Abstract
Introduction
Semaglutide 2.4 mg injection (Wegovy®), a glucagon-like peptide-1 (GLP-1) receptor agonist, was approved by the US Food and Drug Administration for weight management in June 2021. Tirzepatide, a glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, was approved for type 2 diabetes mellitus (T2DM; Mounjaro®) in May 2022 and weight management (Zepbound®) in November 2023. Due to limited data on the long-term effectiveness of these medications, this study assessed real-world weight loss with semaglutide 2.4 mg or tirzepatide after 1 year in patients with overweight or obesity and without T2DM.
Methods
This retrospective cohort study included adults with overweight or obesity and ≥ 1 pharmacy claim for semaglutide 2.4 mg or tirzepatide in the US Komodo Health database between June 4, 2021, and December 15, 2023. Patients had continuous enrollment for 1 year before (baseline period) and 1 year after (follow-up period) the index date (date of treatment initiation) and persistence on therapy (no gap of > 30 days’ supply) during follow-up. Patients with T2DM at baseline were excluded. Weight change from index to 1 year was descriptively assessed.
Results
Overall, 9916 patients were included (semaglutide 2.4 mg, n = 6794; tirzepatide, n = 3122). Baseline characteristics were descriptively similar for semaglutide 2.4 mg and tirzepatide: mean age was 47.8 and 49.5 years, 79.8% and 77.9% were female, and mean index weight was 104.5 and 104.9 kg, respectively. After 1 year of follow-up, the mean weight loss from baseline with semaglutide 2.4 mg and tirzepatide was − 14.6 and − 17.2 kg, respectively, with percent weight loss of − 14.1% and − 16.5%. Most (83.5%) patients treated with semaglutide 2.4 mg reached the maximum dose (2.4 mg), while 25.9% of patients treated with tirzepatide reached the maximum dose (15 mg).
Conclusion
Findings suggest semaglutide 2.4 mg and tirzepatide are used in descriptively similar populations and both resulted in clinically meaningful weight loss after 1 year of treatment.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12325-025-03340-2.
Keywords: Clinical practice, Obesity, Overweight, Real-world evidence, Semaglutide, Tirzepatide, Weight loss, Weight management
Plain Language Summary
Obesity, a condition of higher than normal body fat, is common among adults. Obesity contributes to many health problems and higher medical costs compared with adults with normal weight. This study examined the weight loss of patients treated with two drugs recently approved by the US Food and Drug Administration for weight management: semaglutide and tirzepatide. Both drugs affect weight by impacting the glucagon-like peptide-1 system. The US Komodo Health database, which provides patient medical history for over 140 million US patients, including medical and pharmacy claims, clinical observations, and laboratory results, was used to examine data for adults with overweight or obesity who had at least one pharmacy claim for semaglutide or tirzepatide. Weight change 1 year after the start of treatment was measured. This study found that patients treated with semaglutide and tirzepatide had generally similar characteristics, such as age, gender, and starting weight before treatment. After 1 year of treatment, the average weight loss with semaglutide was –14.6 kg, or 14.1% of body weight; the average weight loss with tirzepatide was –17.2 kg, or 16.5% of body weight. Findings from this study suggest that semaglutide and tirzepatide are used for patients with similar characteristics and both led to meaningful weight loss after 1 year of treatment. Given the study size and patient information from the database, the results likely reflect outcomes for real-world patients taking semaglutide or tirzepatide for obesity management.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12325-025-03340-2.
