The Association Between Semaglutide Initiation and Obese Individuals Without Diabetes
What factors influence their likelihood of receiving this form of obesity treatment?
It could be argued that the demand for glucagon-like peptide-1 (GLP-1) receptor agonist medications such as semaglutide (Ozempic or Wegovy, both of which made the Centers for Medicare & Medicaid Services’ latest list of Part B and D drugsto be covered under this plan for price negotiations1) and tirzepatide (Mounjaro or Zepbound) has grown exponentially in the United States.
Approximately 6% of the US population reports currently taking a GLP-1 receptor agonist, although the proportion of people who report being told by a physician that they have overweight or obesity nears 1 in 5.2 However, despite these numbers, the Centers for Disease Control and Prevented notes that 73.6% of the US population has overweight or obesity.3 Many may remember that GLP-1 receptor agonists had been previously approved for the treatment of type 2 diabetes, but that has since changed; more recent clinical trials have been demonstrating that this drug class has been effective toward treating weight management and cardiovascular disease prevention, resulting in FDA approving these indications.4
Keeping this in mind, those individuals with obesity but not diabetes represent a smaller subgroup. A cohort study published in JAMA Network Open5 sought to explore this further by taking a deeper dive into the factors that are associated with semaglutide initiation in these specific individuals. What exactly influences their likelihood of receiving this form of obesity treatment?
In analysis that occurred from from February to November 2024, the retrospective observational study pulled data from the Merative MarketScan Commercial Claims and Encounters database from the June 5, 2020, through Dec. 31, 2022 timeframe. Adults in this database are 18 years of age or older, with a first diagnosis of obesity in an outpatient or inpatient setting between June 5, 2021, and July 1, 2022.
Further, in order to be included in the study, the 97,456 selected individuals were to have not been on any prior anti-obesity medication, GLP-1, no bariatric surgery, or not diabetes-related claim in the 12 months before obesity diagnosis, and continuous enrollment in the 12 months before and six months after the obesity diagnosis.
Overall, 58,124 individuals (59.6%) were female, 26,582 (27.3%) were aged 45 to 54 years, 49,390 (50.7%) were covered by their preferred provider organization plans, and 50,705 (52.0%) lived in the South. Out of the total sample size, 1,963 (2.0%) began semaglutide within six months of their initial obesity diagnosis. The random forest model had an area under the receiver operating characteristic curve of 0.71 (95% confidence interval or CI, 0.69-0.74).
Shapley Additive Explanations—a method of explaining how machine learning models make predictions—recognized various exposures, including sex, use of antidepressants, and the industry that the employer operates in. In the logistic regression model, the top 20 factors were used, which found significant associations with semaglutide initiation, including being female (adjusted odds ratio [aOR], 2.30; 95% CI, 2.05-2.58), use of specific medication classes, such as antidepressants (aOR,1.62; 95% CI, 1.46-1.78), and being covered by a point-of-service plan (aOR, 1.78; 95% C, 1.42-2.22).
The study investigators concluded that, “In this retrospective observational cohort study of commercially insured individuals with obesity and without diabetes, we identified sociodemographic, healthcare, and clinical factors associated with semaglutide initiation within six months after obesity diagnosis using a novel machine learning approach. The associations 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.
“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.”
References
1. Saraceno N. Headlined by Ozempic, Medicare Reveals Second Round of Drugs Selected for Price Negotiations. Pharmaceutical Commerce. January 17, 2025. Accessed January 22, 2025. https://www.pharmaceuticalcommerce.com/view/medicare-drug-price-negotiations
2. Montero A, Sparks G, Presiado M, Hamel L. KFF health tracking poll May 2024: the public’s use and views of GLP-1 drugs. KFF. Published May 10, 2024. Accessed May 21, 2024. https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-may-2024-the-publics-use-and-views-of-glp-1-drugs/
3. National Center for Health Statistics. Obesity and overweight. Centers for Disease Control and Prevention. Updated October 25, 2024. Accessed December 5, 2024. https://www.cdc.gov/nchs/fastats/obesity-overweight.htm
4. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al; SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
5. 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
