Trends in Glucagon-Like Peptide 1 Receptor Agonist Prescribing Patterns

ABSTRACT

Objective: Obesity affects more than 40% of US adults, increasing risks for cardiovascular disease and type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), initially indicated for diabetes, show promise in weight loss but face coverage issues, high costs, and premature prescribing from physicians. Research is needed to assess prescribing patterns, especially in patients without diabetes.

Study Design: We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization and expenditures. We analyzed GLP-1 RA prescribing rates from 2018 to 2023, comparing semaglutide with other GLP-1 RAs and stratifying by diabetes and overweight/obesity indications.

Methods: The study included individuals 18 years or older with 12 months of continuous enrollment from 2018 to 2023, categorizing GLP-1 RA users into 4 groups based on diabetes and obesity/overweight diagnosis codes within a year of their index date.

Results: Prescribing of GLP-1 RA medications, particularly semaglutides, increased notably over the years, whereas dulaglutide, liraglutide, and exenatide use declined. When investigating possible premature prescribing by examining users with no diabetes indication, the number of prediabetes or abnormal glucose diagnoses increased slightly before the index GLP-1 RA prescribing index date. However, less than 9% received a diabetes or prediabetes diagnosis 30 days after starting a GLP-1 RA.

Conclusions: From 2018 to 2023, GLP-1 RA prescribing increased significantly, with semaglutide approved for weight loss rising to 60% share in the nondiabetic obese/overweight group. Trends showed a notable rise in prescriptions for nondiabetic and obese/overweight patients.

Am J Manag Care. 2025;31(8):In Press

Takeaway Points

Obesity affects more than 40% of US adults, raising the risk of other chronic conditions and health care costs. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), especially semaglutide, initially used for diabetes, show promise in weight loss. Using Merative MarketScan databases, this study explored the rising trends in GLP-1 RA prescriptions. Barriers include high costs and limited insurance coverage.

Managed care decision-makers should consider the following steps:

• Given the rapidly increasing trend in GLP-1 RA prescribing, assess its potential impact on health care affordability and budget planning.
• Establish patient eligibility and utilization management for safety.
• Monitor prescribing behavior to track adverse effects, discontinued usage, and off-label usage.

Obesity is a chronic, potentially preventable condition with a prevalence greater than 40% among adults in the US.¹ Significant changes in the modern food environment, food processing, and eating behavior over the last decades, including the availability of ultraprocessed food and drinks with high levels of sugar, salt, and fat, and low micronutrients, have contributed to the epidemic of obesity in the US.²

Obesity is a metabolic disorder that is associated with increased risk and subsequent poorer management of cardiovascular disease and type 2 diabetes, thus increasing morbidity and health care costs.³ Although challenging for many patients, reducing body weight may improve clinical outcomes.⁴ Amid this prevalence of obesity, a relatively new class of medications has sparked interest as holding promise for weight loss. Long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat type 2 diabetes, have recently gained significant attention for their potential effectiveness in weight loss. This emerging class of medication shows promise in improving health outcomes by reducing weight and addressing diabetes and other obesity-related conditions, but it requires long-term commitment.^5,6

Semaglutide, a relatively new but prominent GLP-1 RA, has come into the spotlight following its approval by the FDA for weight management in 2021 under the brand name Wegovy. This once-weekly subcutaneous injectable drug, which mimics the natural GLP-1 hormone and activates GLP-1 receptors in the gastrointestinal tract, pancreas, and brain in response to food,⁷ was initially used solely for diabetes treatment. It is the first weight-management drug approved since the FDA approved liraglutide (Saxenda) in 2014 for chronic weight management. In addition to Wegovy, some providers may prescribe other semaglutides, Ozempic and Rybelsus, currently approved only for type 2 diabetes, for off-label use among those without diabetes or with low risk for cardiovascular complications.^8,9 Historically, insurance covered certain treatments for obesity, such as obesity screening, behavioral counseling, and bariatric surgery, but not medications prescribed for weight loss.¹⁰ Treatment of obesity, including weight loss medications, may benefit patients and the health care system in the long term.^11,12 Chronic conditions associated with obesity progressively compound over time, leading to high health care spending later in life. This could be a significant consideration for managed care organizations or systems with capitated payments.¹³ GLP-1 RAs have shown effectiveness in reducing weight in individuals with obesity and in slowing the progression of obesity-related medical conditions.¹⁴ Although these medications hold promise for those affected, the long-term effects and their impact on obesity-related comorbidities remain uncertain due to the evolving evidence, and further research with larger sample sizes and follow-up periods is needed.^3,15,16 Researchers and clinicians are optimistic about the effectiveness of this class of drugs for weight loss, but there are access concerns due to high costs and variation in insurance coverage for weight loss medications.¹⁷ There is an ongoing debate about whether Medicare or other payers will cover medications for weight loss, although these changes would not be effective immediately. Therefore, the high cost and discrepancies in coverage among payers have limited the medications’ use for weight loss purposes to only those who can afford it,¹⁰ contributing to potential sociodemographic and geographic disparities in obesity treatment.

