Patient Factors Influence Semaglutide Initiation After Obesity Diagnosis

Patient factors, including sociodemographic, healthcare, and clinical elements, were linked to the initiation of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in a population with obesity without type 2 diabetes (T2D).1

Among more than 97,000 commercially insured adults in a recent cohort study, approximately 2.0% began semaglutide treatment within 6 months of an obesity diagnosis, with sex, insurance plan, and medication use found to be relevant factors for medication initiation.

“The association of these factors with semaglutide initiation were quantified using multivariable logistic regression, and use of common medications, insurance plan structure, employer industry type, and sex were all significantly associated with semaglutide initiation,” wrote the investigative team, led by Andrew C. Stokes, PhD, department of global health, school of public health, Boston University.

As obesity and overweight affect nearly 74% of individuals in the US, the demand for obesity medications, such as GLP-1 RAs, is growing, with approximately 6% of the US population currently taking one.2 Previously, GLP-1 RAs were exclusively approved to treat T2D, with recent clinical trials reporting their benefit for weight management and cardiovascular disease (CVD) prevention.3

The US Food and Drug Administration (FDA) approved semaglutide (Wegovy) in June 2021 for weight management in individuals with overweight or obesity.4 Populations with obesity, but not diabetes, are a unique population in determining uptake of GLP-1 agonists, with limited evidence on the factors involved in medication initiation. Evidence has, however, suggested this subgroup, at risk of developing diabetes and other cardiometabolic conditions, may be undertreated due to clinician and patient perception of obesity as a risk factor, not a disease.2

For this study, Stokes and colleagues explored patient access to GLP-1 agonists based on individual factors, implementing a machine-learning approach to factor identification and multivariable regression modeling to measure the link between these factors and semaglutide initiation.

Collecting data from the Merative MarketScan Commercial Claims and Encounters Database, the retrospective, observational cohort included US adults aged ≥18 years with a first diagnosis of obesity between June 2021 and July 2022 in an outpatient or inpatient setting. Patients could not have been prescribed prior anti-obesity medications, have undergone bariatric surgery, or had a diabetes claim in the 12 months before obesity diagnosis.

In the analysis, conducted from February to November 2024, Stokes and colleagues utilized a 10-fold cross-validated random forest model examining 698 potential variables associated with incident semaglutide prescription. Among 97,456 individuals who met inclusion criteria, 59.6% were female, 27.3% were aged 45–54, and 52.0% resided in the Southern US.

Approximately half (50.7%) were covered by preferred provider organization plans, but only 2.0% (n = 1963) initiated semaglutide within 6 months of the initial obesity diagnosis. Upon further analysis, the random forest model revealed an area under the receiver operative characteristic (AUROC) curve of 0.71 (95% CI, 0.69–0.74), indicating reasonable discriminative performance.

Stokes and colleagues ranked the top 20 features of the model feature importance list in a Shapley Additive Explanation plot, with the most important exposures including sex, antidepressant use, and employer industry. A multivariable logistic regression model was implemented to quantify the association of the top 20 features with semaglutide initiation. Female sex (adjusted odds ratio [aOR, 2.30; 95% CI, 2.05–2.58), antidepressant use (aOR, 1.62; 95% CI, 1.46–1.78), and insurance plan type, particularly a point-of-service plan (aOR, 1.78; 95% CI, 1.42–2.22), were noted as significant factors.

“These findings suggest that inequities persist in medication access in this understudied subgroup, and further research should investigate factors associated with GLP-1 receptor agonist use in those with public payer plans, as well as whether concurrent use of common medications impacts effectiveness,” they added.

References

1. Podolsky MI, Raquib R, Shafer PR, Hempstead K, Ellis RP, Stokes AC. Factors Associated With Semaglutide Initiation Among Adults With Obesity. JAMA Netw Open. 2025;8(1):e2455222. doi:10.1001/jamanetworkopen.2024.55222
2. Temple NJ. The Origins of the Obesity Epidemic in the USA-Lessons for Today. Nutrients. 2022;14(20):4253. Published 2022 Oct 12. doi:10.3390/nu14204253
3. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
4. Campbell P. Semaglutide (Wegovy) approved for chronic weight management in patients with obesity or overweight. HCP Live. April 17, 2023. Accessed January 21, 2025. https://www.hcplive.com/view/semaglutide-approved-for-chronic-weight-management-in-patients-with-obesity-or-overweight.