Novo Nordisk's Semaglutide Shows Mixed Results in Cardiovascular Trials

Novo Nordisk, a leading player in the diabetes and obesity treatment market, presented new data for its blockbuster GLP-1 therapy semaglutide at the 2025 Scientific Session and Expo of the American College of Cardiology. The results, while promising in some areas, paint a complex picture of the drug's cardiovascular benefits.

SOUL Trial Reveals Inconsistent Cardiovascular Outcomes

The Phase IIIb SOUL trial, focusing on patients with type 2 diabetes and cardiovascular disease and/or chronic kidney disease, demonstrated that oral semaglutide (Rybelsus) significantly reduced major adverse cardiovascular events (MACE) compared to placebo. However, analysts at BMO Capital Markets noted "inconsistent benefit" across different outcomes.

Full results published in the New England Journal of Medicine showed that Rybelsus' MACE benefit was primarily driven by a decrease in nonfatal myocardial infarction. Notably, the drug failed to significantly impact other MACE components, including cardiovascular death and nonfatal stroke.

Furthermore, Rybelsus did not show a significant benefit for major kidney disease events. This limitation prevented subsequent testing for death from cardiovascular causes and major adverse limb events, according to BMO analysts.

STRIDE Trial Demonstrates Promising Results for Ozempic

In contrast to the mixed results of the SOUL trial, Novo Nordisk reported more positive outcomes from the Phase IIIb STRIDE trial, which evaluated once-weekly Ozempic in patients with type 2 diabetes and peripheral artery disease.

The STRIDE trial showed that Ozempic improved maximum walking distance by 13% compared to placebo, with a mean treatment difference of 39.9 meters on a steep incline at 52 weeks. The drug also met key secondary endpoints, including improvements in pain-free walking distance and health-related quality of life.

Novo Nordisk characterized Ozempic's outcomes as "superior and clinically meaningful." BMO analysts concurred, suggesting that the STRIDE findings indicate "a broader anti-inflammatory impact of GLP-1 treatment that contributes to cardiovascular benefit."

Implications for Novo Nordisk's GLP-1 Franchise

Based on the results from both the SOUL and STRIDE trials, Novo Nordisk has filed for label expansions of Rybelsus and Ozempic, respectively. The FDA has accepted these filings, with decisions expected later this year.

However, the inconsistent benefits observed in the SOUL trial may pose challenges for Novo Nordisk's oral semaglutide position in the market. BMO analysts anticipate that next-generation assets like orforglipron could potentially challenge Novo's oral market share in the future.

As the pharmaceutical industry continues to evolve, these mixed results highlight the complexity of developing effective treatments for cardiometabolic conditions and underscore the importance of ongoing research in this field.