Titration and discontinuation of semaglutide for weight management in commercially insured US adults.

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Published in final edited form as: Obesity (Silver Spring). 2025 Jun 4;33(7):1243–1248. doi: 10.1002/oby.24315 Titration and discontinuation of semaglutide for weight management in commercially insured US adults Yunwen Xu 1 , Juan J Carrero 2, 3 , Alexander R Chang 4 , Lesley A Inker 5 , Donglan Zhang 6, 7 , Amrita Mukhopadhyay 7, 8, 10 , Saul B Blecker 7, 8, 9 , Leora I Horwitz 7, 8 , Morgan E Grams 1, 7, 8 , Jung-Im Shin 1 Author information Article notes Copyright and License information 1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, US 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden 3 Division of Nephrology, Department of Clinical Sciences, Karolinska Institute, Danderyd Hospital, Stockholm, Sweden 4 Departments of Nephrology and Population Health Sciences, Geisinger, Danville, PA, US 5 Division of Nephrology, Department of Internal Medicine, Tufts Medical Center, Boston, MA, US 6 Center for Population Health and Health Services Research, Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, US 7 Department of Population Health, New York University Grossman School of Medicine, New York, NY, US 8 Department of Medicine, New York University Grossman School of Medicine and Langone Health, New York, NY, US 9 Center for Healthcare Innovation and Delivery Science, New York University Langone Health, New York, New York 10 Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine and Langone Health, New York, New York, USA ✉ Corresponding author: Jung-Im Shin, jshin19@jhmi.edu Issue date 2025 Jul. PMC Copyright notice PMCID: PMC12213178  NIHMSID: NIHMS2079788  PMID: 40464214 The publisher's version of this article is available at Obesity (Silver Spring) Abstract Objective: To examine real-world dose titration patterns of semaglutide for weight management (Wegovy) in US adults and identify characteristics associated with early discontinuation. Methods: We identified 15,811 commercially insured adults who started semaglutide for weight management (administrated through single-dose pre-filled pens) between June 2021 and December 2023. We depicted dose titration patterns over five months and identified factors associated with discontinuation using multivariable Cox regression. Sensitivity analyses examined patterns after supply shortage resolution (post-October 2023). Results: Most semaglutide users deviated from the recommended monthly dose escalation schedule within the first five months. By the fifth month, nearly half (46%) had discontinued the treatment, with similar rates (48%) among those initiating after supply stabilization. Discontinuation was strongly associated with copayment amount, with rates increased from 41% in the lowest quintile ($1-$54 per month) to 51% in the highest quintile ($161-$1,460 per month). Higher discontinuation rates were also associated with lower household income and education level. Conclusions: The deviations from the recommended dose escalation schedule and high discontinuation rate among real-world semaglutide users indicate important challenges in the delivery of evidence-based care. Policy interventions that reduce financial barriers to the persistence of semaglutide are needed. Keywords: semaglutide, weight management, dose titration, discontinuation, health disparities Introduction Once-weekly subcutaneous semaglutide (Wegovy), a glucagon-like peptide-1 receptor agonists (GLP-1RAs), was approved by the United States (US) Food and Drug Administration (FDA) in 2021 for weight management. While landmark clinical trials demonstrated significant weight loss,( 1 – 5 ) real-world effectiveness may be limited by deviations from recommended regimens and treatment discontinuation.( 6 ) Moreover, weight regain after discontinuation is associated with adverse cardiovascular effects.( 7 ) To maximize efficacy and minimize gastrointestinal side effects, the label suggests that adult users start semaglutide at 0.25 mg, escalating monthly to a maintenance dose of 2.4 mg (or 1.7 mg if not tolerated) by the fifth month.( 8 ) However, it remains unclear how this recommended titration regimen is followed in real-world settings, and how often it is discontinued, especially since semaglutide therapy for weight loss is expensive. Given the sparse real-world data, this study aims to characterize dose titration patterns and early treatment discontinuation rates among adult semaglutide users in the US. Methods This study used de-identified administrative claims data from the Optum Labs Data Warehouse on over 200 million enrollees, which represent a mixture of age and geographical regions across the US.