Key Summary Points
| Why carry out this study? | |
| Due to the relatively recent approval of tirzepatide, few studies have evaluated long-term real-world weight loss with both semaglutide 2.4 mg and tirzepatide among patients with overweight or obesity and without type 2 diabetes mellitus (T2DM) | |
| This retrospective study examined real-world weight loss outcomes over 1 year of follow-up in patients with overweight or obesity and without T2DM who were treated with semaglutide 2.4 mg or tirzepatide | |
| What was learned from the study? | |
| Among patients with overweight or obesity and without T2DM, semaglutide 2.4 mg and tirzepatide appeared to be used in descriptively similar populations | |
| After 1 year of treatment, patients who received semaglutide 2.4 mg or tirzepatide achieved clinically meaningful weight loss | |
| These real-world findings support the effectiveness of both semaglutide 2.4 mg and tirzepatide in managing weight in patients with overweight or obesity and offer valuable insights for routine clinical practice |
Introduction
Obesity is a prevalent, chronic condition characterized by abnormal or excessive fat accumulation; individuals who have a body mass index (BMI) of ≥ 30 kg/m2 are classified as having obesity [1]. This condition is a significant global public health issue, with an estimated prevalence that rose to 41.9% among adults in the US between 2017 and 2020 [2]. Obesity contributes to various medical conditions, such as type 2 diabetes mellitus (T2DM), hypertension, lipid disorders, cardiovascular disease, metabolic dysfunction–associated steatohepatitis, gallbladder disease, osteoarthritis, and certain cancers [3–5]. Obesity-related comorbidities also lead to a substantial increase in US medical costs, with annual costs being $2505 higher among adults with obesity compared with those with normal weight, which totals to an estimated $260.6 billion in aggregated costs [3]. Obesity also confers a substantial mortality risk and contributed to > 10,200 deaths in the US in 2020 [6].
Management options for obesity include caloric restriction, behavioral modification, bariatric surgery, and medication [7]. The US Food and Drug Administration has approved several medications for obesity management, with clinical guidelines recommending pharmacologic treatment as a part of a comprehensive strategy for disease management among individuals with a BMI of 27–29.9 kg/m2 and ≥ 1 obesity-related complication or with a BMI ≥ 30 kg/m2 [8, 9]. Semaglutide 2.4 mg injection (Wegovy®, Novo Nordisk®), a glucagon-like peptide-1 (GLP-1) receptor agonist, was approved in June 2021 for chronic weight management in adults with overweight and ≥ 1 weight-related condition or obesity based on demonstrated weight reduction in clinical trials [10]. Additionally, tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, was approved in May 2022 for adults with T2DM (Mounjaro®, Eli Lilly and Company) and in November 2023 for chronic weight management (Zepbound®, Eli Lilly and Company) [11, 12].
Given the relatively recent approval of semaglutide 2.4 mg and tirzepatide, real-world evidence on the effectiveness of these therapies for chronic weight management is limited. Therefore, the SHAPE study (Real-World Weight Loss Observed With Semaglutide and Tirzepatide in Patients with OverweigHt or Obesity And Without TyPE 2 Diabetes) aimed to evaluate the effectiveness of semaglutide 2.4 mg and tirzepatide in patients with overweight or obesity and without T2DM in routine clinical practice over a 1-year follow-up period.
Methods
Study Design and Patient Population
This retrospective, noninterventional cohort study included adult patients with overweight or obesity and without T2DM who were identified from the US Komodo Health database (Supplementary Fig. S1). The US Komodo Health database is a comprehensive database that contains > 65 billion records from 2012 to 2025. The database provides longitudinal patient history across the continuum of care during patient enrollment, including medical and pharmacy claims, clinical observations, and laboratory results. These data sources include links with electronic medical records and closed claims capture for > 140 million US patients.
The study period extended from June 4, 2020, through February 15, 2025. Eligible patients had initiated treatment and had ≥ 1 pharmacy claim of any dose strength of semaglutide 2.4 mg or tirzepatide in the US Komodo Health database between June 4, 2021 (approval date of semaglutide 2.4 mg), and December 15, 2023. The index date was defined as the date of the first observed pharmacy claim for semaglutide 2.4 mg or tirzepatide, and the index therapy was defined as the first observed therapy. Patients were required to be persistent on the index therapy (having no gap in therapy of > 30 days’ supply of medication, allowing for stockpiling) over the 1-year follow-up period. Tirzepatide was evaluated at the molecule level to maximize sample size; any use of Mounjaro among patients without T2DM was assumed to be off-label for weight management [13, 14]. Semaglutide injection indicated for T2DM (Ozempic®) was excluded because of different dose strengths for maintenance treatment (Ozempic®, 1.0 mg and 2.0 mg [15]; Wegovy, 1.7 mg and 2.4 mg [16]), whereas available dose strengths are consistent for Mounjaro [17] and Zepbound [18]. There were no requirements regarding dosing (e.g., starting on the lowest dose and titrating on a specific schedule, maximum dose achieved) over the 1-year follow-up period; patients were only required to remain persistent on treatment.
