Key Points:
- Semaglutide showed no cognitive benefit in early Alzheimer’s trials.
- Modest biomarker improvements did not affect clinical outcomes.
- Novo Nordisk will discontinue the trials and assess future research options.
Novo Nordisk said Wednesday that two major Semaglutide Alzheimer trials show the drug provides no cognitive benefit for people with early Alzheimer’s, despite modest biomarker shifts and a consistent safety profile.
Trials Show No Cognitive Benefit
The trials tested the daily semaglutide pill Rybelsus in 3,800 participants with confirmed Alzheimer’s. Designed to show at least a 20 percent slowing in disease progression, the studies instead found no difference in two-year cognitive decline when compared with placebo.
“We did not have the corresponding benefit on cognition that we had hoped for,” said Dr. Jeff Cummings, lead investigator and director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada, Las Vegas.
Biomarker Signals Fail To Translate
Researchers reported reductions of up to 10 percent in several biomarkers, including measures of tau. But investigators said the changes were too small to influence clinical outcomes.
“I don’t see that it affects anything that is likely to affect Alzheimer’s disease,” said Dr. Mary Sano, a Mount Sinai Alzheimer’s researcher and key investigator on the studies.
Experts noted the Semaglutide Alzheimer findings narrow hopes for GLP-1 drugs in amyloid-positive Alzheimer’s, where other treatments that remove amyloid have shown roughly a 30 percent slowing in decline.
“I hate to say it’s dead, but it’s hard to see what a feasible next step would be,” said Dr. Suzanne Craft, a gerontology professor at Wake Forest University who was not involved in the trials.
Company Ends Studies, Reviews Next Steps
Novo Nordisk said the safety and tolerability of Rybelsus remain consistent with its approved use for diabetes. Side effects such as nausea matched prior results from semaglutide’s diabetes and weight-loss indications.
Much of the earlier optimism came from population studies in diabetes patients. Peter Johannsen, Novo’s international medical vice president, said those studies may have “biases,” including differences in access to specialist care.
Mayo Clinic neurologist Dr. Ronald Petersen called the results “stone cold negative” and said another Semaglutide Alzheimer trial is unlikely. He said the drug might still merit study in dementia linked to vascular disease, such as uncontrolled hypertension.
Novo said it will discontinue both Semaglutide Alzheimer trials and review all study data. The company said it is “too early to speculate” on future Alzheimer’s research plans. Full results will be presented at the Alzheimer’s and Parkinson’s Diseases Conferences in March 2026.