( 9 ) In the US, semaglutide for weight management (Wegovy) requires a prescription from a licensed healthcare provider and prior authorization from most insurance plans for coverage. We constructed a cohort of adults who initiated semaglutide for weight management between June 4, 2021 (approval date) and December 31, 2023, with continuous commercial insurance coverage for six months before and after the initial dispensation. Study patients were followed up for six months ( Figure S1 ). This study was approved by the institutional review board of the Johns Hopkins Bloomberg School of Public Health. The use of semaglutide for weight management (administrated through a single-dose pre-filled pen) was ascertained based on National Drug Codes ( Table S1 ) as recorded in the pharmacy claims. We described dose titration patterns for all individuals at 1, 2, 3, 4, and 5 months after the first dispensation using a Sankey diagram, based on dates of dispensation, dosage, and days’ supply extracted from pharmacy claims. If an individual filled multiple semaglutide prescriptions at a time, we assumed the person used the lower dosage first and then the higher dosage after the exhaustion of the lower dosage with no gaps. We calculated the proportion of individuals reaching the maintenance dosage of 2.4 mg or 1.7 mg over the follow-up. Discontinuation was defined as a gap of more than 30 days between the exhaustion of last dispensation and the new dispensation.( 10 ) Multivariable Cox proportional hazard regression was used to examine associations between individual characteristics and time-to-discontinuation. We obtained age, sex, education level, and household income from the member files and copay data from pharmacy claims. Diabetes and cardiovascular disease (i.e., myocardial infarction, stroke, peripheral arterial disease) were ascertained based on the presence of International Classification of Diseases 9th and 10th revisions codes ( Table S2 ) in one inpatient or two outpatient medical claims within 2 years preceding the initiation. We conducted multiple sensitivity analyses to assess the robustness of our findings. First, we examined patterns using a gap of more than 15 days for discontinuation definition, as the FDA-approved product labeling advises that missing therapy for two weeks may necessitate a reinitiation of treatment.( 8 ) Second, given that individuals might have prior exposure to other semaglutide products at lower doses (Ozempic approved for type 2 diabetes treatment in 2017 and cardiovascular risk reduction in 2020), we conducted an analysis restricted to individuals initiating at the recommended starting dosage of 0.25 mg per week. Lastly, we examined discontinuation among patients initiating semaglutide for weight management after October 11, 2023, when the FDA announced full restoration of supply.( 11 ) Statistical significance was defined as with a two-sided P <0.05. All analyses were conducted using Stata (version 16.1; StataCorp LLC, College Station, TX, USA). Results Among 15,811 adult semaglutide users ( Table 1 ), 69% started at the recommended 0.25 mg dose ( Figure 1A ), and 57% had ever reached the maintenance doses (22% for 1.7 mg and 34% for 2.4 mg) over the follow-up. By the fifth month, the cumulative discontinuation rate was 46% ( Figure 1B ). Table 1. Characteristics of the study population at the initial dispensation of semaglutide for weight management Characteristics Cohort N=15,811 Age, years, mean (SD) 46 (11) 18-29 1,131 (7%) 30-44 5,993 (38%) 45-64 8,291 (52%) ≥65 396 (3%) Female 12,113 (77%) Diabetes 1,008 (6%) Cardiovascular diseases 550 (3%) Education ≤High school 2,380 (15%) >High school to <College 8,323 (53%) ≥College 3,858 (24%) Unknown 1,250 (8%) Household income category, USD/year <40K 2,607 (16%) 40 to <75K 2,838 (18%) 75 to <125K 3,927 (25%) 125 to <200K 2,533 (16%) ≥200K 2,432 (15%) Unknown 1,474 (9%) Copay per month, USD 1 st quintile: 1-54 5,244 (33%) 2 nd quintile: 55-64 1,842 (12%) 3 rd quintile: 65-80 2,599 (16%) 4 th quintile: 81-160 3,499 (22%) 5 th quintile: 161-1460 2,627 (17%) Open in a new tab Education and annual household income were imputed using data from both public and private consumer information. Unequal quintile size is due to ties of the copay. Abbreviations: SD, standard deviation; USD, U.S. dollar. Figure 1. Dose titration patterns (A) and discontinuation (B) of semaglutide for weight management within the first five months of treatment. Open in a new tab *Discontinuation at each month is calculated as the percentage of individuals who discontinued, using the number of individuals who continued in the prior month as the denominator. Discontinuation of semaglutide for weight management varied across socioeconomic subgroups, ranging from 41% to 51%. A high 30-day copay was associated with discontinuation in a dose-dependent manner ( Figure 2 ). Individuals with the highest copay bracket (5 th quintile: $161-$1,460) were 33% more likely to discontinue treatment than those with the lowest copay (1 st quintile: $1-$54). Other factors associated