There needs to be more knowledge regarding the prescribing patterns and medication utilization among GLP-1 RA users and the amount of potential off-label prescribing. This study aimed to evaluate the proportion of semaglutide and other GLP-1 RAs prescribed among GLP-1 RA users stratified by diabetes and obesity status and to identify trends in GLP-1 RAs prescribed in nondiabetic patients. We also aimed to identify any patterns for off-label prescribing of GLP-1 RAs for individuals without type 2 diabetes. In this study, off-label prescribing means prescribing Ozempic or other GLP-1 RAs approved for diabetes only to individuals without diabetes or prescribing GLP-1 RAs approved for weight loss to patients without an obesity/overweight diagnosis.

METHODS

Research Design and Data Set

We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization, expenditures, and enrollment across inpatient, outpatient, prescription drug, and carve-out services. This claims data set comes from large employers, health plans, and government and public organizations. The Medicare Database captures fee-for-service claims for Medicare-eligible retirees with employer-sponsored Medicare supplemental and Medicare Advantage plans. The annual medical databases include private-sector health data from approximately 350 payers. These data are licensed by and housed at the UTHealth School of Public Health Center for Health Care Data.

Study Cohort and Measures

The initial sample included individuals 18 years and older with 12 months of continuous enrollment before the index date from 2018 to 2023. For each member, an index date was established by taking the minimum date from all GLP-1 RAs’ prescription-filled dates for each patient. GLP-1 RA prescription was identified using the 2024 Healthcare Effectiveness Data and Information Set list of National Drug Codes (NDCs) and supplemental NDC directory from the FDA.

GLP-1 RA users were then categorized into 4 study groups at the yearly level based on whether they had a diagnosis code for diabetes or obesity/overweight within 365 days (1 year) of the index date: (1) members who had an International Statistical Classification of Diseases, Tenth Revision diagnosis code for diabetes (E10x, E11x, and E13x) in at least 1 inpatient or outpatient claim and no obesity/overweight diagnosis code (Z682x, Z683x, Z684x, E660x, E663, E669); (2) members who had a diagnosis code for diabetes and a diagnosis code for obesity/overweight; (3) members who did not have a diagnosis code for either condition; and (4) members who did not have a diagnosis code for diabetes but had an obesity/overweight diagnosis code. For GLP-1 RAs approved for weight loss (eg, Wegovy), on-label use includes individuals with obesity or overweight with weight-related comorbidities. Because claims data lack details such as laboratory results or family history, we took a conservative approach by grouping obesity and overweight to avoid misclassifying appropriate use. Off-label prescribing of weight loss drugs was defined as use in individuals without obesity or overweight. In addition, among groups 3 and 4, who had no diagnosis code for diabetes, we also investigated individuals diagnosed with prediabetes (R73.03) and the presence of abnormal glucose (R73x) on or 365 days before the yearly index date. In addition, we evaluated whether they had a diagnosis code for diabetes, prediabetes, or abnormal glucose within 90 days after their yearly index date.

Statistical Analysis

First, we evaluated overall rates of prescribing GLP-1 RAs in the initial study population of all members 18 years and older. Then, we stratified rates to compare rates of semaglutide prescribing vs other GLP-1 RA medications between 2018 and 2023. Second, we evaluated annual trends of prescribing individual GLP-1 RA medications (substance name and brand names) among GLP-1 RA users by calculating the number of users and percentage for each GLP-1 RA and stratified by the 4 study groups. To compare semaglutide usage vs other GLP-1 RAs, each member each year was assigned to 1 GLP-1 RA drug group based on their yearly index date. If a member had a filled prescription for more than 1 GLP-1 RA on their index date, the GLP-1 RA group was assigned based on the medication that had the most pharmacy encounters during that calendar year. Third, we further evaluated study groups 3 and 4, comparing GLP-1 RA users with no diabetes diagnosis vs individuals with diabetes (groups 1 and 2).

All analyses were performed using R 4.1.2 (R Foundation for Statistical Computing).

RESULTS

Overall, the initial data sample included 28,218,353 members in 2018 and decreased to 23,047,593 in 2023. GLP-1 RA users increased from 745 per 100,000 enrollees in 2018 to 3572 per 100,000 in 2023. Among GLP-1 RA users in the final study sample, the proportion of semaglutide users increased from 5.1% in 2018 to 63% in 2023 (Figure 1).

