Ali Rezaie, MD: Trends in GLP-1RA Use Among Nondiabetic, Nonobese Patients

Concerning trends have been identified in the prescription of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) across the United States, according to a new analysis presented at Digestive Disease Week (DDW) 2024.¹

With data from millions in a population-based cohort up to August 2023, GLP-1 agonist prescriptions were most common among younger people and those who did not meet label recommendations, which could deny access to patients who may benefit from their use.

In an interview with HCPLive, Ali Rezaie, MD, medical director of gastroenterology motility at Cedars-Sinai, called for vigilance about GLP-1 agonist use in patients without these indications, noting the existence of side effects and the far-reaching effects of drug shortages from this misuse.

In particular, he stressed the need for medical societies outside the framework of endocrinology and primary care that deal with these side effects, including gastroenterology, to offer guidance and education on GLP-1 agonist use.

“This is a call for those societies to come up with some guidelines for position statements, at least, to educate the members about what needs to be done with these medications,” Rezaie told HCPLive. “Just because it’s an endocrinology drug doesn’t mean that gastroenterology shouldn’t know about — actually, we should know even more detail on what’s going on with them.”

The GLP-1 agonist medication class was approved by the US Food and Drug Administration (FDA) during the past 10 years for managing obesity or overweight in the presence of ≥1 weight-related comorbidity, including liraglutide in 2014 and semaglutide in 2021.² In the time since approval, numerous gastrointestinal side effects have been reported with GLP-1 agonist use. Recent surges in prescriptions have led to medication shortages, particularly for semaglutide.

Given the limited data on the appropriate prescription patterns of GLP-1 agonists, Rezaie and colleagues evaluated the national trend in GLP-1 prescription patterns using the TriNetX database. Trends in new prescriptions of GLP-1s were observed between January 2011 and December 2022 and monthly trends from August 2021 to August 2023.

A total of 742,286 GLP-1 agonist users were identified in the database. Overall, there was a significant increasing annual trend in new GLP-1 agonist prescriptions from 2011 to 2022 (annual percentage change [APC], 27.8%; 95% CI, 12.5 – 33.0). The trend accelerated after a joinpoint in 2020 (APC, 65.7%) and the monthly data showed a significant rise between November 2022 and August 2023 (monthly percentage change, 15.0%; 95% CI, 12.0 - 20.4).

Younger individuals (age ≤40 years) experienced the sharpest upward trend in new GLP-1 prescriptions, and significant upward trends were identified across all body mass index (BMI) categories, including individuals with normal BMI. Notably, the increase in GLP-1 prescriptions was more pronounced among people without diabetes (APC, 69.8%) than those with diabetes (APC, 18.3%).

“We have to pay more attention to the demand that is on-label as opposed to off-label and these shortages have happened multiple times over the last few months,” Rezaie told HCPLive. “That’s key to make sure people who truly need it and they’re benefiting from it, not to get their hands empty of these medications while they are used off-label for other uses.”

Disclosures: Rezaie reports relevant disclosures including Ardelyx, Vibrant, and Bausch Health.

References

1. _{Yeo YH, Rezaie A, Hsieh TY, Hu X, Mohamed G, Lee GY, Huang PC, Watson R, Gaddam S, Ma KS. Steep Increase in Usage of Glucagon-Like Peptide-1 Receptor Agonists in Non-Diabetic and Non-Obese Individuals in the United States. Lecture presented at Digestive Disease Week 2024, May 18 - 21, 2024.}
2. _{Jensterle M, Rizzo M, Haluzík M, Janež A. Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review. Adv Ther. 2022;39(6):2452-2467. doi:10.1007/s12325-022-02153-x}