Novo Nordisk Still Sees Potential for GLP-1 Drugs in Alzheimer’s Despite Major Trial Setbacks

By Blessing Nweke

Novo Nordisk says it remains optimistic that GLP-1 drugs could play a role in treating Alzheimer’s disease, even after two highly anticipated trials found no evidence that an older version of semaglutide slowed cognitive decline in people with early-stage disease.

The company’s evoke and evoke+ trials, discontinued last month, were widely viewed as a blow to one of the most closely watched experimental approaches for Alzheimer’s. GLP-1 drugs — best known for driving dramatic weight loss — have also been studied for their impact on inflammation, blood vessel health and metabolism in the brain, all factors believed to contribute to neurodegeneration.

“This is not what we hoped for,” said Dr. Peter Johannsen, Novo Nordisk’s international medical vice president of obesity and cardiometabolic. “We really did expect a change.”

At the Clinical Trials on Alzheimer’s Disease conference Wednesday in San Diego, Novo Nordisk presented Phase 3 findings showing that Rybelsus, an oral form of semaglutide for Type 2 diabetes, did not slow memory or thinking decline over two years in nearly 4,000 older adults with mild cognitive impairment or early Alzheimer’s.

Still, Johannsen noted promising biological signals. Biomarkers of inflammation and neurodegeneration were reduced by about 10% in participants taking the drug, though experts say benefits may require reductions closer to 20% or higher.

Some researchers argue trial design may have contributed to the disappointing outcome. Dr. Ronald Petersen of the Mayo Clinic said the oral drug delivers lower exposure than weekly injections, raising the possibility participants were underdosed. Others questioned whether standard cognitive measures — designed for amyloid-targeting drugs — can detect changes from metabolic treatments like GLP-1s.

Experts also suggested treatment may have begun too late. “These processes may help prevent early neurodegeneration but may not reverse disease once it is established,” said Dr. Paul Edison of Imperial College London.

Despite setbacks, scientists emphasize the research is far from over. “I don’t think it’s a nail in the coffin,” said Donna Wilcock of Indiana University.