Meanwhile, from 2018 to 2023, the proportion of diabetic GLP-1 RA users decreased from 89% to 66%, respectively, and those without a diagnosis of diabetes (groups 3 and 4) tripled their share from 11% to 34% (Table 1). The proportion in group 3 increased from 4.5% to 17%, and the proportion in group 4 also increased to 17% (from 6.4%).

Figure 2 represents the trends in utilization of individual GLP-1 RA brand names by diabetes diagnosis and obesity/overweight status. There are different trends in prescribing GLP-1 RAs in individuals with and without a diabetes indication. Although all 3 semaglutide medications (Ozempic, Rybelsus, and Wegovy) exhibited growing trends compared with other GLP-1 RAs, the share of Ozempic increased 10-fold in both diabetic groups. For both nondiabetic groups (3 and 4), Wegovy had a more significant uptake compared with the diabetic groups. The second most common GLP-1 RA was dulaglutide (Trulicity) in both diabetic groups (1 and 2), which decreased its share from 46% (no obesity/overweight) and 43% (obesity/overweight) in 2018 to 26% and 14% in 2023, respectively, but remained the second most common medication in group 1 in 2023. We observed quite different trends and distributions of GLP-1 RAs among nondiabetic individuals. In both groups of nondiabetic GLP-1 RA users, either without obesity/overweight or with an obesity/overweight diagnosis, there was a decreasing trend from 2018 to 2023 in liraglutide (Saxenda) prescribing from 61% to 11% (without obesity/overweight) and 79% to 9.3% (with obesity/overweight). Dulaglutide prescribing equaled less than 10% of GLP-1 RA prescriptions among nondiabetic GLP-1 RA users during the study years.

Among group 3 (without diabetes and without obesity/overweight), there was a steady increase in off-label semaglutide (Ozempic) prescribing from 3.6% to 30%, and off-label semaglutide (Wegovy) increased to 38% drug share in 2023. Among group 4 (with obesity/overweight and without diabetes), liraglutide (Saxenda) dominated in 2018 with a share of 79%, but the share was sharply reduced to 9.3% in 2023. Ozempic users in this group increased from 2.7% in 2018 to 32% in 2022 (representing off-label prescribing as Ozempic is approved for patients with diabetes). However, the share was reduced to 19% in 2023, and semaglutide (Wegovy, approved for weight loss) dominated with 60% share.

Table 2 outlines the demographic differences between all 4 study groups. For groups 3 and 4, about 40% of users were younger than 45 years. This was significantly different from the 2 groups with diabetic enrollees, in which users younger than 45 years made up 12% and 18% in group 1 and group 2, respectively. GLP-1 RA users without diabetes were primarily women (~80%), whereas groups 1 and 2 were more evenly divided between women and men. Most GLP-1 RA users had commercial insurance compared with Medicare Advantage. When we evaluated demographic trends over the study years (eAppendix [available at ajmc.com]), there were minimal changes for each study group between 2018 and 2023. We identified that there was a noticeable increase in GLP-1 RA users younger than 45 years who had a diabetes diagnosis and were obese/overweight compared with the other study groups. The percentage of women in this group also increased from 54% in 2018 to 60% in 2023.

Finally, we investigated signs of potential premature prescribing of GLP-1 RAs among the study groups. On average, more than 300 days passed from the earliest diagnosis of diabetes (within the 365-day window before the index date) to the first GLP-1 RA prescription-filled date of the given year (groups 1 and 2). Less than 5% of diabetic GLP-1 RA users had their first diabetes diagnosis less than 30 days before being prescribed a GLP-1 RA across all study years. In groups 3 and 4 (no history of diabetes), there was an increase in prediabetes or abnormal glucose diagnosis from 18% to 22% over the study years. However, less than 9% of individuals had either a diabetes or prediabetes diagnosis within 90 days after starting a GLP-1 RA across the study years (Table 3).