with a higher likelihood of discontinuation included being aged 18-29 or ≥65 years, having a high school education or less, and having an annual household income of $75K or less. Figure 2. Baseline characteristics associated with semaglutide discontinuation within the first five months of treatment. Open in a new tab Abbreviation: CI, confidence interval; USD, U.S. dollar. Using a more stringent 15-day gap definition, overall dose titration patterns were similar, and the cumulative discontinuation rate was 56% ( Figure S2 ). Among adults initiating semaglutide for weight management at 0.25 mg weekly, similar dose titration patterns were observed, with 50% having discontinued during the five-month follow-up ( Figure S3 ). In the cohort of 1,128 adults initiating after supply restoration, the cumulative discontinuation rate remained consistent at 48%. Discussion Our study showed that few users of semaglutide for weight management followed the recommended dose escalation schedule to achieve the maintenance dosage within the first five months, and nearly half of semaglutide treatment discontinued during this period. These patterns persisted even after supply stabilization, suggesting factors beyond supply availability influence treatment continuation. The discontinuation rate was higher among individuals with higher copay amounts and those with lower socioeconomic status, suggesting structural barriers to accessing and affording this effective treatment. Real-world dose escalation and continuation of semaglutide lagged behind that observed in clinical trials, where 83%-94% of participants followed the up-titration schedule and maintained the target dosage up to 68 weeks.( 1 – 4 ) Our findings align with previous studies showing consistently low adherence and high discontinuation rates of GLP-1RAs within one year among patients with type 2 diabetes or obesity.( 12 – 14 ) The substantial early discontinuation observed across all sociodemographic subgroups suggests that factors beyond measured characteristics influence treatment persistence. This gap between trial and real-world implementation has important clinical implications, as weight regain from treatment discontinuation may increase the risk of adverse cardiovascular outcomes.( 6 , 7 ) These findings underscore the need for strategies to support long-term treatment adherence in routine clinical practice. The deviation from the recommended schedule in our study likely reflects multifaceted factors. Clinically, side effects such as gastrointestinal adverse events were the most common reason for treatment cessation during clinical trial’s run-in period (5.3%),( 4 ) and in real-world users as well.( 15 ) Perceived non-efficacy (i.e., not reaching the expected body weight targets) may also explain early discontinuation. However, the strong linear association between copay amount and discontinuation observed in our study, as well as in others,( 16 , 17 ) suggests that high out-of-pocket costs and limited insurance coverage are significant barriers to treatment adherence. Other real-world challenges such as varying prior authorization requirements can also hinder adherence.( 18 ) Significant socioeconomic disparities in the discontinuation of semaglutide for weight management mirror patterns previously reported in GLP-1RA use among persons with type 2 diabetes.( 19 ) These findings echo concerns that cost-related treatment discontinuation occur more frequently among economically disadvantaged groups.( 18 ) This is particularly concerning given that obesity and related comorbidities disproportionately affect those with lower socioeconomic status,( 20 ) creating a cycle where those most in need of treatment face the greatest barriers to maintaining it. Efforts to ensure access to initiation and persistence of obesity treatment is essential to prevent worsening health disparities. Our study has several strengths. Our study is one of the first to comprehensively assess real-world titration patterns of semaglutide for weight management in US clinical practice, compared directly to trial-based protocols. The large, nationwide claims database enabled robust analyses of treatment patterns across pre- and post-supply shortage periods. Several limitations warrant consideration. First, our analysis focused exclusively on prescriptions under the brand name Wegovy, without accounting for transitions to alternative GLP-1 RA formulations. Second, we didn’t have BMI data, and were unable to determine reasons for discontinuation or assess the clinical appropriateness of observed patterns. Third, due to the absence of data on manufacturer-sponsored drug coupon usage in the Optum database, we were unable to include this factor in the analysis, which may have affected copay amounts and discontinuation rates for some individuals. Regardless, we observed higher discontinuation rates with the higher copay amounts ultimately