Plain Language Summary
Analysis of time- and sex-specific factors associated with GLP-1 RA utilization in the US, examining why women consistently outnumber men in GLP-1 RA prescribing despite similar or greater cardiovascular benefit in men. Reviews prescribing data and sociocultural, clinical, and health system factors driving the sex utilization gap. Identifies actionable drivers of underutilization in men—a clinically important population where semaglutide's SELECT cardiovascular benefits may be disproportionately undersupported by prescribing rates, informing targeted health equity interventions.
Abstract
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a modern class of medications initially approved for type 2 diabetes mellitus (T2DM) but now also widely used for obesity. Although these drugs offer significant benefits for glycemic control, weight loss, and cardiorenal health, studies consistently show a pronounced sex difference in their use. However, there is a scarcity of studies addressing the factors responsible for these sex differences in GLP-1RA utilization in the United States.
OBJECTIVE: To examine time- and sex-specific factors associated with GLP-1RA utilization among US adults before and after the landmark approval of semaglutide for chronic weight management.
METHODS: We analyzed data from the 2019-2022 Medical Expenditure Panel Survey, a nationally representative survey of US adults (aged ≥18 years). GLP-1RA use was identified via prescription drug files. Descriptive statistics and chi-square tests compared characteristics of GLP-1RA users by time and sex. Multivariable logistic regression models estimated associations between individual characteristics and GLP-1RA use, both overall and among time- and sex-stratified cohorts. Subgroup analysis was conducted in adults with T2DM.
RESULTS: The weighted prevalence of GLP-1RA use increased significantly from 6,158,326 (0.47%) in 2019-2020 to 10,410,021 (0.79%) in 2021-2022 ( < 0.0001). The rate of use was 0.48% and 0.46% in women and men, respectively, in 2019-2020 ( = 0.837) and increased to 0.82% in women and 0.76% in men in 2020-2022 ( = 0.964). T2DM was the strongest predictor of GLP-1RA use (odds ratio [OR] = 56.1 [2019-2020] and OR = 32.7 [2021-2022]), but the proportion of users with T2DM slightly decreased over time (92.8% in 2019-2020 to 90.2% in 2021-2022 [ = 0.239]). This decrease was especially pronounced in women during the 2021-2022 period, with men exhibiting a notably higher proportion of T2DM patients (94.4%) compared with women (86.2%) ( = 0.002). The proportion of users with obesity increased significantly (5.3% to 9.2%, = 0.024), nearly doubling among female users (4.9% to 10.6%). The association with obesity strengthened over time (OR = 1.85 to 5.59), especially among women (OR: 6.43 vs 2.04 in men). Among women, depression was linked to greater use. In patients with T2DM, the use of insulin and oral antidiabetic medications was associated with higher GLP-1RA utilization.
CONCLUSIONS: This study confirms the increasing utilization of GLP-1RAs in the United States, particularly among women. Although type 2 diabetes remains the primary predictor of GLP-1RA use, obesity has emerged as a key associated factor, especially among women. The stronger associations observed in women with obesity and depression highlight the role of clinical and psychosocial factors, which underscores the need for sex-sensitive approaches in obesity and diabetes management.