ABSTRACT
Objective
This study aimed to characterize the reasons for treatment discontinuation with injectable semaglutide or tirzepatide for obesity in regular clinical practice.
Methods
This cross‐sectional study used electronic health record data between January 2022 and December 2024 from a single integrated health system in Ohio and Florida. The primary reason for treatment discontinuation was examined in a randomly selected sample of adults with overweight or obesity and without type 2 diabetes who initiated injectable semaglutide or tirzepatide and discontinued treatment within the first year.
Results
We randomly selected 288 patients; 145 received semaglutide and 143 tirzepatide. Overall, 137 patients (47.6%) discontinued their medication due to cost or insurance‐related issues, 42 (14.6%) due to inability to tolerate the side effects, 34 (11.8%) as they were unable to fill the medication due to shortages, 7 (2.4%) as they switched to a compounded medication, and 5 (1.7%) due to unsatisfactory weight loss; 31 (10.8%) discontinued for other reasons, and for 32 (11.1%) patients the discontinuation reason was not specified in the electronic health record.
Conclusions
High cost or insurance‐related issues are the most common reasons for treatment discontinuation with semaglutide or tirzepatide for obesity. Our findings highlight the need for policies to address cost and could inform discussions between healthcare providers and patients concerning cost and side effects.
Keywords: glucagon‐like peptide‐1 receptor agonists, obesity pharmacotherapy, treatment discontinuation
Study Importance.
- What is already known?
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○Although treatment discontinuation is common among patients receiving tirzepatide or semaglutide for obesity, data quantifying specific reasons for discontinuation, including by discontinuation timing, remain limited.
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- What does this study add?
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○In this randomly selected sample of 288 patients who discontinued obesity pharmacotherapy with injectable semaglutide or tirzepatide within the first year of treatment initiation, the most common reasons for discontinuation were cost or insurance‐related issues (47.6%), inability to tolerate the side effects (14.6%), and medication shortages (11.8%).
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○Cost or insurance‐related barriers were the most common reason for discontinuation at all time points; however, patients discontinuing due to cost were more likely to do so later in treatment, whereas those discontinuing due to side effects tended to do so earlier.
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- How might these results change the direction of research or the focus of clinical practice?
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○Our findings highlight the need for policy interventions to address those factors and could inform discussions between healthcare providers and patients around challenges with obesity pharmacotherapy.
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1. Introduction
Overweight and obesity are common conditions that increase the risk of developing major health complications, such as type 2 diabetes (T2D), cardiovascular disease, certain cancers, osteoarthritis, and obstructive sleep apnea [1, 2]. The past few years have witnessed significant progress in the development of obesity medications, specifically long‐acting glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) semaglutide and glucose‐dependent insulinotropic polypeptide (GIP) and GLP‐1 dual receptor agonist tirzepatide. These medications produce greater weight loss than obesity medications previously approved by the Food and Drug Administration (FDA), with randomized trials demonstrating body weight reductions of 15%–21% in patients with overweight or obesity and without T2D [3, 4, 5]. Treatment with semaglutide also prevents cardiovascular events, particularly in those with obesity and established atherosclerotic cardiovascular disease [6].
As in the case of other chronic diseases, obesity medication discontinuation attenuates health benefits and prompts weight regain in most individuals [7, 8, 9]. For example, in the STEP 1 trial extension study, patients on average regained two‐thirds of their lost weight, and cardiometabolic improvements reversed following the discontinuation of semaglutide and lifestyle intervention [8]. Similarly, discontinuation of tirzepatide resulted in a substantial regain of lost weight in the SURMOUNT‐4 trial, with only 17% of the participants maintaining at least 80% of the weight loss achieved [7].
Discontinuation of these highly effective obesity medications is common in clinical practice in the United States [9, 10, 11, 12, 13]. Although potential causes of this (such as cost and insurance‐related issues, medication shortages, and side effects) have been speculated by clinicians and third‐party payers, no US‐based study to date has quantified the reasons for it. Such understanding could help in addressing the barriers to continued use of these medications. We aimed to characterize the reasons for early (within < 3 months of treatment initiation) and late (within 3–12 months) discontinuation of injectable semaglutide or tirzepatide for obesity in clinical practice. We hypothesized that the reasons for discontinuation would vary by timing (early vs. late discontinuation).
2. Methods
2.1. Study Design and Setting
Data for this cross‐sectional study were obtained from the Cleveland Clinic electronic health record (EHR) in Ohio and Florida, including linked Surescripts pharmacy dispensation records [14], from January 1, 2022, to December 31, 2024. The Surescripts prescription data service captures prescriptions paid for through insurance benefits, cash, coupons, or other methods from nearly all major pharmacies and pharmacy benefit managers in the United States [15].
This study was approved by the Cleveland Clinic Institutional Review Board as minimal‐risk research using data collected for routine clinical practice, for which the requirement for informed consent was waived. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines were followed.
