Details of failed studies cast pall on Novo Nordisk’s GLP-1 as Alzheimer’s treatment

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By Deena Beasley and Julie Steenhuysen

SAN DIEGO, Dec 3 (Reuters) – Details from two large trials of Novo Nordisk’s GLP-1 drug semaglutide showed it provided no cognitive benefit for people with early Alzheimer’s disease, researchers said at a medical meeting on Wednesday, dashing remaining hopes that the widely used medication could help such patients.

The Danish drugmaker said last week that the trials, which were designed to show that its semaglutide pill Rybelsus could slow progression of the brain-wasting disease by at least 20%, did not meet their goals. 

The joint studies showed some improvement in a few biological measures of the disease, but most of the changes were small and not enough to make a difference in delaying cognitive decline.

Trial patients on Rybelsus did show significant suppression of a key marker of inflammation, but “we did not have the corresponding benefit on cognition that we had hoped for,” said Dr. Jeff Cummings, director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Nevada Las Vegas and the trials’ lead investigator.

Both trials showed that Rybelsus had no impact at all on the rate of decline in a clinical dementia score compared to a placebo after two years, according to results presented at the Clinical Trials in Alzheimer’s Disease meeting in San Diego.

“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 a key investigator on the studies.

Alzheimer’s, which gradually destroys memory and thinking skills, is characterized by changes in the brain, including the buildup of amyloid beta plaques and tau tangles that result in loss of neurons responsible for transmitting information.

“I hate to say it’s dead, but it’s hard to see what a feasible likely next step would be for amyloid-positive Alzheimer’s disease,” said Dr. Suzanne Craft, professor of gerontology and geriatric medicine at Wake Forest University School of Medicine. “There was a lot of hope that this would work.”

Craft was not involved in the studies.

Novo’s trials, which involved 3,800 participants with confirmed Alzheimer’s, did show that Rybelsus led to reductions of up to 10% in some Alzheimer’s biomarkers, including several measures of tau. 

“We know that amyloid removal needs to be much more rigorous before we see an effect,” Sano said. 

The two drugs currently approved for slowing Alzheimer’s, Eli Lilly’s Kisunla and Leqembi from Eisai and Biogen, work by removing those amyloid deposits and were shown in trials to delay disease progression by around 30%.     

Novo said the safety profile of Rybelsus was consistent with the daily pill’s approved use as a diabetes treatment. Semaglutide, also sold as a weekly injection as Ozempic for diabetes and Wegovy for weight loss, is associated with side effects such as nausea. 

‘STONE COLD NEGATIVE’ RESULTS

Much of the evidence suggesting a cognitive benefit from GLP-1s came from large population studies of people with diabetes. Novo suggested, however, that those studies had “biases,” and may have overstated the drug’s impact.

Peter Johannsen, Novo’s international medical vice president, on Tuesday said diabetes patients prescribed GLP-1s likely had access to endocrinologists, rather than only primary care, and may be in higher socioeconomic groups than the general population. 

Neurologists said more information is needed about the value of GLP-1s for brain diseases. “Would I do another Alzheimer’s disease trial? Probably not,” said Mayo Clinic Alzheimer’s expert Ronald Petersen. “These were so stone-cold negative, you would be hard-pressed to do another Alzheimer’s-specific trial.”

Petersen said it might still be worth doing a broader trial in people with dementia who have cognitive problems related to vascular disease, such as uncontrolled hypertension.

A Novo spokesperson said the company plans to discontinue both trials and is reviewing all data from the studies, adding that “it is too early to speculate” about whether the company will plan further research in Alzheimer’s disease. 

Full results of the Rybelsus trials will be presented at the 2026 Alzheimer’s and Parkinson’s Diseases Conferences in March.

(Reporting By Deena Beasley in San Diego and Julie Steenhuysen in Chicago; Editing by Bill Berkrot and Lincoln Feast.)