GLP-1s have shaken up treatment for weight loss with close to 1 in 5 Americans saying they have taken them at some point. Recently, experts shifted attention to the drugs’ effects on the brain. They include Diana Thiara, M.D., an internist and expert in obesity medicine who heads the UCSF Weight Management Program.
In her commentary, in JAMA Neurology, Thiara describes how animal studies have shown that GLP-1 may increase “synaptic plasticity,” the way the brain rewires its network to change how information is processed and stored. The drugs also show promise in reducing inflammation, free radicals, and damage to neurons, which are key factors in neurodegenerative diseases.
The next generation of GLP-1s, which is expected to be launched next year, may demonstrate amplified effects that could include improved neuroprotection, Thiara says, but its impact would need to be validated through rigorous clinical trials, she stated.
Protecting against dementia
Jeffrey Fessel, M.D., emeritus clinical professor of medicine at UCSF, believes that GLP-1s may be an antidote to dementia. In his literature review, he evaluated several human studies that looked at different types of GLP-1s and their effects on cognition.
What he found
One of the most promising studies he cited followed approximately 9,000 participants with Type 2 diabetes and cardiovascular risk. Those on the GLP-1 dulaglutide were found to have a 14% risk reduction of cognitive decline compared with those on placebo.
In a review study from Denmark, also analyzed by Fessel, dementia risk was lowered by 53% when patients with Type 2 diabetes on GLP-1s were compared to patients on placebo. However, only about 1 in 4 patients were over 70, and relatively few cases of dementia were identified among the participants. More modest results were found in a nationwide cohort of older Danish patients, who also had Type 2 diabetes. Those who took GLP-1s had an 11% reduced risk of dementia, compared to those who did not take the drug.
Other smaller studies that Fessel analyzed had mixed results. Overall, the studies showed that the drugs support vascular health, which may be especially helpful to those at risk of vascular dementia.
Why it matters
Vascular dementia is the second most common dementia, affecting 2.7 million Americans. GLP-1s reduce stroke risk, improve blood sugar, hypertension, and weight — conditions that directly contribute to vascular dementia.
GLP-1s may also reduce the risk of Alzheimer’s, the most common dementia affecting around 7 million Americans. However, this may derive from improvements to vascular and metabolic health, rather than its effects on amyloid and tau. Notably, a 2025 study showed that GLP-1s did not slow progression in patients with Alzheimer’s disease.
Can what helps with food addiction help with alcohol and drugs?
Three decades ago, pharmaceutical companies began promoting opioids as a treatment for chronic, non-cancer related pain. Soon, scores of Americans were hooked. A landmark 2025 study changed scientists’ understanding of addiction and may lead to a new treatment.
The study, led by UCSF neuroscientist Khaled Moussawi, M.D., Ph.D., looked at rats, which share remarkably similar brain-reward circuits as humans. Until then, scientists thought drug use and drug-specific cues triggered an excessive surge of dopamine, the so-called pleasure hormone, which drives craving, addiction and relapse.
What he found
In studying the behavior and dopamine neurons of rats that had been exposed to opioids, Moussawi and colleagues found that cues that were unrelated to drugs, but were encountered in the same context, were also implicated in addiction. These rats reacted to a sound that signaled sugar was on the way, in a similar manner to a different sound signaling opioids were on the way.
In the same way, humans with opioid use disorder have shown exaggerated craving responses to non-drug cues, like seeing certain people or feeling stressed — that may lead to relapse — as to drug cues, like seeing syringes and pills.
Shifting from rats to human clinical trials, Moussawi latest research focuses on the GLP-1 brenipatide, which is thought to target craving and drug use. Previous research has shown that earlier generation GLP-1s may mute the intensity of the dopamine surge that activates the “must-have” response when a drug cue is encountered. They may also prompt the brain to remain more neutral, by engaging its prefrontal cortex, which is responsible for impulse control and decision-making.
Since different addictions share overlapping brain circuitry, brenipatide may open treatment options for other substance use disorders, Moussawi thinks. He is the principal investigator of two trials* that test brenipatide’s effectiveness for alcohol use disorder and as an add-on therapy for opioid use disorder.
Why it matters
Some 28 million Americans have alcohol use disorder, and 2.7 million Americans have opioid use disorder. If approved, brenipatide will be the first drug to target core brain mechanisms that frequently trigger relapse.