2.2. Study Participants
We identified adult patients (aged ≥ 18 years) who (1) had an initial fill for injectable semaglutide or tirzepatide for obesity from January 1, 2022, to December 31, 2023, (2) had a body mass index (BMI; calculated as the weight in kilograms divided by the height in meters squared) of at least 30.0, recorded on the date of treatment initiation (index date) or during the latest available primary care visit before the index date, or a BMI of at least 27.0 and one or more weight‐related comorbidities (i.e., hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease, including coronary artery disease, atrial fibrillation, heart failure, and stroke), (3) did not have T2D at baseline or undergo bariatric surgery within 2 years before the index date, and (4) discontinued obesity pharmacotherapy within the first year of treatment. To ensure that these were initial fills, we required that they be preceded by at least 6 months without fills of any FDA‐approved obesity medication, including semaglutide, liraglutide, tirzepatide, phentermine‐topiramate, naltrexone‐bupropion, phentermine, or orlistat. The presence of T2D was defined by either an HbA1c level of at least 6.5% or the presence of a diagnostic code for T2D (International Classification of Diseases, Ninth Revision, code 250.X0 or 250.X2 or International Statistical Classification of Diseases, Tenth Revision, code E11.X). Discontinuation of obesity pharmacotherapy at 1 year was defined as a gap of greater than 90 days between exhaustion of the previous supply and next dispense or between exhaustion of the last supply and end of study follow‐up [16]. Patients who switched between injectable forms of semaglutide, tirzepatide, or other antiobesity agents (including semaglutide, tirzepatide, liraglutide, phentermine‐topiramate, naltrexone‐bupropion, orlistat, phentermine, metformin, topiramate, bupropion, pramlintide, zonisamide, and dulaglutide) but had a gap of less than 90 days were not considered to have discontinued obesity pharmacotherapy. We grouped patients who discontinued pharmacotherapy into those who discontinued early (< 3 months of the index date) and late (from 3 to 12 months). We chose the 3‐month mark since it has been commonly used by clinicians, researchers, and third‐party payers to assess early response to obesity medications and, if such response is not satisfactory, alter the therapy [17, 18, 19]. This study captured injectable semaglutide and tirzepatide under the brand names approved by the FDA for obesity (Wegovy and Zepbound), as well as the off‐label use of those approved for T2D (Ozempic and Mounjaro) [20], including all starting and maintenance doses.
From the pool of individuals who met the aforementioned criteria, we randomly selected 300 patients whose initial obesity medication prescription was placed by a Cleveland Clinic provider and the last medication fill before treatment discontinuation was either semaglutide or tirzepatide, and we conducted manual chart reviews to determine the primary reason for discontinuation. This number was predetermined based on the feasibility of study aims. We examined the earliest occurrence of medication discontinuation within the first year of treatment. The random sampling was balanced in terms of obesity medication (semaglutide, tirzepatide) and discontinuation timing (early, late); we also oversampled men. This was done to optimize our study power and to make sure all key groups were adequately represented.
2.3. Content Analysis
Three independent reviewers with relevant experience conducted manual chart reviews to identify the reasons for treatment discontinuation, including any reported medication side effects. They reviewed provider notes, documentation of insurance prior authorization approvals or denials, and pharmacy and MyChart messages, as well as phone encounter summaries. Content analysis allows for the analysis of communications, messages, or content, in which inferences are made based on context [21]. Therefore, we used it to categorize the primary reason for treatment discontinuation for each patient.
Our coding system included predefined categories based on available literature and consultations with prescribers [11, 12, 13]; we also examined the data to assure that there are no additional salient categories. We grouped treatment discontinuation reasons into the following categories: (1) cost or insurance‐related (including insurance denial, expiration of manufacturer discount coupon, or out‐of‐pocket cost being unaffordable), (2) medication shortages, (3) side effects, (4) switching to a compounded medication, (5) unsatisfactory weight loss, (6) other, and (7) unspecified. Table S1 provides examples of how textual data were categorized.
At the onset of chart reviews, we measured inter‐rater reliability via Randolph's free‐marginal multirater kappa, which met our prespecified requirement of ĸ > 0.75, indicating an “excellent” level of agreement [22]. Subsequently, the reviewers and the study's first author held regular meetings to cross‐check the coding approach and reconcile any cases where the assigned coder had questions. Additional validity checks included periodically verifying the extracted textual data against the selected codes and independently reviewing 20% of the charts.