Full study eligibility criteria are described in Fig. 1. In summary, patients were required to have ≥ 1 weight measurement on the index date (within 90 days before or 14 days after) as well as ≥ 1 weight measurement at 1 year after the index date (within 30 days before or 60 days after) for assessment of changes in weight. Furthermore, patients were required to have continuous enrollment in medical and pharmacy insurance for 1 year before (baseline period) and 1 year after (follow-up period) the index date. Patients were additionally required to have ≥ 1 of the following based on data from the 1-year baseline period or the index date: ≥ 1 International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code or electronic medical record indicating overweight (BMI of 25–29.9 kg/m²) with ≥ 1 obesity-related complication (identified through ICD-10 diagnosis codes) or ≥ 1 ICD-10 diagnosis code or electronic medical record indicating obesity (BMI ≥ 30 kg/m2; Supplementary Tables S1, S2). Patients were excluded if they had evidence of T2DM, which was defined as having ≥ 1 ICD-10 Clinical Modification diagnosis code for T2DM (Supplementary Table S3), during the baseline period or on the index date; patients with other forms of diabetes not associated with these ICD-10 diagnosis codes were included in the study. Recent real-world studies evaluating weight loss with tirzepatide in patients with obesity have similarly excluded individuals with T2DM [13, 14, 19].
Fig. 1.
Cohort attrition. BMI, body mass index; T2DM, type 2 diabetes mellitus. aMust be a paid claim with a positive “days of supply” field. bThe index date was the date of the first observed claim (semaglutide or tirzepatide), and the first observed claim defined the index cohort. cExcluded patients with both medications on the index date. dIf multiple weights were reported within the time frame, the average was taken. ePersistence was defined as having no gap in therapy > 30 days and allowed for stockpiling
Study Assessments and Endpoints
Demographic characteristics (e.g., age, sex) were assessed on the index date, and clinical characteristics (e.g., obesity-related comorbidities) were assessed over the baseline period. Weight outcomes included the absolute and percent changes in weight from the index date to 1 year of post-index follow-up (index date + 365 days). If multiple weights were available for a patient within the time frame, the average of the available weights was used. The proportion of patients in each treatment cohort who achieved clinically relevant weight loss (i.e., ≥ 5% [9]) was then evaluated. The maximum dose reached over the course of the year was also assessed for both cohorts.
Statistical Analysis
Descriptive statistics were used to characterize each treatment cohort and to summarize weight change over the 1-year follow-up period and the maximum dose reached for the two treatment cohorts. No formal statistical comparisons were made within or between treatment cohorts.
Ethics Compliance
This study was conducted in accordance with relevant guidelines and regulations, including the principals of the Declaration of Helsinki of 1964 and its later amendments. This study used only de-identified patient records and did not involve the collection, use, or transmittal of individually identifiable data. The Department of Health and Human Services does not consider analysis of de-identified secondary data to meet the definition for human subject research. Therefore, this study was exempt from federal regulations covering human subject research and did not require institutional review board review. This is as per exemption (d)4 from 45 CFR 46.104. Novo Nordisk Inc. has a data access license to the Komodo Health database.
Results
Patient Baseline Characteristics
Overall, a total of 9916 patients met the eligibility criteria and were included in the study; of these, 6794 (68.5%) patients received continuous treatment with semaglutide 2.4 mg and 3122 (31.5%) received continuous treatment with tirzepatide over the 1-year follow-up period (Fig. 1). Demographic and clinical characteristics were generally descriptively similar between the cohorts (Tables 1, 2). Briefly, the mean (standard deviation [SD]) age was similar between the two cohorts at 47.8 (10.3) years of age in the semaglutide 2.4 mg cohort and 49.5 (10.9) years of age in the tirzepatide cohort. Notably, more than one-third (35–38%) of the patients in both cohorts were 45 to 54 years of age, with few (3.4–8.6%) ≥ 65 years of age. Patients in both cohorts were predominantly female and accounted for 79.8% and 77.9% of those treated with semaglutide 2.4 mg and tirzepatide, respectively. The most common quarter (Q)-year at initiation was Q1-2023 for patients who were treated with semaglutide 2.4 mg (37.0%) and Q4-2022 for patients who were treated with tirzepatide (28.9%).
