US, Japan Patients With Diabetes Discontinue Semaglutide After First Year

Nearly 6 in 10 older US adults with diabetes discontinue injectable semaglutide within 1 year of starting it, according to a new study in JAMA Cardiology.¹ The research, which also examined data from Japan, found a similar, though less pronounced, trend, with about three in 10 Japanese patients stopping the therapy in the same timeframe.

The findings echo recent research from Denmark showing more than half of first-time users stop taking the popular glucagon-like peptide-1 receptor agonist (GLP-1 RA) after a year, highlighting a global challenge to patient persistence that could limit the drug's significant health benefits.²

The studies point to several key factors driving these high discontinuation rates, with out-of-pocket costs and medication intolerance being primary concerns. The JAMA Cardiology study found that in the US, patients dually enrolled in Medicare and Medicaid—who typically have lower medication co-payments—were significantly less likely to discontinue semaglutide.¹ Researchers suggest the lower discontinuation rate in Japan (30.8%) compared to the US (59.5%) may also reflect lower patient cost-sharing in Japan's health care system.

This financial barrier was also a major factor in the Danish study, where patients pay for the medication out-of-pocket.² The analysis found that users in low-income areas were 14% more likely to stop treatment within the first year.

Troublingly, patients who stand to gain the most from GLP-1 RAs are among those most likely to discontinue.^1,2 In both the US and Japan, individuals with pre-existing chronic kidney disease and cardiovascular disease were more likely to stop therapy.¹ This is a critical issue, as these high-risk patients would be expected to derive substantial clinical benefits from continued treatment. The Danish study also noted that patients with cardiovascular disease or other chronic conditions were 10% more likely to discontinue within a year.²

Adverse effects are another significant hurdle. The Danish research found that patients who had previously taken gastrointestinal medication were more susceptible to common side effects like nausea and vomiting and were 9% more likely to stop treatment.

Senior author of the Danish study Reimar W. Thomsen, PhD, from the Department of Clinical Epidemiology at Aarhus University Hospital in Aarhus, Denmark, told The American Journal of Managed Care^® (AJMC^®) that patients often stop treatment, noting it is often a combination of “having the side effects but also being disappointed due to a combination of maybe not feeling well and not losing the weight.”

The consequences of discontinuing therapy are stark, as demonstrated in the STEP 1 trial extension study published in Diabetes, Obesity and Metabolism.³ The study followed participants for a year after they stopped taking semaglutide and found that they regained, on average, two-thirds of the weight they had previously lost.

Furthermore, the significant improvements in cardiometabolic health seen during treatment—such as lower blood pressure, cholesterol, and hemoglobin A_1c levels—largely reverted toward baseline after withdrawal. While some benefits were sustained a year later, the findings confirm that obesity is a chronic disease requiring ongoing treatment to maintain improvements in weight and health.

Taken together, the data from the US, Japan, and Denmark paint a clear picture: without better strategies to support long-term adherence, the transformative potential of semaglutide may go unrealized for many.^1,2 Researchers from the JAMA Cardiology study conclude that the high discontinuation rates highlight the need for "concerted global efforts to support persistence with semaglutide," particularly by minimizing cost-sharing to improve affordability for high-risk populations.¹

References

1. Inoue K, Decker SRR, Shi I, et al. Discontinuation of semaglutide among older adults with diabetes in the US and Japan. JAMA Cardiol. Published online September 24, 2025. doi:10.1001/jamacardio.2025.3109

2. McCrear S. GLP-1 RA adherence shows drop-off after 1 year. AJMC^®. September 16, 2025. Accessed September 24, 2025. https://www.ajmc.com/view/glp-1-ra-adherence-shows-drop-off-after-1-year

3. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725