Eli LillyTwo star weight loss pillsThe "one-on-one" battle has spread to the field of oral drugs, and the pressure has been put on Novo Nordisk..
On September 17, Eli Lilly announced positive top-line results from the Phase III ACHIEVE-3 study. The 52-week study compared orforglipron (12 mg and 36 mg) with oral semaglutide (7 mg and 14 mg) in terms of glycemic control and weight loss across four active treatment groups. At 52 weeks, orforglipron achieved its primary endpoint and all key secondary endpoints across all dose groups, demonstrating superiority over oral semaglutide in terms of improvements in glycated hemoglobin (A1C) and weight.
Orforglipron is an oral small molecule GLP-1 receptor agonist from Eli Lilly , and Rybelsus is an oral GLP-1 drug from Novo Nordisk . The aforementioned study was a head-to-head comparison. A head-to-head study can be considered a direct comparison of the two drugs' efficacy and safety. According to Eli Lilly, in this oral drug comparison, it emerged victorious.
Specifically, in the ACHIEVE-3 study, orforglipron achieved its primary endpoint of superiority compared to oral semaglutide. Using target efficacy estimates, at week 52, orforglipron achieved mean A1C reductions of 1.9% in the 12 mg group and 2.2% in the 36 mg group, compared to 1.1% in the 7 mg group and 1.4% in the 14 mg group. In a secondary endpoint, 37.1% of participants receiving the highest dose of orforglipron achieved an A1C <5.7%, compared to 12.5% of participants receiving the highest dose of oral semaglutide. Regarding the key secondary endpoint of weight loss, participants receiving orforglipron achieved a mean weight loss of 6.6 kg (6.7%) in the 12 mg group and 8.9 kg (9.2%) in the 36 mg group, while those receiving oral semaglutide lost 3.6 kg (3.7%) in the 7 mg group and 5.0 kg (5.3%) in the 14 mg group.
Lilly also noted that at the highest dose, orforglipron achieved a 73.6% relative weight loss advantage over oral semaglutide. Furthermore, orforglipron demonstrated clinically meaningful improvements in several key cardiovascular risk factors, including non-HDL cholesterol, systolic blood pressure, and triglycerides.
In addition to this oral GLP-1 drug, Eli Lilly's dual-target GIP/GLP-1 receptor agonist, tilpotide, has also been tested head-to-head against semaglutide, with Eli Lilly claiming victory. For example, in a post-hoc analysis of the SURMOUNT-5 study, the effects of tilpotide and semaglutide on the predicted 10-year CVD risk over a 72-week period were evaluated in participants without a baseline history of cardiovascular disease (CVD). Results showed a 23.72% risk reduction in the tilpotide group, significantly superior to the 13.56% risk reduction in the semaglutide group.
Semaglutide, Novo Nordisk 's flagship product, generated approximately $16.5 billion in global revenue in the first half of the year, making it the world's top drug. Sales of the weight-loss version of semaglutide injection reached approximately $5.4 billion, a year-on-year increase of 78%. Semaglutide's closest competitor is Eli Lilly's telotriol, which generated $14.7 billion in global revenue in the first half of the year. Zepbound, the weight-loss version of telotriol, generated $3.381 billion, a year-on-year increase of 172%.
Faced with Eli Lilly's strong offensive on sales and research data for Tilpotide, Novo Nordisk is also not idle.
On September 1, Novo Nordisk released real-world data from the STEER study. The results showed that, compared with tilpotide, the weight-loss version of semaglutide reduced the risk of heart attack, stroke, cardiovascular-related death, and all-cause mortality by 57% in overweight or obese patients with cardiovascular disease, provided treatment was interrupted for no more than 30 days. During the trial, 15 (0.1%) cardiovascular events were recorded in the weight-loss semaglutide group and 39 (0.4%) in the tilpotide group.

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