2.4. Other Variables
We also extracted sociodemographic and clinical variables from the EHR to describe our study cohort. Age, sex, race, ethnicity, primary payer type, and area deprivation index (ADI) based on census block group neighborhood‐level data [23] were recorded from the primary care visit closest to the index date. Sex, race, and ethnicity were based on self‐report using fixed categories. Race was categorized into Black, White, and other groups (including American Indian or Alaska Native, Asian, multiracial, Native Hawaiian or other Pacific Islander, and other). Ethnicity included Hispanic and non‐Hispanic. ADI percentiles were based on a nationwide ranking from 1 to 100, where an ADI with a ranking of 1 indicates the lowest level of disadvantage [23]. Payer type was categorized as private, Medicare, Medicaid, and self‐pay/other. Baseline body weight, BMI, and age‐adjusted Charlson Comorbidity Index were also captured from the EHR [24].
2.5. Statistical Analysis
A descriptive analysis was performed to summarize the primary reasons for semaglutide and tirzepatide discontinuation, stratified by the timing of pharmacotherapy discontinuation. We also conducted exploratory analyses of discontinuation primary reason stratified by payer type, year of treatment initiation, and index medication. Pearson χ 2 test and Fisher's exact test were used for standard group comparisons [25]. All statistical testing was two‐tailed with α = 0.05 used to determine statistical significance. All analyses were conducted in R, version 4.4.0 (R Program for Statistical Computing).
To assess the robustness of our data on the primary reasons for semaglutide and tirzepatide discontinuation, we examined how much the results changed when progressing from the first 50% of the charts reviewed to 75% and 100%, respectively.
3. Results
A total of 8184 individuals with obesity or overweight (and one or more weight‐related comorbidities) and without T2D initiated obesity pharmacotherapy with a prescription fill for injectable semaglutide or tirzepatide from January 1, 2022, to December 31, 2023. Of those, 54.9% (4492) discontinued their medication within the first year (Figure 1). Characteristics of those who did and did not discontinue their medication within the first year of treatment initiation are presented in Table S2.
FIGURE 1.
Identification of eligible patients for inclusion. [Color figure can be viewed at wileyonlinelibrary.com]
Out of the 300 randomly selected patients who were identified to have discontinued their treatment based on Surescripts data, 1 was excluded because pharmacotherapy initiation occurred in 2021; 11 were excluded because they were still taking the medications of interest based on a progress note or patient MyChart message in the EHR (Figure 1). Our analytic sample included 288 patients who filled an initial prescription for injectable semaglutide (145) or tirzepatide (143) from January 1, 2022, to December 31, 2023, and discontinued the therapy within the first year. Mean (SD) age was 52.1 (13.3) years, baseline weight was 116.1 (28.5) kg, and baseline BMI was 39.7 (7.9). A total of 179 patients (62.2%) were female and 109 (37.8%) were male; 41 (14.2%) were Black, 223 (77.4%) were White, and 15 (5.2%) were of other race; 21 (7.3%) had Hispanic ethnicity. Most patients were privately insured (221 [76.7%]); 41 (14.2%) had Medicare, 17 (5.9%) Medicaid, and 9 (3.1%) were self‐paying or had other insurance. The median ADI was 56.0 (interquartile range [IQR]: 33.0–71.0). The median age‐adjusted Charlson Comorbidity Index was 2.0 (IQR: 1.0–4.0) (Table 1).
TABLE 1.
Characteristics of patients who discontinued treatment with injectable semaglutide or tirzepatide for obesity, N = 288.
| Characteristic | Overall (N = 288) | Semaglutide (n = 145) | Tirzepatide (n = 143) |
|---|---|---|---|
| Age, mean (SD), years | 52.1 (13.3) | 53.0 (13.6) | 51.1 (13.0) |
| Sex | |||
| Male | 109 (37.8%) | 53 (36.6%) | 56 (39.2%) |
| Female | 179 (62.2%) | 92 (63.4%) | 87 (60.8%) |
| Race | |||
| Black | 41 (14.2%) | 25 (17.2%) | 16 (11.2%) |
| Other a | 15 (5.2%) | 8 (5.5%) | 7 (4.9%) |
| White | 223 (77.4%) | 108 (74.5%) | 115 (80.4%) |
| Not reported | 9 (3.1%) | 4 (2.8%) | 5 (3.5%) |
| Ethnicity | |||
| Hispanic | 21 (7.3%) | 14 (9.7%) | 7 (4.9%) |
| Non‐Hispanic | 255 (88.5%) | 127 (87.6%) | 128 (89.5%) |
| Not reported | 12 (4.2%) | 4 (2.8%) | 8 (5.6%) |
| Primary payer | |||
| Private | 221 (76.7%) | 113 (77.9%) | 108 (75.5%) |
| Medicare | 41 (14.2%) | 21 (14.5%) | 20 (14.0%) |
| Medicaid | 17 (5.9%) | 8 (5.5%) | 9 (6.3%) |
| Self‐pay/other | 9 (3.1%) | 3 (2.1%) | 6 (4.2%) |
| ADI, median (IQR) b | 56.0 (33.0, 71.0) | 55.0 (34.0, 70.0) | 57.5 (32.0, 71.0) |
| Unknown | 3 (1.0) | 2 (1.4) | 1 (0.7) |
| Baseline weight, kg, mean (SD) | 116.1 (28.5) | 112.7 (25.9) | 119.4 (30.7) |
| Baseline BMI, mean (SD) | 39.7 (7.9) | 39.0 (6.5) | 40.4 (9.1) |
| Charlson Comorbidity Index, median (IQR) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) | 2.0 (1.0, 4.0) |
| Obesity pharmacotherapy discontinuation status c | |||
| Early | 138 (47.9%) | 70 (48.3%) | 68 (47.6%) |
| Late | 150 (52.1%) | 75 (51.7%) | 75 (52.4%) |
| Number of obesity medications trialed d , median (IQR) | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) | 1.0 (1.0, 2.0) |
| Year of treatment initiation | |||
| 2022 | 100 (34.7%) | 30 (20.7%) | 70 (49.0%) |
| 2023 | 188 (65.3%) | 115 (79.3%) | 73 (51.0%) |
Abbreviation: ADI, area deprivation index.
