Contrary to expectations that obesity drugs would help treat dementia as well as reduce weight, the actual clinical trials showed no meaningful effect.
Denmark-based drugmaker Novo Nordisk said on the 24th (local time) that two large clinical trials involving 3,808 people found no difference between semaglutide and a sham drug (placebo) in slowing the progression of Alzheimer's disease.
Semaglutide is a drug that mimics the glucagon-like peptide-1 (GLP-1) hormone. GLP-1 is a hormone secreted from the small intestine after meals that promotes the pancreas's secretion of insulin, which lowers blood sugar, and suppresses glucagon, which raises blood sugar. It was originally developed as Ozempic, a diabetes treatment that lowers blood sugar, and later evolved into the obesity injection Wegovy after its weight-loss effect was confirmed.
Alzheimer's disease is a degenerative brain disorder that accounts for two-thirds of dementia cases. Patients in the trial were 55 to 85 and had mild cognitive impairment or mild dementia due to Alzheimer's disease. Researchers randomly assigned them 1-to-1 to receive either a sham drug or an oral 14 mg dose of semaglutide once daily and observed them for 156 weeks. Novo Nordisk said semaglutide treatment led to improvements in Alzheimer's-related biomarkers, but this did not translate into a delay in disease progression.
Martin Holst Lange, chief scientific officer (CSO) and executive vice president for research and development at Novo Nordisk, said, "Given the significant unmet medical need in Alzheimer's treatment, we felt a responsibility to explore the potential of semaglutide despite the low likelihood of success," adding, "While semaglutide did not demonstrate efficacy in slowing the progression of Alzheimer's disease, it continues to provide benefits to individuals with type 2 diabetes, obesity, and related conditions."
The trial results have not yet been published in an international journal. Key findings will first be presented on Dec. 3 at the Clinical Trials on Alzheimer's Disease (CTAD) meeting in San Diego, and the full results are scheduled to be released in March next year at the International Conference on Alzheimer's and Parkinson's Diseases (AD/PD).
Earlier studies have repeatedly found that semaglutide is effective in suppressing various cancers and cardiovascular diseases. In clinical settings, there have been reports that semaglutide also helps prevent dementia. In April, a research team at the University of Florida said in JAMA Neurology that "semaglutide reduces dementia risk by 33% to 43%."
The researchers analyzed medical records of more than 390,000 patients aged 50 and older diagnosed with diabetes from January 2014 to June 2023, and said the group using semaglutide-based therapies had a 34% lower incidence of dementia, including Alzheimer's disease, than the group using blood sugar–lowering agents.
However, that study analyzed medical records to confirm that dementia occurred less often in the group taking obesity drugs; it was not a clinical trial like this one that randomly assigned patients to receive a placebo or an obesity drug and assessed treatment effects. Scientists noted that while GLP-1–class obesity drugs have shown results suggesting they can prevent neurodegenerative diseases, they are unlikely to help once the disease has progressed.
Susan Kohlhaas of Alzheimer's Research UK said the results would be a major blow to Alzheimer's patients and families. Kohlhaas said, "These trial results remind us once again that Alzheimer's disease is caused by several different biological processes," adding, "A single approach will not be enough."
Alzheimer's disease is known to occur when amyloid beta and tau proteins abnormally accumulate in the brain. Amyloid beta is originally a protein that protects nerve cells, but when it detaches from cells and forms clumps, it causes damage. Tau is also a protein that acts as a brace to maintain the structure of nerve cells, but when phosphate groups attach inside nerve cells and alter it, it becomes tangled clumps and causes problems in cognitive function.
References
Novo Nordisk, https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916462
JAMA Neurology (2025), DOI: https://doi.org/10.1001/jamaneurol.2025.0353