Study Suggests Semaglutide May Reduce Opioid Overdose Risk in Patients with Type 2 Diabetes

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Last year, approximately 107,000 people died from drug overdoses in the United States, primarily from opioids. While traditional medications aimed to combat opioid use disorder (OUD) are effective, they are not widely used or adhered to, with nearly half of patients discontinuing treatment within six months, according to a study published in JAMA Network Open.

In light of the ongoing opioid epidemic, the study authors set out to measure the potential of semaglutide as a treatment for OUD. Previously, semaglutide has shown promise reducing cravings in other substance use disorders, such as nicotine and alcohol.

The analysis included a cohort study using electronic health records from the TriNetX Analytics Platform, comparing semaglutide with other antidiabetic medications, including insulin, metformin, and other GLP-1 receptor agonists (RAs), in patients with both T2D and OUD. Participants of the study were evaluated for up to a year after being prescribed semaglutide or other antidiabetic medications, with propensity-score matching used to adjust for differences in baseline characteristics. The primary outcome of the study was opioid overdose, with hazard ratios (HRs) calculated to assess risk reduction.

Implementing a statistical approach similar to a clinical trial, results demonstrated that semaglutide significantly reduced the risk of opioid overdose compared to other GLP-1RAs, such as liraglutide and dulaglutide. HRs ranged from 0.32 to 0.58, indicating a 42% to 68% lower risk of overdose in the semaglutide group. Additionally, semaglutide was associated with a significantly lower risk of opioid overdose during a one-year follow-up. The negative control outcome showed no difference between groups.¹

"Not everyone receives or responds to them," said Rong Xu, research team leader, director, Case Western Reserve University School of Medicine Center for AI in Drug Discovery, in a press release. "As a result, alternative medications to help people treat opioid use disorder and prevent overdosing are crucial. Therefore, our findings suggest that it is important to continue studying semaglutide as a possible new treatment for combating this terrible epidemic."²

Semaglutide, which is the active ingredient in Novo Nordisk’s Wegovy and Ozempic, has also demonstrated potential in not only supporting weight loss, but in indications such as kidney failure, obesity, heart failure, and the aforementioned type 2 diabetes. As a result of its popularity, Novo Nordisk is now the largest company in Europe, currently valued at approximately $433 billion.³

This year, the FDA also added Wegovy as a treatment for reducing the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease who are also obese or overweight. When used in combination with a reduced calorie diet and increased physical activity, it was the first treatment indicated for reducing cardiovascular events and for long-term weight management. In a recent interview with Pharm Exec, Sylvia Shubert, US therapeutic area head for obesity in commercial strategy and marketing, Novo Nordisk, stated that while Wegovy has always had a high level of interest, the new indication has only enhanced its popularity.⁴

The authors of the study said that based on the findings, semaglutide could have therapeutic potential in reducing opioid overdose risk in patients with comorbid type 2 diabetes and OUD. Despite this, the authors warn that the study's observational design may introduce biases, and further research, including randomized clinical trials, is needed to validate these results and explore the underlying mechanisms of semaglutide's effects on opioid use.¹

References

1. Semaglutide and Opioid Overdose Risk in Patients With Type 2 Diabetes and Opioid Use Disorder. JAMA. September 25, 2024. Accessed September 26, 2024. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2824054?guestAccessKey=67ec89b0-a682-4fbf-97d9-1c0054b62d04&utm_source=for_the_media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=092524

2. Popular diabetes and weight-loss drug associated with lower opioid overdose risk, study finds. Science Daily. September 25, 2024. Accessed September 26, 2024. https://www.sciencedaily.com/releases/2024/09/240925122853.htm

3. The Impact of GLP-1 Weight Loss Drugs on Patients, Healthcare Business. PharmExec. November 2, 2023. Accessed September 26, 2024. https://www.pharmexec.com/view/the-impact-of-glp-1-weight-loss-drugs-on-patients-healthcare-business

4. Branching Off: Wegovy. Pharm Exec. August 16, 2024. Accessed September 26, 2024. https://www.pharmexec.com/view/branching-off-wegovy