Other race included American Indian or Alaska Native, Asian, multiracial, Pacific Islander, and other.
ADI percentiles were based on a nationwide ranking from 1 to 100, where an ADI with a ranking of 1 indicates the lowest level of disadvantage.
Discontinuation of obesity pharmacotherapy at 1 year was defined as a gap of greater than 90 days between exhaustion of previous supply and next dispense or between exhaustion of last supply and end of study follow‐up. Patients who switched between injectable forms of semaglutide, tirzepatide, or other antiobesity agents but had a gap of less than 90 days were not considered to have discontinued their obesity pharmacotherapy. We grouped patients who discontinued obesity pharmacotherapy into those who discontinued early (< 3 months of the index date) and late (from 3 to 12 months of the index date).
Including semaglutide, tirzepatide, liraglutide, phentermine‐topiramate, naltrexone‐bupropion, orlistat, phentermine, metformin, topiramate, bupropion, pramlintide, zonisamide, and dulaglutide.
Within the sample, 137 patients (47.6%) discontinued their medication due to cost or insurance‐related issues (including insurance denial, expiration of manufacturer discount coupon, or out‐of‐pocket cost being unaffordable), 42 (14.6%) due to side effects, 34 (11.8%) due to medication shortages, 7 (2.4%) due to switching to a compounded medication, and 5 (1.7%) due to unsatisfactory weight loss; 31 (10.8%) discontinued for other reasons, and 32 (11.1%) patients had no reason specified in the EHR. Among those who discontinued the treatment due to side effects (n = 42), the most commonly reported side effects included nausea (13), abdominal pain (8), vomiting (7), diarrhea (6), and (worsening) depression (4). Other reasons included other health events unrelated to the treatment course (9), hesitancy about the treatment (5), pharmacotherapy being part of bariatric preoperative preparation (4), treatment being paused/stopped after achieving desired body weight (4), communication issues related to required documentation (4), medication hold due to surgical procedure (2), other personal reasons (2), and patients no longer meeting the BMI criteria for obesity pharmacotherapy (1).
As shown in Table 2, discontinuation due to cost or insurance‐related issues was more common in patients who discontinued late compared to those who did early (54.0% vs. 40.6%, p = 0.02). Conversely, discontinuation due to intolerance to side effects was more prevalent in those who discontinued early vs. late (21.0% vs. 8.7%, p = 0.003). As shown in Table 3, discontinuation due to cost or insurance‐related issues was also more common in patients with Medicare or Medicaid coverage compared to those with private payer (61.0%, 76.5%, and 43.0%, respectively, p = 0.01). The distribution of treatment discontinuation reasons did not significantly differ by treatment initiation year (2022 vs. 2023) or index medication (semaglutide vs. tirzepatide) (Tables S3 and S4). The results of the sensitivity analysis supported our main findings (Table S5).
TABLE 2.
Reasons for obesity pharmacotherapy discontinuation by discontinuation timing, N = 288.
| Discontinuation reason | Overall (N = 288) | Early a (n = 138) | Late a (n = 150) | p b |
|---|---|---|---|---|
| Cost or insurance‐related c | 137 (47.6%) | 56 (40.6%) | 81 (54.0%) | 0.02 |
| Medication shortages | 34 (11.8%) | 15 (10.9%) | 19 (12.7%) | 0.6 |
| Side effects | 42 (14.6%) | 29 (21.0%) | 13 (8.7%) | 0.003 |
| Switch to a compounded medication | 7 (2.4%) | 4 (2.9%) | 3 (2.0%) | 0.7 |
| Unsatisfactory weight loss | 5 (1.7%) | 2 (1.4%) | 3 (2.0%) | > 0.9 |
| Other | 31 (10.8%) | 19 (13.8%) | 12 (8.0%) | 0.1 |
| Unspecified | 32 (11.1%) | 13 (9.4%) | 19 (12.7%) | 0.4 |
Discontinuation of obesity pharmacotherapy at 1 year was defined as a gap of greater than 90 days between exhaustion of previous supply and next dispense or between exhaustion of last supply and end of study follow‐up. Patients who switched between injectable forms of semaglutide, tirzepatide, or other antiobesity agents but had a gap of less than 90 days were not considered to have discontinued their obesity pharmacotherapy. We grouped patients who discontinued obesity pharmacotherapy into those who discontinued early (< 3 months of the index date) and late (from 3 to 12 months of the index date).
