GLP-1 Drugs Show Protective Effects Against Addictions, Parkinson's, and Endometrial Cancer
New research reveals GLP-1 receptor agonists reduce substance use disorders by 14%, lower Parkinson's disease risk after 5-10 years of use, and cut endometrial cancer risk by 66% when combined with progestin therapy.
Ozempic, Mounjaro and other GLP-1 drugs for diabetes can prevent the formation of new substance use disorders and alleviate existing addictions, according to findings from a large study of U.S. military veterans. The protective effect was seen across a wide variety of addictive and habit-forming substances, including cocaine, opioids, alcohol, nicotine and cannabis.
The study used a U.S. Veterans Affairs database to identify patients with type 2 diabetes treated with drugs from two different classes of medicines: GLP-1s such as Trulicity, Mounjaro, Victoza or Ozempic; and SGLT-2 inhibitors such as Jardiance and Farxiga. The 124,001 participants without a history of substance abuse who were taking GLP-1 drugs had 14% lower odds of developing a new substance use disorder over the following three years than the 400,816 similar patients prescribed SGLT-2 inhibitors.
GLP-1 drugs reduced the odds of new alcohol use disorders by 18%, cannabis use disorders by 14%, cocaine use by 20%, nicotine use by 26%, and opioid use by 25%, the researchers found. Among 81,617 patients with existing substance use disorders, the odds of related emergency department visits during the next three years were 31% lower for those on GLP-1s. GLP-1 drugs also reduced related hospital admissions by 26% versus the SGLT-2s, related deaths by 50%, drug overdoses by 39%, and suicidal ideation or attempt by 25%.
The proteins on brain cells that receive chemical signals from GLP-1 drugs, known as GLP-1 receptors, are found in an area called the mesolimbic system that is responsible for motivation and reward signaling. The GLP-1 drugs are likely acting in the mesolimbic system to "put the lid on cravings" by silencing the noise in people's brains that drive them toward overuse of foods or drugs. The findings were published in The BMJ.
In separate research published in Diabetes, Obesity and Metabolism, GLP-1 receptor agonist therapy may reduce Parkinson disease risk among patients with type 2 diabetes. Investigators sourced data from the TriNetX Global Collaborative Network, comparing patients with type 2 diabetes who initiated a GLP-1RA between 2005 and 2025 (n=92,485) with those who initiated metformin (n=92,485).
The rate of incident Parkinson disease was 0.31% among matched GLP-1RA users and 0.67% among matched metformin users. Overall, no significant difference in Parkinson disease risk was observed between medication cohorts. However, in the time-stratified analysis, the researchers observed no between-group differences in Parkinson disease risk within the first 5 years of use or with more than 10 years of use. At 5 to 10 years, Parkinson disease risk was lower with GLP-1RA use compared with metformin (adjusted hazard ratio, 0.56; 95% CI, 0.34-0.93; P =.0239).
In the subgroup analyses, GLP-1RA use was associated with lower risk for Parkinson disease among women (adjusted hazard ratio, 0.80; 95% CI, 0.64-0.99; P =.0372) and patients with hypertensive diseases (adjusted hazard ratio, 0.81; 95% CI, 0.68-0.98; P =.0253).
A third study published in JAMA Network Open found that GLP-1 receptor agonists in combination with a progestin reduced the risk of endometrial cancer by approximately 66%. The retrospective cohort study collected data from 444,820 patients from TriNetX to analyze endometrial cancer and hysterectomy among adult women with endometrial hyperplasia or benign uterine pathology who received progestins between May 1, 2005, and December 31, 2022.
Of the population, 18,414 patients received GLP-1 RAs in combination with progestin and 426,406 received progestin alone (mean age, 43.1 years vs 35.2 years). The data showed a clinically meaningful association between GLP-1 RAs with progestins and lower endometrial cancer risk (HR, 0.34; 95% CI, 0.27-0.44), which remained consistent across subgroups, stratified by progestin route, baseline risk, BMI, and age.
The authors also observed a lower endometrial cancer risk with GLP-1 RAs compared with metformin plus progestins (HR, 0.30; 95% CI, 0.15-0.59). Triple therapy (GLP-1 RA, metformin, and progestins) demonstrated greater reductions in endometrial cancer risk compared with dual therapy (metformin plus progestins; HR, 0.37; 95% CI, 0.25-0.53) and progestin monotherapy (HR, 0.44; 95% CI, 0.29-0.66).
In addition, patients receiving GLP-1 RAs with progestins experienced lower hysterectomy rates at both 2 years (HR, 0.47; 95% CI, 0.42-0.53) and 5 years (HR, 0.59; 95% CI, 0.54-0.64). Prior data show that GLP-1 RAs, when combined with a progestin, can significantly upregulate PR expression, reduce cell viability in endometrial cancer organoids, and improve progestin responsiveness even in malignant neoplasms with low baseline PR levels.
The VA itself is planning a large, traditional clinical trial testing semaglutide, the main ingredient in Ozempic and Wegovy, in U.S. veterans with alcohol use disorder.