DISCUSSION

GLP-1 RA prescribing increased significantly across the study years, especially for semaglutides, whereas dulaglutide, liraglutide, and exenatide decreased their share among GLP-1 RA users. Semaglutide, specifically Ozempic, usage increased 10-fold for all study groups between 2018 and 2022, but the proportion of Ozempic prescribing decreased in 2023 in the nondiabetic group. We observed an increasing trend in Wegovy prescribing in the nondiabetic groups, with a significant jump in proportion among the nondiabetic obese/overweight group to 60% in 2023. Other authors reported a similar decrease in dulaglutide prescription compared with Ozempic, with the potential explanation that semaglutide may be associated with better weight loss.¹⁸ In our study, we also observed a gradual decline in the percentage use of dulaglutide in all groups, with the share of dulaglutide prescribed in the nondiabetic group being lower to start. Another study reported an 11-fold increase in GLP-1 RA use between 2014 and 2022, with a growing proportion of GLP-1 RA users in the nondiabetic group.¹⁹ Conversely, Limonte et al reported that in the US, the uptake of GLP-1 RA medications among patients with diabetes remained low from 2017 to 2020. However, the authors pointed out that their results are derived from years in which clinical practice guidelines for GLP-1 RAs were emerging and might have impacted GLP-1 RA uptake. In addition, the slow uptake of these medications for diabetes treatment might be due to prohibitive cost (without coverage) and that the recommendations for type 2 diabetes during that period included an emphasis on lifestyle changes and other medications.²⁰

The nondiabetic groups had a vastly different pattern of GLP-1 RA prescribing compared with the diabetic groups. In 2018, 75% of these GLP-1 RA users were prescribed liraglutide (Saxenda), which is expected, given that it was the only GLP-1 RA approved by the FDA for weight loss.⁸ However, over the study years, the proportion of GLP-1 RA users prescribed liraglutide and other GLP-1 RAs decreased as semaglutide prescription increased. This finding is similar to those of previous research in which liraglutide was the primary medication prescribed for weight loss to those with no diabetes diagnosis.²¹ Liraglutide has several shortcomings compared with Ozempic, which was approved only for diabetes treatment, and Wegovy, which was approved for weight loss. Users are required to inject liraglutide daily and tend to achieve less weight loss; it also has a higher risk of adverse effects and lower cost-effectiveness than semaglutides.^21,22 Crabtree et al reported substantial hemoglobin A_1c (HbA_1c) and weight reductions in patients who switched to semaglutide from all other GLP-1 RAs and significant weight loss in those who switched from liraglutide, but not among those who switched from dulaglutide.²³

By evaluating the number of days between a fill date for a GLP-1 RA and a diabetes diagnosis, we found that only a small percentage were newly diagnosed with diabetes, and there was no significant increase in new diabetes or prediabetes diagnosis after the GLP-1 RA prescribing index date. Therefore, there is no convincing evidence from this study that providers reported additional diagnoses to increase the chance of medication approval for insurance coverage.

There was less off-label use of Ozempic in nondiabetic individuals (groups 3 and 4), and there was a shift to more Wegovy prescriptions in 2023 (off-label prescribing in group 3). Wegovy is associated with higher treatment costs than Ozempic. However, Wegovy may be more effective for weight loss as it is usually prescribed in slightly higher doses than Ozempic. It is critical for managed care systems to know whether switching to more effective GLP-1 RAs (eg, semaglutide vs liraglutide) reduces obesity rates and consequently reduces obesity-related chronic disease progression; further assessment is needed to address this knowledge gap. Increasing trends in prescribing semaglutide may lead to a reduction in rates of obesity in individuals with and without diabetes, better management of diabetes, and a reduction in morbidity and mortality of cardiovascular diseases. More studies using real-world data are needed to assess the long-term consequences of recently FDA-approved GLP-1 RAs.

To ensure weight management effectiveness and return on investment in GLP-1 RAs, medications need to be taken long term as a lifelong treatment. Adherence to GLP-1 RA treatment is one of the significant concerns, partially due to the adverse effects and high costs. More than half of users of anti-obesity medications discontinue them within 6 months, with variation by medication type and dosage,^12,24-26 with higher risk of discontinuation in individuals without diabetes, if medication is not covered by insurance, or if there was loss of coverage during treatment. Discontinuation of GLP-1 RAs is associated with a potentially significant return of weight,²⁶ reduced muscle mass, and poorer obesity-related outcomes in the long term.One consideration to counter these consequences is to lower the costs of these medications, which will increase access to this treatment, noting that the cost-effectiveness threshold for semaglutide is $7500 to $9800 per year.²⁷ In clinical trials, GLP-1 RAs showed greater effectiveness than other diabetic medications such as metformin for weight loss, glycemic control, and reducing cardiovascular events in patients with type 2 diabetes.^28,29 Semaglutide is superior to other GLP-1 RAs in weight loss, and using GLP-1 RAs long term will maintain weight loss more effectively than other interventions.³⁰ In diabetic patients with normal weight, semaglutide showed a better reduction in HbA_1c levels compared with those with an obesity/overweight diagnosis.²⁸ In the current standards of diabetic care, GLP-1 RAs such as Ozempic are recommended as the second line of treatment for diabetes or the first-line treatment for diabetes in combination with other medications for severe cases or patients at high risk for cardiovascular complications.³¹ Although semaglutide is on formularies for weight loss treatment, prior authorization or prior trial of alternative treatments, such as lifestyle management program participation, is often required. Therefore, the majority of patients must pay out of pocket for weight loss treatment, which reduces access to this type of treatment. The observing trend shows that more individuals were able to access Wegovy after the FDA approved it for weight loss, and there is less off-label prescribing of Ozempic for nondiabetic patients, as managed care organizations and other payers implement coverage restrictions to ensure appropriate use within approved populations.