Based on Pearson χ 2 test or Fisher's exact test.
Including insurance denial, expiration of manufacturer discount coupon, or out‐of‐pocket cost being unaffordable.
TABLE 3.
Reasons for obesity pharmacotherapy discontinuation by payer type, N = 288.
| Discontinuation reason | Overall (N = 288) | Medicaid (n = 17) | Medicare (n = 41) | Private (n = 221) | Self‐pay/other (n = 9) | p a |
|---|---|---|---|---|---|---|
| Cost or insurance‐related b | 137 (47.6%) | 13 (76.5%) | 25 (61.0%) | 95 (43.0%) | 4 (44.4%) | 0.01 |
| Medication shortages | 34 (11.8%) | 0 (0.0%) | 1 (2.4%) | 33 (14.9%) | 0 (0.0%) | 0.03 |
| Side effects | 42 (14.6%) | 0 (0.0%) | 5 (12.2%) | 35 (15.8%) | 2 (22.2%) | 0.2 |
| Switch to a compounded medication | 7 (2.4%) | 0 (0.0%) | 1 (2.4%) | 6 (2.7%) | 0 (0.0%) | > 0.9 |
| Unsatisfactory weight loss | 5 (1.7%) | 0 (0.0%) | 2 (4.9%) | 3 (1.4%) | 0 (0.0%) | 0.4 |
| Other | 31 (10.8%) | 1 (5.9%) | 4 (9.8%) | 25 (11.3%) | 1 (11.1%) | > 0.9 |
| Unspecified | 32 (11.1%) | 3 (17.6%) | 3 (7.3%) | 24 (10.9%) | 2 (22.2%) | 0.4 |
Based on Fisher's exact test.
Including insurance denial, expiration of manufacturer discount coupon, or out‐of‐pocket cost being unaffordable.
4. Discussion
In this randomly selected sample of 288 patients who discontinued obesity pharmacotherapy with injectable semaglutide or tirzepatide within the first year of treatment, the most common reasons for discontinuation were cost or insurance‐related barriers (48%), side effects (15%), and medication shortages (12%). Cost or insurance‐related barriers were the most common reason for discontinuation at all time points; however, patients discontinuing due to cost were more likely to do so later in treatment, whereas those discontinuing due to side effects tended to do so earlier. Patients with Medicare or Medicaid coverage had higher rates of discontinuation due to cost or insurance‐related barriers. Currently, most state Medicaid programs, including the Medicaid programs in Ohio and Florida, as well as Medicare Part D prescription drug plans, do not offer coverage for obesity medications [26].
Although emerging data indicate discontinuation with these medications is common [9, 10, 12, 13, 27], to our knowledge, this is the first US study to quantify the specific reasons for discontinuation in clinical practice. Previous studies have examined the association of insurance type, copayment amount, and socio‐economic factors with the initiation and persistence of novel obesity medications [11, 12, 28, 29]. A recent study reported side effects, logistical challenges, medication cost, supply shortages, and dissatisfaction with weight loss as the primary reasons for GLP‐1 RA medication (primarily semaglutide and liraglutide) discontinuation among patients treated at specialized obesity clinics in Ireland [30]. Discontinuation due to factors typically irrelevant in clinical trial settings (i.e., cost or insurance‐related issues and medication shortages) could contribute to the substantial discrepancy between discontinuation rates at ~1 year in pivotal Phase 3 trials (e.g., 17% for 2.4‐mg semaglutide in STEP 1 [3] and 14%–16% for tirzepatide 5–15 mg in SURMOUNT‐1 [4]) and those reported in real‐world studies (where discontinuation rates range 50%–65%, depending on the population, medication combinations of, and timeframe analyzed) [9, 10, 11, 13].
Our findings have important clinical and policy implications. Third‐party payers cite high discontinuation rates as a key rationale for restricting insurance coverage for obesity medications [31]. However, our findings indicate that high costs, often imposed by the insurance companies themselves, and medication shortages significantly contribute to treatment discontinuation. Although medication shortages have improved, insurance barriers remain. This highlights the need for a more nuanced insurance benefit design that relies on evidence‐based management tools, rather than simply limiting or denying pharmacotherapy coverage for obesity [32, 33]. In addition, manufacturers should evaluate the long‐term impact of time‐limited savings programs and discount coupons. Finally, recognizing the primary reasons for discontinuation may facilitate more informed discussions between healthcare providers and their patients, helping to address challenges in long‐term persistence with these highly effective medications.
