Semaglutide Behind Huge Increase in GLP-RA Prescriptions with Fewer Written for Type 2 Diabetes

Among the nearly 872 000 individuals in the US who received a first-time prescription for a glucagon-like peptide-1 receptor agonist (GLP-1 RA) between 2011 and 2023, a decreasing proportion of the new users had type 2 diabetes (T2D) but there was a twofold increase in the proportion of users without T2D but with a BMI indicative of obesity (equal to or greater than 30 kg/m²) or of overweight (27 to 30 kg/m²) plus an obesity related comorbidity.

The findings, published in a Brief Research Report in the Annals of Internal Medicine, were reported by researchers from Cedars Sinai Medical Center in Los Angeles.

Overall annual prescribing of new GLP-1 RA rose from 0.5% in 2019 to more than 3% in 2023 with the greatest increase, more than 600 000, recorded between 2019 and 2023, according to the authors. They suggest that the surge during that time reflected the expanded approval of the medications by the US FDA in 2021 for chronic weight management, following original approvals for the class to reduce hyperglycemia in individuals with T2D.

Semaglutide accounted for more than 88% of new GLP-1 RA prescriptions in 2023, an increase from 31.4% in 2019, researchers found. The incretin mimetic was approved for chronic weight management in 2021 after initial labeling for T2D management in 2017.

“Essentially, after the medication was approved for obesity, GLP-1 RA use took off so quickly that we lost control and vision of how fast people were picking up these medications, and the trends of use are uncertain,” study co-first author Ali Rezaie, MD, medical director of the Cedars-Sinai GI Motility Program and director of bioinformatics at the Medically Associated Science and Technology program at Cedars-Sinai, said in a news release. “While GLP1-RAs offer several benefits, they are also associated with various common and uncommon side effects, necessitating careful monitoring of their prescription patterns.”

“Essentially, after the medication was approved for obesity, GLP-1 RA use took off so quickly that we lost control and vision of how fast people were picking up these medications, and the trends of use are uncertain."

The greater use of the medications for treating obesity points to the clinical benefits that health care providers are seeing, “which is a significant public health shift,” Rezaie’s co-first author Yee Hui Yeo, MD, a clinical fellow in the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai, commented in the release. “However, it also raises concerns about potential medication shortages and the need to ensure that patients with diabetes still have access to these treatments.”

Indeed, the surge in demand for GLP-1 RA medications has led to significant shortages, making it even more crucial to build data on trends in how and for whom they are being prescribed, information the authors have found is scarce.

For their investigation, Rezaie, Yeo, and fellow researchers tapped data from TriNetX, a federated research network of deidentified records of 45 million individuals with at least 1 outpatient or inpatient visit in the US between 2011 and 2023. The diversity of the data spans geography, age, ethnicities, income, and insurance type, according to the study.

After delineating annual trends in new GLP-1 RA prescriptions over the 12-year period, they categorized each by the presence of T2D and comorbidities related to T2D or obesity. Overall, there were 871 854 new users. Between 2011 and 2014, there were 27 367 new users followed by a significant increase to 131 029 between 2015 to 2018. From 2019 to 2023, the number of new prescriptions spiked to 679 265, the authors reported. They also documented an increase in the proportion of new GLP-1 RA users without an FDA-approved indication for the medications, from 0.21% in 2019 to 0.37% in 2023.

When they examined the characteristics of the population Rezaie et al found that first-time GLP-1 RA users skewed disproportionately female, non-Hispanic White, and had a BMI of equal to/greater than 30 kg/m2. The average age at the time of the index prescription was 54.6 years. In terms of comorbidities, more than half (59.5%) had T2D and a greater proportion (61.3%) had hypertension. Approximately 1 in 5 (17.9%) had ischemic heart disease, and just fewer than 1 in 10 (9.3%) had cerebrovascular disease.

First-time GLP-1 RA users skewed disproportionately female, non-Hispanic White, and had a BMI of equal to/greater than 30 kg/m². The average age at the time of the index prescription was 54.6 years.

The researchers express concern that the magnitude of the obesity epidemic in the US will lead to even greater demand for GLP-1 RA medications for weight management, precipitating ongoing drug shortages that in turn have the potential to exacerbate the existing nationwide racial and ethnic disparities in prescriptions for the incretin mimetics. "The recent approval of tirzepatide for weight control in persons without diabetes and the FDA approval of the use of GLP-1 RAs to reduce cardiovascular disease risk will further broaden the indications of GLP-1 RAs and affect access," the researchers pointed out.

Their findings, they concluded, “call for strategies to address the growing demand and ensure equitable access to GLP-1 RAs.”

References

1. Yeo YH, Rezaie A, Hsieh TY-J. Shifting trends in the indication of glucagon-like peptide-1 receptor agonist prescriptions: a nationwide analysis. Ann Intern Med. 2024; doi:10.7326/M24-0019
2. New Cedars-Sinai study investigates shifting trends in GLP-1RA prescription. News release. Cedars Sinai. July 22, 2024. Accessed July 23, 2024. https://www.cedars-sinai.org/newsroom/new-cedars-sinai-study-investigates-shifting-trends-in-glp-1ra-prescription/