paid by patients. In addition, our analysis cannot capture prescriptions paid entirely out-of-pocket, which may lead to an overestimation of discontinuation rates. Lastly, while our 6-month follow-up period specifically examined adherence to recommended initial titration protocols, future studies should explore longer-term persistence patterns, as well as the clinical outcomes associated with different titration approaches and with discontinuation. Conclusions This real-world analysis of semaglutide for weight management revealed significant deviations from recommended dose escalation schedules, with nearly half of patients discontinuing within five months. These patterns persisted after supply stabilization and were strongly associated with copayment amounts and socioeconomic status, highlighting structural barriers to maintaining this highly effective obesity treatment. Supplementary Material Supinfo Table S1. National Drug Codes of semaglutide for weight management Table S2. International Classification of Diseases (ICD) codes of comorbidities Figure S1. Dose escalation schedule and study design Figure S2. Sensitivity analysis of dose titrations (A) and discontinuation (B) of semaglutide for weight management using a 15-day gap definition during five months after the first dispensation Figure S3. Sensitivity analysis of dose titrations (A) and discontinuation (B) of semaglutide for weight management during five months after the first dispensation among adults initiating at 0.25 mg weekly NIHMS2079788-supplement-Supinfo.docx (1.4MB, docx) Study Importance. What is already known about this subject? Clinical trials demonstrated efficacy of semaglutide for weight management using a standardized monthly dose escalation protocol. What are the new findings in your manuscript? Real-world titration patterns were more variable than the suggested titration pattern, and nearly half of new users discontinued treatment within five months, with these patterns persisting after supply stabilization. There was a strong dose-response relationship between copayment amount and discontinuation, with higher rates among socioeconomically disadvantaged groups. How might your results change the direction of research or the focus of clinical practice? Future research is needed to assess long-term treatment patterns of semaglutide, as well as the clinical outcomes associated with different titration patterns and with discontinuation. Our findings may stimulate policy changes that promote equitable access to initiate and continue effective pharmacotherapy for obesity. Funding: This research is supported by R01 DK115534 and R01 DK139324 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The funding sources had no role in the design and conduct of the study, analyses or interpretation of the data, and preparation or final approval of the manuscript. Disclosure: All authors do not have conflicts of interest relevant to this article. References: 1. Wilding JPH, Batterham RL, Calanna S, Davies M, Gaal LFV, Lingvay I, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021. Mar 17;384(11):989–1002. [ DOI ] [ PubMed ] [ Google Scholar ] 2. Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. The Lancet. 2021. Mar 13;397(10278):971–84. [ DOI ] [ PubMed ] [ Google Scholar ] 3. Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, et al. 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Socioeconomic status and use of obesogenic and anti-obesity medications in the United States: A population-based study. The Lancet Regional Health – Americas [Internet]. 2022. Jul 1 [cited 2024 Oct 23];11. Available from: https://www.thelancet.com/journals/lanam/article/PIIS2667-193X(22)00066-7/fulltext [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. Supplementary Materials Supinfo Table S1. National Drug Codes of semaglutide for weight management Table S2. International Classification of Diseases (ICD) codes of comorbidities Figure S1. Dose escalation schedule and study design Figure S2. Sensitivity analysis of dose titrations (A) and discontinuation (B) of semaglutide for weight management using a 15-day gap definition during five months after the first dispensation Figure S3. Sensitivity analysis of dose titrations (A) and discontinuation (B) of semaglutide for weight management during five months after the first dispensation among adults initiating at 0.25 mg weekly NIHMS2079788-supplement-Supinfo.docx (1.4MB, docx) ACTIONS View on publisher site PDF (722.6 KB) Cite Collections Permalink RESOURCES Similar articles Cited by other articles Links to NCBI Databases Follow NCBI NCBI on X (formerly known as Twitter) NCBI on Facebook NCBI on LinkedIn NCBI on GitHub NCBI RSS feed Connect with NLM NLM on X (formerly known as Twitter) NLM on Facebook NLM on YouTube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov Back to Top

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