Widely used drugs for diabetes and obesity, known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs), may play a role in improving survival rates among people with severe psychiatric disorders, according to a recent editorial published in the journal Expert Opinion on Pharmacotherapy.
The editorial suggests that GLP-1 RAs could help address the longstanding mortality gap faced by individuals with serious mental illnesses such as bipolar disorder, schizophrenia, and major depressive disorder. The authors state that these medications are most likely to improve outcomes by targeting cardiometabolic risk factors rather than replacing established psychiatric treatments.
"Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have potential to transform health outcomes for persons with bipolar disorder, schizophrenia, major depressive disorder and other serious mental illnesses by lengthening healthspan and reducing excess and premature mortality," the editorial notes.
GLP-1 RAs were first approved in 2005 by the U.S. Food and Drug Administration for treating type 2 diabetes. Since then, additional single-agent GLP-1 drugs have become available, along with dual-action agents like tirzepatide. Newer dual and triple agonists targeting multiple receptors are also in late-stage development.
These medications are now approved not only for diabetes but also for weight management in those who are overweight or obese, metabolic dysfunction-associated steatohepatitis with moderate or advanced fibrosis, obstructive sleep apnea in obese adults, reduction of cardiovascular events in adults with type 2 diabetes and cardiovascular disease, and slowing progression of chronic kidney disease alongside cardiovascular mortality.
Oral versions of synthetic small-molecule GLP-1 receptor agonists are expected to be approved by 2026. Oral semaglutide is already available on the market. These new formulations may make it easier for patients to access treatment due to simplified manufacturing and supply chains.
Experts widely agree that GLP-1 RAs have changed how type 2 diabetes and obesity are managed. They have been linked to lower rates of kidney disease progression, reduced cardiovascular disease risk, and decreased mortality among people living with metabolic disorders.
Serious mental illnesses such as schizophrenia, major depressive disorder, and bipolar disorder contribute significantly to disability and early death—often resulting in five to twenty-five years of life lost compared to the general population. Much of this excess mortality is attributed to higher rates of cardiovascular disease among these groups.
Current treatments like antipsychotics or lithium can be effective against psychiatric symptoms but have had limited impact on closing this mortality gap except for certain agents such as second-generation long-acting antipsychotics or clozapine. Lithium remains underused despite its proven benefits for bipolar disorder.
GLP-1 receptor agonists are recommended when managing weight gain caused by psychotropic drugs if stopping those medications is not possible. There is preliminary evidence suggesting they might protect against lithium-induced kidney damage—a condition currently lacking approved therapies—and some agents are being explored as treatments for substance use disorders involving alcohol, tobacco, or opioids.
Research from animal studies through small clinical trials has also indicated potential benefits from GLP-1 RAs in preventing mood disorders or addressing symptoms like cognitive impairment or loss of pleasure (anhedonia).
However, there are safety considerations: constipation from GLP-1 drugs may worsen gastrointestinal issues related to psychotropic medications; risks such as pancreatitis or muscle loss (sarcopenia) need monitoring; certain agents cannot be used by patients with severe kidney disease; ongoing surveillance is advised regarding suicide risk even though large studies do not show a direct link so far.
Despite decades of advances in psychiatric medication development,people living with serious mental illness continue to face much higher rates of early death, mainly due to physical health conditions like heart disease rather than their psychiatric diagnoses alone.
The editorial concludes: "Therapeutic strategies that directly reduce mortality and extend healthspan are therefore urgently needed." It highlights that "GLP-1 receptor agonists represent one of the most promising pharmacological classes," provided challenges around cost, access equity, reimbursement policies, and supply constraints can be resolved. Prioritizing individuals with severe mental illness within healthcare allocation frameworks could help reduce premature deaths among this vulnerable group soon.