Strengths of this study include its randomly selected, balanced, and contemporaneous sample, integration of prescription dispensation data from Surescripts with clinical information [14, 15], and use of rich data sources, including provider notes, insurance prior authorization approvals or denials, pharmacy and MyChart messages, and phone encounters to ascertain reasons for treatment discontinuation. This study also has limitations. We included adult patients from Ohio and Florida in a single large integrated health system. Patient characteristics and healthcare delivery patterns vary across the United States, which may limit the generalizability of our findings. For 11% of our sample, the discontinuation reason was not specified in the EHR, and some of those patients could have had one of the discontinuation reasons identified in this study. Although we captured the primary reason for discontinuation for each patient, some individuals could have had other contributing factors for discontinuing the treatment. Furthermore, although coupon expiration was among the commonly noted reasons for medication discontinuation, we do not know how many patients who received coupons persisted with their medications. Coupons for these medications varied in their duration during the study period, and those expiring within ≥ 12 months of treatment initiation would have fallen outside of the study follow‐up, limiting our ability to fully capture the impact of coupon expiration. Future studies should address the benefits and harms of time‐limited coupons, which could harm patients who experience substantial weight loss and then regain, also known as weight‐cycling [34, 35].
5. Conclusion
In this cross‐sectional study of 288 patients who discontinued obesity pharmacotherapy with injectable semaglutide or tirzepatide within the first year, nearly half discontinued therapy due to high cost or insurance‐related barriers, whereas side effects (15%) and medication shortages (12%) were also common reasons for discontinuation. Discontinuation due to cost or insurance‐related issues was more prevalent beyond 3 months, whereas side effects typically led to earlier discontinuation. Our findings highlight the need for targeted interventions to mitigate these factors.
Conflicts of Interest
Dr. Butsch reported advisory board fees from Novo Nordisk A/S, Eli Lilly and Co., Boehringer Ingelheim, and Abbott and research funding from Eli Lilly and Co. outside the submitted work. Dr. Rothberg reported receiving consulting fees from the Blue Cross Blue Shield Association outside the submitted work. Other authors declare no conflicts of interest.
Supporting information
Data S1: oby70058‐sup‐0001‐Supinfo.docx.
Table S1: Examples of how extracted textual data were categorized.
Table S2: Characteristics of patients who did and did not discontinued treatment with semaglutide or tirzepatide for obesity at 1 year, N = 8184.
Table S3: Reasons for obesity pharmacotherapy discontinuation by year of treatment initiation, N = 288.
Table S4: Reasons for obesity pharmacotherapy discontinuation by index medication, N = 288.
Table S5: Results of the sensitivity analysis.
Gasoyan H., Butsch W. S., Casacchia N. J., et al., “Reasons for Discontinuation of Obesity Pharmacotherapy With Semaglutide or Tirzepatide in Clinical Practice,” Obesity 33, no. 12 (2025): 2296–2303, 10.1002/oby.70058.
Funding: This work was supported by the Cleveland Clinic Research Program Committees (grant/award number: RPC8755).
Data Availability Statement
The dataset generated during the current study is not publicly available to preserve patient confidentiality. However, the dataset is available from the corresponding author to academic investigators following receipt of a signed data‐sharing agreement and after reviewing the study protocol (approved by a local institutional review board or research ethics committee), statistical analysis plan, and publication plan. The Cleveland Clinic Institutional Review Board and the Law Department must approve the request before sharing the deidentified data. The corresponding author will respond to these requests within 2 months of receipt.
References
- 1. Adult Obesity Prevalence Maps, Centers for Disease Control and Prevention , accessed October 28, 2024, https://www.cdc.gov/obesity/data‐and‐statistics/adult‐obesity‐prevalence‐maps.html.
