GLP-1 Agonists May Help Treatment of Mental Illness and Substance Use

The fight for access to obesity treatment is also a fight for mental health.

Reviewed by Monica Vilhauer

Key points

• GLP-1 agonists are popular agents for weight loss.
• Agents like semaglutide show promise for treatment of substance use disorders.
• Inaccessibility of GLP-1 agonists due to high prices limits their potential public health impact.

Last week, Vermont Senator Bernie Sanders pressed the chief executive officer of Novo Nordisk to lower prices of popular weight-loss drugs such as semaglutide – marketed in the United States as Wegovy and Ozempic. The September 24^th hearing interested many Americans currently struggling with the high cost of obtaining these drugs to aid their own weight loss journeys. Senator Sanders’ advocacy is welcome, but some may not realize that his effort to hold Novo Nordisk accountable also helped advance the care of those struggling with mental illness and addiction.

The popularity of semaglutide and other glucagon-like peptide-1 (GLP-1) agonists that promote weight loss cannot be underestimated. A 2022 study in Nature demonstrated a mean decrease of 15.2% of body weight across 104 weeks of follow-up among users of semaglutide compared to only a 2.6% reduction in weight among the placebo group. For many Americans who have either had no success with lifestyle modifications or seen their weight loss journeys turn stagnant, Wegovy and Ozempic offer life-changing hope and promise.

Patients with schizophrenia have nearly five times the prevalence of diabetes and obesity in comparison to others in the general population. Weight gain often accompanies pharmacological treatment of schizophrenia, which further compounds the problem. Nonadherence to treatment frequently results, leading to mental health decompensation. In recent years, studies examining the use of semaglutide and other (GLP-1) agonists (e.g., luraglutide) have demonstrated these agents are effective in limiting antipsychotic-induced weight gain. These findings have significant import for patients on antipsychotic therapy who may otherwise not seek care because of worries about weight gain.

The potential benefit of GLP-1 agonists in mental health care may further extend beyond their utility in weight loss. A May 2024 study in Nature of over 80,000 patients with obesity showed that semaglutide usage was associated with a 50-56% lower risk for incidence and recurrence of alcohol use disorder over a one-year follow-up. Research also suggests that GLP-1 agonists may decrease nicotine cravings. Individuals who quit smoking typically gain 8-11 pounds during the first six months following an attempt to quit, a common enough concern that dissuades some from trying to stop at all. GLP-1 agonists that both promote weight loss while decreasing tobacco use have significant potential to catalyze tobacco cessation attempts, leading to higher quit rates and lower tobacco-associated medical comorbidities such as cardiovascular disease and cancer.

Significant price disparities for prescription drugs are often the norm rather than the exception in the United States. In the Senate hearing in late September noted above, the cost of Ozempic was cited as nine times more expensive in the United States ($969) than in Germany ($59). Current US pricing of Wegovy at $1,349 far surpasses the cost of the same drug in Denmark ($186) and makes acquiring this medication out of reach for many.

Of course, the popularity and efficacy of GLP-1 agonists for weight loss must be balanced against risk of known side effects. Gastrointestinal distress, including nausea, vomiting, and acute pancreatitis is more common with use of GLP-1 agonists. In December 2023, the US Food and Drug Administration’s Adverse Events Reporting System observed a disproportionate increase in suicidal ideation with GLP-1 agonists, although no corresponding rise in suicidal behavior, attempts, or completed suicides was noted. The rate of occurrence of these side effects was low, but more widespread use of GLP-1 agonists in the general population means that these adverse effects will be more visible.

GLP-1 agonists represent a turning point in the pharmacological treatment of obesity. Their potential benefit and reach may well extend beyond obesity. However, popularity and desirability should not eclipse the need for due diligence and further investigation. Clinical equipoise must dictate the future role of GLP-1 agonists in the treatment of other medical and psychiatric conditions. Should future study on these agents be encouraging, the opportunity for meaningful and consequential impact on the nation’s public health should not be overshadowed by price gouging and economics. Drug manufacturers should know that consumers – and Congress – are watching closely.