Eli Lilly presented an indirect comparison using ACHIEVE-3 and PIONEER PLUS data showing Foundayo (orforglipron) 17.2 mg produced larger 52-week reductions in body weight and A1C than oral semaglutide 25 mg. The primary estimate showed a 1.5 percentage-point greater weight reduction (95% CI −2.7% to −0.2%) and a 0.3 percentage-point greater A1C drop (95% CI −0.6% to −0.1%) for Foundayo. Alternative analyses widened those advantages to 1.5–2.4 percentage points for weight and 0.3–0.6 percentage points for A1C. Because the comparison is indirect, a head-to-head randomized trial of these doses would be needed for definitive conclusions.
Lilly’s Foundayo (Orforglipron) 17.2 mg Shows Larger 52‑Week Weight and A1C Reductions Than Oral Semaglutide 25 mg in Indirect Analysis
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Eli Lilly reported results from an indirect treatment comparison indicating that Foundayo (orforglipron) 17.2 mg was associated with greater reductions in body weight and hemoglobin A1C than oral semaglutide 25 mg in adults with type 2 diabetes after 52 weeks. The analysis, presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan, pooled data from the ACHIEVE-3 and PIONEER PLUS clinical trials.
Key Findings
In the primary indirect comparison, patients receiving Foundayo 17.2 mg experienced an average 1.5 percentage-point greater reduction in body weight than those receiving oral semaglutide 25 mg (95% confidence interval [CI]: −2.7% to −0.2%). Foundayo was also associated with a 0.3 percentage-point greater reduction in hemoglobin A1C versus oral semaglutide 25 mg (95% CI: −0.6% to −0.1%). The analysis adjusted for sex, age, baseline A1C and baseline body weight.
Lilly also applied alternative statistical methods; those analyses produced weight-loss differences favoring Foundayo of 1.5 to 2.4 percentage points and A1C advantages of 0.3 to 0.6 percentage points versus oral semaglutide 25 mg.
Context and Limitations
These results come from an indirect treatment comparison rather than a randomized head-to-head trial between Foundayo 17.2 mg and oral semaglutide 25 mg, so they should be interpreted cautiously. The indirect approach synthesizes data across trials (ACHIEVE-3 and PIONEER PLUS) and adjusts for measured confounders, but it cannot fully replace evidence from a direct randomized comparison of the two specific doses.
For context, the ACHIEVE-3 head-to-head trial directly compared Foundayo (9 mg and 17.2 mg) with oral semaglutide (7 mg and 14 mg). In ACHIEVE-3, Foundayo 17.2 mg reduced A1C by 2.2% and produced average weight loss of 19.7 pounds, whereas patients taking oral semaglutide 14 mg showed an A1C reduction of 1.4% and average weight loss of 11.0 pounds. That direct comparison involved a lower semaglutide dose than the 25 mg dose evaluated indirectly here.
Regulatory And Development Notes
Lilly noted that the 25 mg dose of oral semaglutide is not currently approved in the United States for type 2 diabetes; Novo Nordisk has submitted an application to the U.S. Food and Drug Administration seeking approval for that higher dose. Foundayo (orforglipron) is currently approved by the FDA for weight management in adults with obesity or adults who are overweight with weight-related conditions and continues to be studied as a potential treatment for type 2 diabetes and other indications. Orforglipron was originally discovered by Chugai Pharmaceutical and licensed to Lilly in 2018.
Takeaway: The indirect analysis suggests a potential clinical advantage for Foundayo 17.2 mg over oral semaglutide 25 mg in 52-week weight and A1C outcomes, but definitive conclusions require direct randomized comparisons of these specific doses.
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