundayo.
Context and Limitations
These results come from an indirect comparison rather than a randomized head-to-head trial. Indirect methods can be useful when direct comparisons are not yet available, but they are subject to assumptions and potential confounding despite covariate adjustment. Lilly acknowledges that head-to-head trials remain the gold standard for comparing treatments.
Rachel Batterham, Senior Vice-President for Medical Innovation and External Engagement, Lilly Cardiometabolic Health, said that while head-to-head trials provide the best comparisons, indirect analyses can offer informative data points and that Foundayo's efficacy, combined with simpler dosing requirements, could make it a foundational option for adults with type 2 diabetes.
Regulatory Status and Development
Foundayo is a once-daily oral GLP-1 receptor agonist currently approved in the United States for adults with obesity or overweight with weight-related health conditions to support weight loss and maintenance alongside diet and exercise. The molecule was discovered by Chugai Pharmaceutical and licensed to Lilly in 2018. The ACHIEVE clinical programme for orforglipron has enrolled more than 6,000 adults with type 2 diabetes globally.
Separately, in June Lilly reported Phase III results from the BRUIN CLL-322 trial evaluating Jaypirca (pirtobrutinib) in combination with venetoclax and rituximab in relapsed or refractory CLL/SLL.
Bottom line: The adjusted indirect comparison suggests Foundayo may offer modestly greater weight loss and A1C reduction than oral semaglutide 25 mg over 52 weeks, but confirmatory head-to-head trials are needed to establish comparative effectiveness definitively.
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