According to BMO Capital Markets, Rybelsus’ outcomes in SOUL were “inconsistent,” failing to significantly lower cardiovascular death and nonfatal stroke.
Novo Nordisk presented additional cardiovascular data this weekend for its blockbuster GLP-1 therapy semaglutide, touting the drug’s potential for addressing cardiometabolic conditions.
But analysts at BMO Capital Markets, writing in a weekend investor note, were not totally convinced, pointing to the “inconsistent benefit” of semaglutide for certain outcomes.”
The Phase IIIb SOUL trial focused on patients with type 2 diabetes and cardiovascular disease and/or chronic kidney disease. Full results, published in the New England Journal of Medicine, showed that most of oral semaglutide (Rybelsus’) major adverse cardiovascular events (MACE) benefit was driven by a decrease in nonfatal myocardial infarction.
Meanwhile, other MACE components, such as cardiovascular death and nonfatal stroke, were not significantly impacted by Rybelsus.
The data were presented at the 2025 Scientific Session and Expo of the American College of Cardiology.
As BMO stated, however, the benefits were inconsistent.
Results from the SOUL trial found that while Novo’s Rybelsus—an oral, 14-mg formulation of semaglutide—could indeed significantly reduce major adverse cardiovascular events (MACE) versus placebo, its effects on individual outcomes varied widely.
However, Rybelsus failed to show a significant benefit for major kidney disease events, which according to BMO, prevented subsequent testing for death from cardiovascular causes and major adverse limb events. These “inconsistent” findings could point to potential limitations in the benefits of using oral semaglutide, the analysts added.
“While oral [semaglutide] continues to show modest benefits in weight loss and secondary indications relative to injectables, we anticipate next generation assets like orforglipron could start to challenge Novo’s oral position share in the future,” they said.
Also at ACC 2025, Novo released detailed data from the Phase IIIb STRIDE trial of once-weekly Ozempic in patients with type 2 diabetes and peripheral artery disease. Results showed that Ozempic improved maximum walking distance by 13% versus placebo, while also eliciting a mean treatment difference of 39.9 meters on a steep incline at 52 weeks. The drug also hit key secondary endpoints, including pain-free walking distance and health-related quality of life.
Overall, Novo called Ozempic’s outcomes “superior and clinically meaningful.”
In this regard, the BMO analysts agreed, noting that “STRIDE’s findings also suggest “a broader anti-inflammatory impact of GLP-1 treatment that contributes to cardiovascular benefit.”
Based on data from SOUL and STRIDE, Novo has filed for the label expansion of Rybelsus and Ozempic, respectively. The FDA has accepted these filings, with decisions expected this year.
