Glucagon-like peptide-1 receptor agonists (GLP-1s, also known as incretin mimetics and GLP-1 analogs) have gained significant attention as patients use them for glucose control in type 2 diabetes (T2D) and weight management. It is known that these medications have activity in metabolism, inflammation, and some brain pathways, but many patients have reported surprising developments and adverse effects.1 This has prompted researchers to examine them in conditions other than T2D, with some encouraging if not downright welcome results.
Less at the Bar? GLP-1s and Alcohol Consumption
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Could a diabetes drug also curb your craving for a cocktail? Emerging research suggests a surprising link between GLP-1 receptor agonists and reduced alcohol intake, a development with significant public health implications given alcohol’s contribution to 2.6 million deaths globally and 178,000 deaths in the U.S. each year.2-4
A placebo-controlled study involving 48 women struggling with alcohol use disorder found that those receiving weekly injections of semaglutide (Wegovy; Novo Nordisk) drank approximately 30% less on days they consumed alcohol compared to a 2% reduction in the placebo group.5 The semaglutide group also reported fewer heavy drinking days and diminished cravings.5
Analysis of data from the US Department of Veterans Affairs (VA) involving over 215,000 individuals with diabetes initiating GLP-1s revealed a lower likelihood of substance use or psychotic disorders compared to those starting sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter-2 inhibitors, or usual care.6 However, GLP-1 users experienced a higher incidence of arthritic disorders, pancreatitis, gastrointestinal issues, low blood pressure, kidney problems, and fainting.6
Cognitive Function: A More Complicated Picture
Initial optimism surrounding GLP-1s’ potential to slow or reverse cognitive decline stemmed from six preclinical theories.7,8 While VA data indicated fewer seizures and neurocognitive disorders, including Alzheimer’s disease and dementia, among GLP-1 users, recent large-scale trials (over 3,800 participants) showed no significant benefit in slowing disease progression in individuals with early Alzheimer’s disease treated with semaglutide.9,10
Research continues on Parkinson’s disease. A study of 194 participants found no disease-modifying effects with exenatide (Byetta; Amylin Pharmaceuticals, Inc).11 However, a phase 2 trial using lixisenatide showed slowed motor disability progression in patients with early-stage Parkinson’s, though gastrointestinal side effects were common.12,13 This suggests varying effects of different GLP-1s across different conditions.
Hope for Polycystic Ovary Syndrome
A meta-analysis examining GLP-1s in polycystic ovarian syndrome (PCOS) confirmed a positive impact on both weight reduction and hormonal regulation. Among 176 participants, GLP-1 use was associated with significant reductions in waist circumference, body mass index, triglycerides, and testosterone levels.14 A larger meta-analysis of 1476 women yielded similar findings.15
A Multifaceted Class of Drugs
GLP-1s exert influence over numerous biological systems through a single receptor family, demonstrating their pleiotropic nature.16 Ongoing studies are yielding both promising and mixed results. As research accumulates, we’ll gain a clearer understanding of these agents’ potential. For now, off-label use should be guided by a clinician after careful consideration of risks and benefits.