- 2. Guh D. P., Zhang W., Bansback N., Amarsi Z., Birmingham C. L., and Anis A. H., “The Incidence of Co‐Morbidities Related to Obesity and Overweight: A Systematic Review and Meta‐Analysis,” BMC Public Health 9, no. 1 (2009): 88, 10.1186/1471-2458-9-88. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Wilding J. P. H., Batterham R. L., Calanna S., et al., “Once‐Weekly Semaglutide in Adults With Overweight or Obesity,” New England Journal of Medicine 384, no. 11 (2021): 989–1002, 10.1056/NEJMoa2032183. [DOI] [PubMed] [Google Scholar]
- 4. Jastreboff A. M., Aronne L. J., Ahmad N. N., et al., “Tirzepatide Once Weekly for the Treatment of Obesity,” New England Journal of Medicine 387, no. 3 (2022): 205–216, 10.1056/NEJMoa2206038. [DOI] [PubMed] [Google Scholar]
- 5. Gudzune K. A. and Kushner R. F., “Medications for Obesity: A Review,” JAMA 332, no. 7 (2024): 571–584, 10.1001/jama.2024.10816. [DOI] [PubMed] [Google Scholar]
- 6. Lincoff A. M., Brown‐Frandsen K., Colhoun H. M., et al., “Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes,” New England Journal of Medicine 389, no. 24 (2023): 2221–2232, 10.1056/NEJMoa2307563. [DOI] [PubMed] [Google Scholar]
- 7. Aronne L. J., Sattar N., Horn D. B., et al., “Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT‐4 Randomized Clinical Trial,” JAMA 331, no. 1 (2024): 38–48, 10.1001/jama.2023.24945. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Wilding J. P. H., Batterham R. L., Davies M., et al., “Weight Regain and Cardiometabolic Effects After Withdrawal of Semaglutide: The step 1 Trial Extension,” Diabetes, Obesity & Metabolism 24, no. 8 (2022): 1553–1564, 10.1111/dom.14725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Gasoyan H., Butsch W. S., Schulte R., et al., “Changes in Weight and Glycemic Control Following Obesity Treatment With Semaglutide or Tirzepatide by Discontinuation Status,” Obesity 33 (2025): 1657–1667, 10.1002/oby.24331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Gasoyan H., Pfoh E. R., Schulte R., Le P., Butsch W. S., and Rothberg M. B., “One‐Year Weight Reduction With Semaglutide or Liraglutide in Clinical Practice,” JAMA Network Open 7, no. 9 (2024): e2433326, 10.1001/jamanetworkopen.2024.33326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Do D., Lee T., Peasah S. K., Good C. B., Inneh A., and Patel U., “GLP‐1 Receptor Agonist Discontinuation Among Patients With Obesity and/or Type 2 Diabetes,” JAMA Network Open 7, no. 5 (2024): e2413172, 10.1001/jamanetworkopen.2024.13172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Gasoyan H., Pfoh E. R., Schulte R., Le P., and Rothberg M. B., “Early‐ and Later‐Stage Persistence With Antiobesity Medications: A Retrospective Cohort Study,” Obesity 32, no. 3 (2024): 486–493, 10.1002/oby.23952. [DOI] [PubMed] [Google Scholar]
- 13. Rodriguez P. J., Zhang V., Gratzl S., et al., “Discontinuation and Reinitiation of Dual‐Labeled GLP‐1 Receptor Agonists Among US Adults With Overweight or Obesity,” JAMA Network Open 8, no. 1 (2025): e2457349, 10.1001/jamanetworkopen.2024.57349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Blecker S., Adhikari S., Zhang H., et al., “Validation of EHR Medication Fill Data Obtained Through Electronic Linkage With Pharmacies,” Journal of Managed Care & Specialty Pharmacy 27, no. 10 (2021): 1482–1487, 10.18553/jmcp.2021.27.10.1482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Surescripts , “Surescripts Dispensed Prescription Data Service Now Covers Nearly 240 Million Patients to Advance Population Health,” press release, May 22, 2017, https://surescripts.com/news‐center/press‐releases/detail/surescripts‐dispensed‐prescription‐data‐service‐now‐covers‐nearly‐240‐million‐patients‐to‐advance‐population‐health.
- 16. Raebel M. A., Schmittdiel J., Karter A. J., Konieczny J. L., and Steiner J. F., “Standardizing Terminology and Definitions of Medication Adherence and Persistence in Research Employing Electronic Databases,” Medical Care 51, no. S8 (2013): S11–S21, 10.1097/MLR.0b013e31829b1d2a. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Fujioka K., Plodkowski R., O'Neil P. M., Gilder K., Walsh B., and Greenway F. L., “The Relationship Between Early Weight Loss and Weight Loss at 1 Year With Naltrexone ER/Bupropion ER Combination Therapy,” International Journal of Obesity 40, no. 9 (2016): 1369–1375, 10.1038/ijo.2016.67. [DOI] [PubMed] [Google Scholar]
- 18. Gossmann M., Butsch W. S., and Jastreboff A. M., “Treating the Chronic Disease of Obesity,” Medical Clinics of North America 105, no. 6 (2021): 983–1016, 10.1016/j.mcna.2021.06.005. [DOI] [PubMed] [Google Scholar]
- 19. Lee S. and Kuk J. L., “Changes in Fat and Skeletal Muscle With Exercise Training in Obese Adolescents: Comparison of Whole‐Body MRI and Dual Energy X‐Ray Absorptiometry,” Obesity 21, no. 10 (2013): 2063–2071, 10.1002/oby.20448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Suran M., “As Ozempic's Popularity Soars, Here's What to Know About Semaglutide and Weight Loss,” JAMA 329, no. 19 (2023): 1627–1629, 10.1001/jama.2023.2438. [DOI] [PubMed] [Google Scholar]
