Eli Lilly’s orforglipron claims a slight advantage over higher-dose oral semaglutide in weight loss and blood sugar reduction, signalling intensified competition in the race to develop effective oral GLP-1 therapies.
Eli Lilly says its oral diabetes pill orforglipron has shown a slight edge over Novo Nordisk’s higher-dose oral semaglutide in an indirect comparison of adults with type 2 diabetes, adding another data point to the increasingly crowded race to bring GLP-1 medicines into tablet form.
According to Lilly, the analysis found that orforglipron 17.2 mg produced 1.5 percentage points more weight loss and a 0.3 percentage point greater reduction in HbA1c, the measure used to track average blood sugar, than oral semaglutide 25 mg after 52 weeks. The company emphasised that the result came from cross-trial modelling, not a direct head-to-head trial, and therefore should be interpreted cautiously.
The comparison drew on two separate phase 3 studies published in The Lancet. ACHIEVE-3 tested orforglipron in 1,698 adults whose diabetes was not adequately controlled on metformin, while PIONEER PLUS evaluated higher doses of oral semaglutide in 1,606 participants. The studies were not identical: ACHIEVE-3 was open-label and enrolled people with a lower average starting HbA1c, while PIONEER PLUS was double-blind and included participants using one to three oral glucose-lowering medicines.
Lilly said the analysis adjusted for age, sex, baseline weight and baseline HbA1c, and that alternative statistical methods produced similar findings. Even so, the gap was modest and, as the company acknowledged, indirect comparisons can only go so far when trial designs and patient populations differ.
Rachel Batterham, Lilly’s senior vice president of medical innovation and external engagement at its cardiometabolic division, said in the company’s release: “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.” The result also highlights the sharper competition between Lilly and Novo Nordisk, both of which are trying to define the future of oral GLP-1 treatment before a direct comparison settles the question.
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