Weight-loss drugs linked to reduced risk of substance use disorders

The results of a new study add to the growing body of evidence supporting the potential use of weight-loss drugs in neuropsychiatric disorders 

A comprehensive cohort study has shed light on the benefits and risks associated with weight-loss drugs, offering valuable insights for clinical care and future research.

Published in Nature Medicine on 20 January 2024, the study found the use of glucagon-like peptide 1 receptor agonists (GLP-1RAs)—used to treat diabetes and obesity—associated with a reduced risk of substance use disorders (including alcohol, cannabis, opioid and stimulant use disorders).

Weight-loss drug use was also linked to decreased risks of psychotic disorders, seizures, neurocognitive disorders (including Alzheimer’s disease and dementia), coagulation disorders, cardiometabolic disorders, infectious illnesses and several respiratory conditions.

However, the use of GLP-1RAs was not without risks, as researchers identified an increased risk of gastrointestinal disorders, hypotension, syncope, arthritic conditions, nephrolithiasis, interstitial nephritis, and drug-induced pancreatitis associated with their use.

The analysis, utilising the U.S. Department of Veterans Affairs databases, compared 215,970 GLP-1 RA users with patients using sulphonylureas (n=159,465), DPP4 inhibitors (n=117,989), SGLT2 inhibitors (n=258,614), or a composite of the three (n=536,068).

Additionally, the study examined 1,203,097 individuals who continued the use of non-GLP-1RA antihyperglycemics as part of usual care.

Participants were enrolled between October 2017 and December 2023, with a median follow-up period of 3.7 years.

These findings build on previous evidence linking GLP-1RA use to a reduced risk of alcohol and tobacco use disorders.

“Overall, our results extended the body of evidence on the potential utility of GLP-1 RAs in neuropsychiatric disorders,” the researchers noted.

They emphasised the need to further evaluate the biology and effectiveness of GLP-1 RAs as “either a primary or adjuvant therapeutic” for use in the management of various substance use disorders, psychotic disorders and depressive disorders.

The research team, comprising Yan Xie, Taeyoung Choi, and Ziyad Al-Aly, conducted the study at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System, St. Louis, MO, USA.