- 21. Tian Y. and Robinson J. D., “Content Analysis of Health Communication,” in Research Methods in Health Communication: Principles and Application (Routledge, 2014), 190–212, https://www.taylorfrancis.com/chapters/edit/10.4324/9780203115299‐13/content‐analysis‐health‐communication‐yan‐tian‐james‐robinson. [Google Scholar]
- 22. Moreno A. I. and Swales J. M., “Strengthening Move Analysis Methodology Towards Bridging the Function‐Form Gap,” English for Specific Purposes 50 (2018): 40–63, 10.1016/j.esp.2017.11.006. [DOI] [Google Scholar]
- 23. Kind A. J. H. and Buckingham W. R., “Making Neighborhood‐Disadvantage Metrics Accessible—The Neighborhood Atlas,” New England Journal of Medicine 378, no. 26 (2018): 2456–2458, 10.1056/NEJMp1802313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Austin S. R., Wong Y. N., Uzzo R. G., Beck J. R., and Egleston B. L., “Why Summary Comorbidity Measures Such as the Charlson Comorbidity Index and Elixhauser Score Work,” Medical Care 53, no. 9 (2015): e65–e72, 10.1097/MLR.0b013e318297429c. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Du Prel J. B., Röhrig B., Hommel G., and Blettner M., “Choosing Statistical Tests,” Deutsches Ärzteblatt International 107 (2010): 343–348, 10.3238/arztebl.2010.0343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Liu B. Y. and Rome B. N., “State Coverage and Reimbursement of Antiobesity Medications in Medicaid,” JAMA 331, no. 14 (2024): 1230–1232, 10.1001/jama.2024.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Rodriguez P. J., Goodwin Cartwright B. M., Gratzl S., et al., “Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity,” JAMA Internal Medicine 184 (2024): 1056, 10.1001/jamainternmed.2024.2525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Gasoyan H., Pfoh E. R., Schulte R., Sullivan E., Le P., and Rothberg M. B., “Association of Patient Characteristics and Insurance Type With Anti‐Obesity Medications Prescribing and Fills,” Diabetes, Obesity & Metabolism 26 (2024): 1687–1696, 10.1111/dom.15473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Xu Y., Carrero J. J., Chang A. R., et al., “Titration and Discontinuation of Semaglutide for Weight Management in Commercially Insured US Adults,” Obesity 33, no. 7 (2025): 1243–1248, 10.1002/oby.24315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Almohaileb F. I., Le Roux C. W., and Crotty M., “Why do Patients With Obesity Discontinue Glucagon‐Like Peptide 1 Analogues?,” Diabetes, Obesity & Metabolism 27 (2025): 5342–5345, 10.1111/dom.16531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Klein H. E., “Rising Costs Lead Insurers to Drop Weight Loss Drug Coverage, Further Increasing Patient Burden,” American Journal of Managed Care 30, no. Spec. 10 (2024): SP781–SP782, 10.37765/ajmc.2024.89614. [DOI] [Google Scholar]
- 32. Gasoyan H. and Sarwer D. B., “Addressing Insurance‐Related Barriers to Novel Antiobesity Medications: Lessons to Be Learned From Bariatric Surgery,” Obesity 30, no. 12 (2022): 2338–2339, 10.1002/oby.23556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Wright D. R., Guo J., and Hernandez I., “A Prescription for Achieving Equitable Access to Antiobesity Medications,” JAMA Health Forum 4, no. 4 (2023): e230493, 10.1001/jamahealthforum.2023.0493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34. Cologne J., Takahashi I., French B., et al., “Association of Weight Fluctuation With Mortality in Japanese Adults,” JAMA Network Open 2, no. 3 (2019): e190731, 10.1001/jamanetworkopen.2019.0731. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Bangalore S., Fayyad R., Laskey R., DeMicco D. A., Messerli F. H., and Waters D. D., “Body‐Weight Fluctuations and Outcomes in Coronary Disease,” New England Journal of Medicine 376, no. 14 (2017): 1332–1340, 10.1056/NEJMoa1606148. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data S1: oby70058‐sup‐0001‐Supinfo.docx.
Table S1: Examples of how extracted textual data were categorized.
Table S2: Characteristics of patients who did and did not discontinued treatment with semaglutide or tirzepatide for obesity at 1 year, N = 8184.
Table S3: Reasons for obesity pharmacotherapy discontinuation by year of treatment initiation, N = 288.
Table S4: Reasons for obesity pharmacotherapy discontinuation by index medication, N = 288.
Table S5: Results of the sensitivity analysis.
Data Availability Statement
The dataset generated during the current study is not publicly available to preserve patient confidentiality. However, the dataset is available from the corresponding author to academic investigators following receipt of a signed data‐sharing agreement and after reviewing the study protocol (approved by a local institutional review board or research ethics committee), statistical analysis plan, and publication plan. The Cleveland Clinic Institutional Review Board and the Law Department must approve the request before sharing the deidentified data. The corresponding author will respond to these requests within 2 months of receipt.