GLP-1s may offer better dementia protection than metformin

Medical News Today

28-07-2025

There were about 589 million adults around the world living with diabetes in 2024, with 90% having type 2 diabetes. Past studies have shown that people who have type 2 diabetes are at a higher risk of developing dementia. A new study has found that when it comes to the neuroprotective abilities of diabetes medications, people taking GLP-1 agonists had a significantly lower cumulative risk of developing dementia, when compared to metformin users.The International Diabetes Federation reports there were about 589 million adults around the world living with diabetes in 2024, with 90% of these having type 2 diabetes. Past studies show that people who have type 2 diabetes — a chronic condition where the body does not use its insulin properly — are at a higher risk of developing dementia. 'Type 2 diabetes is not only a metabolic disorder but also a major risk factor for dementia, particularly Alzheimer's disease and other nonvascular dementias,' Szu-Yuan Wu, MD, MPH, PhD, professor of radiation oncology and pharmacoepidemiology at Asia University, and director of the Big Data Center at Lo-Hsu Medical Foundation at Lotung Poh-Ai Hospital, both in Taiwan, told Medical News Today.'The risk of developing dementia is approximately 1.7 times higher in individuals with type 2 diabetes than in the general population. This imposes significant burdens on families and healthcare systems,' Wu explained.He is first and co-senior author of a new study recently published in the journal BMJ Open Diabetes Research & Care.The study found that when comparing the neuroprotective abilities of two diabetes medications — metformin and glucagon-like peptide-1 receptor agonists (GLP-1 agonists) — participants taking GLP-1 agonists had a significantly lower cumulative risk of developing dementia, when compared to metformin. Comparing GLP-1s, metformin head-to-headFor this study, researchers analyzed electronic health record data from the global health research network TriNetX. Scientists focused on data from more than 87,000 people with an average age of 58 who had type 2 diabetes and were prescribed either metformin or a GLP-1 agonist, to track any dementia development. 'Although metformin is widely accepted as the first-line therapy for type 2 diabetes, its effects on cognitive outcomes have been inconsistent,' Wu said. 'We aimed to investigate whether starting with a second-line agent like GLP-1 agonists might confer greater protective effects against dementia.'No previous real-world study has directly compared GLP-1 agonists and metformin head-to-head for dementia prevention,' he continued. 'If GLP-1 agonists show superior neuroprotective benefits, this could challenge the traditional treatment paradigm and support initiating therapy with GLP-1 agonists in selected patients.''GLP-1 agonists have demonstrated mechanisms that include reducing neuroinflammation, enhancing cerebral glucose metabolism, and improving synaptic plasticity,' Wu added. 'Given these benefits, it is imperative that we continue exploring their broader therapeutic potential beyond glucose lowering.'GLP-1s lower Alzheimer's risk by 12% compared to metforminAt the study's conclusion, Wu and his team found that study participants taking GLP-1 agonists had a significantly lower cumulative risk of developing dementia — namely, 10% — with an incidence of about 2.5%.By comparison, the dementia incidence rate for those taking metformin was almost 5%. 'This nearly twofold difference in dementia incidence is clinically significant,' Wu explained.'It suggests that initiating treatment with GLP-1 agonists may be more effective than metformin in reducing dementia risk among individuals with type 2 diabetes. Given the high prevalence of both diabetes and dementia in aging populations, this strategy may reduce long-term public health burdens, including healthcare costs, caregiver stress, and institutionalization needs.'– Szu-Yuan Wu, MD, MPH, PhDThe researcher team also discovered that study participants taking GLP-1 agonists had a 25% lower risk of developing non-vascular dementias and a 12% lower chance of developing Alzheimer's disease, compared to participants taking metformin. 'These subtype-specific findings reinforce the mechanistic rationale for GLP-1 agonists in neuroprotection,' Wu said. 'They are known to reduce amyloid-beta accumulation, suppress tau hyperphosphorylation, improve cerebrovascular integrity, and lower systemic inflammation.''These effects are not only theoretical; clinical trials of agents like liraglutide have shown cognitive improvements in patients with early Alzheimer's disease. Our results support that these biological actions may translate into meaningful risk reduction in real-world populations,' he detailed.A novel, effective way of lowering dementia risk?MNT had the opportunity to speak with Michael Snyder, MD, FACS, FASMBS, medical director of the Bariatric Surgery Center at Rose Medical Center, founder and director of the Denver Center for Bariatric Surgery Foundation, and in-house obesity specialist for FuturHealth, about this study. Snyder, who was not involved in the research, commented that these findings are quite significant as an introduction to a novel and seemingly extremely effective way of decreasing the risk of type 2 diabetes related dementia, specifically, Alzheimer's disease and nonvascular dementia. 'Early research has suggested that GLP-1 medications may offer powerful benefits for brain health,' he explained. 'Obesity, insulin resistance, and type 2 diabetes are all known to increase the risk of dementia, largely due to their role in driving inflammation, vascular damage, and other long-term stressors on the brain. By targeting these underlying issues, GLP-1s, which are already widely used to treat obesity and diabetes, may offer indirect protection against cognitive diseases,' Snyder pointed out.'In addition, emerging evidence shows that GLP-1s may have direct neurological effects, influencing memory, cognitive function, and neuroinflammation,' he continued. 'Although promising, long-term studies and clinical trials are needed to fully understand GLP-1s impact on the brain. With that said, GLP-1s could play a pivotal role in preventing or slowing neurodegenerative diseases, marking a major step forward in the future of brain health.'More research needed for definitive conclusionsMNT also spoke to Jennifer Cheng, DO, chief of endocrinology at Hackensack Meridian Jersey Shore University Medical Center in New Jersey, about this research. 'As an endocrinologist who treats type 2 diabetes on a regular basis, I found the study to be thought provoking and an interesting avenue of research,' Cheng, who likewise was not involved in the research, commented. 'The cognitive complications of diabetes can be significant and life debilitating. The protective effect for diabetes is promising and may help with treatment decisions in the future. It is an interesting method of research and can lead to further discoveries.' 'We are discovering new effects of the GLP-1 medications and it is interesting to see the possible protective effects. Patients with diabetes do have increased risk for neurological disorders including vascular issues and dementia. This is just an observational study so there can be no conclusions about the medications being the definitive cause of the decreased risk of Alzheimer's and/or dementia.'– Jennifer Cheng, DO'For research next steps, it would be interesting to see the new GLP-1 medications, and effects of the GLP-1s, studied to see if it is definitive,' Cheng added. 'We cannot conclude that based on an observational study that the GLP-1 was the primary agent to help prevent the cognitive complications of diabetes, but it does warrant further investigation, especially with new GLP-1 medications in development.'