There are a few considerations when assessing the return on investment in GLP-1 RA treatment. When evaluating the number needed to treat to lower risk of cardiovascular events among patients with diabetes, a substantially lower number needed to treat over 6 years compared with 1 year was observed,³² suggesting that the cardiovascular benefits of GLP-1 RAs in patients with diabetes become more pronounced with long-term use; however, further evaluation of cardiovascular benefits and sustainability of lifelong use of these medications in patients with obesity is needed. Other considerations include potential additional health benefits (recent studies showed a reduction in C-reactive protein and inflammation^33,34), target population selection, and long-term adverse effects. Another issue to consider is how providers’ behavior may change in treating obese/overweight patients over time. There is a risk that effective lifestyle weight loss treatment will be underutilized due to the faster transition to pharmacologic intervention. From a patient perspective, it is important to consider whether this approach might diminish motivation to adopt lifestyle changes fully. Additionally, there may be unique benefits for older adults who have difficulty increasing their physical activity due to chronic conditions and health limitations. Future studies are needed to answer these questions by assessing the long-term effectiveness of GLP-1 RA prescribing and evaluating the cost-effectiveness of GLP-1 RA prescribing in various target populations.

Limitations

The major limitation of this study is that trends were evaluated for medications that were covered by private insurance, which lacks data for Medicare fee-for-service. As Medicare does not cover GLP-1 RAs for weight loss, there is a potential underestimation of GLP-1 RA prescribing in the Medicare population.

It may be argued that obesity and weight are underreported in claims data.³⁵ However, a recent study concluded that obesity-related diagnosis codes accurately identified patients with obesity in epidemiological studies using claims data.³⁶ Additionally, it is assumed that if a GLP-1 RA were prescribed for obesity, the prescribing physician would likely document the diagnosis, thus limiting the potential for underreporting. This study utilized a large, national, representative sample of working-aged adults and Medicare Advantage plan beneficiaries. However, this may limit the generalizability of the results because this study includes only commercially insured individuals. Utilizing claims data allowed us to avoid recall bias. We can capture medications prescribed and filled by the patient, but we cannot access actual GLP-1 RA utilization when paid for out of pocket. For medicines such as tirzepatide, we could not conduct a comprehensive trend analysis due to the limited time these medications were on the market and the availability of the data. More research is needed to evaluate the prescribing patterns of these new GLP-1 RAs.

CONCLUSIONS

We identified a prominent increase in GLP-1 RA prescribing between 2018 and 2023 in all study groups among individuals commercially insured in the US. The GLP-1 RA prescribing patterns in groups with and without diabetes were significantly different. In contrast, prescribing patterns between obese/overweight and non–obese/overweight groups were relatively similar regardless of whether the enrollee had a diabetes diagnosis. We found that the proportion of users with diabetes slightly increased, but the proportion of users with obese/overweight diagnoses increased significantly from 2018 to 2023. Similarly, there was a significant increase in semaglutide prescriptions among all GLP-1 RA users, whereas the proportion of other GLP-1 RAs decreased over study years to varying degrees. Accessibility, especially cost, will be a critical factor in patients’ usage of these new medications.

Author Affiliations: UTHealth Houston School of Public Health, Center for Health Care Data (MU, JSW, CNT, LG, TMK), Houston, TX.

Source of Funding: None.

Author Disclosures: The authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (MU, CNT, LG, TMK); acquisition of data (JSW, TMK); analysis and interpretation of data (MU, JSW, CNT, LG, TMK); drafting of the manuscript (MU, JSW, CNT, TMK); critical revision of the manuscript for important intellectual content (MU, JSW, CNT, TMK); statistical analysis (MU, JSW, LG, TMK); administrative, technical, or logistic support (CNT, TMK); and supervision (TMK).

Address Correspondence to: Maria Ukhanova, MD, PhD, UTHealth Houston School of Public Health, Center for Health Care Data, 1200 Pressler St, Houston, TX 77030. Email: maria.ukhanova.1@uth.tmc.edu.

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