Table 1.
Baseline demographic characteristics
| Characteristic | Semaglutide 2.4 mg (n = 6794) |
Tirzepatide (n = 3122) |
|---|---|---|
| Age, years | ||
| Mean (SD) | 47.8 (10.3) | 49.5 (10.9) |
| Median (IQR) | 48 (41–55) | 50 (42–57) |
| Age group, n (%) | ||
| 18–34 years | 725 (10.7) | 269 (8.6) |
| 35–44 years | 1817 (26.7) | 727 (23.3) |
| 45–54 years | 2406 (35.4) | 1174 (37.6) |
| 55–64 years | 1614 (23.8) | 684 (21.9) |
| ≥ 65 years | 232 (3.4) | 268 (8.6) |
| Sex, n (%) | ||
| Female | 5422 (79.8) | 2431 (77.9) |
| Male | 1314 (19.3) | 651 (20.9) |
| Unknown | 58 (0.9) | 40 (1.3) |
| Race/ethnicity, n (%) | ||
| Asian or Pacific Islander | 146 (2.1) | 58 (1.9) |
| Black or African American | 772 (11.4) | 302 (9.7) |
| Hispanic or Latino | 663 (9.8) | 297 (9.5) |
| White | 4664 (68.6) | 2074 (66.4) |
| Other | 160 (2.4) | 115 (3.7) |
| Unknown | 389 (5.7) | 276 (8.8) |
| Region, n (%) | ||
| West | 490 (7.2) | 284 (9.1) |
| Midwest | 1110 (16.3) | 427 (13.7) |
| Northeast | 3005 (44.2) | 890 (28.5) |
| South | 2185 (32.2) | 1520 (48.7) |
| Unknown | 4 (0.1) | 1 (< 0.1) |
| Index quarter-year, n (%) | ||
| Q2-2021 | 15 (0.2) | 0 |
| Q3-2021 | 324 (4.8) | 0 |
| Q4-2021 | 452 (6.7) | 0 |
| Q1-2022 | 511 (7.5) | 0 |
| Q2-2022 | 180 (2.6) | 32 (1.0) |
| Q3-2022 | 118 (1.7) | 730 (23.4) |
| Q4-2022 | 246 (3.6) | 903 (28.9) |
| Q1-2023 | 2517 (37.0) | 459 (14.7) |
| Q2-2023 | 1433 (21.1) | 348 (11.1) |
| Q3-2023 | 661 (9.7) | 276 (8.8) |
| Q4-2023 | 337 (5.0) | 374 (12.0) |
| Medical insurance, n (%) | ||
| Commercial | 6010 (88.5) | 2603 (83.4) |
| Medicare | 274 (4.0) | 315 (10.1) |
| Medicaid | 455 (6.7) | 169 (5.4) |
| Dual (Medicare and Medicaid) | 23 (0.3) | 31 (1.0) |
| Unknown | 32 (0.5) | 4 (0.1) |
| Prescription insurance, n (%) | ||
| Commercial | 6095 (89.7) | 2637 (84.5) |
| Medicare | 144 (2.1) | 259 (8.3) |
| Medicaid | 412 (6.1) | 145 (4.6) |
| Dual (Medicare and Medicaid) | 18 (0.3) | 28 (0.9) |
| Unknown | 125 (1.8) | 53 (1.7) |
IQR, interquartile range; Q, quarter; SD, standard deviation
Table 2.
Baseline clinical characteristics
| Characteristic | Semaglutide 2.4 mg (n = 6794) |
Tirzepatide (n = 3122) |
|---|---|---|
| Weight cohort, n (%) | ||
| Obesity | 6599 (97.1) | 2927 (93.8) |
| Overweight + ≥ 1 obesity-related complication | 195 (2.9) | 195 (6.2) |
| Prevalence of obesity-related complications, n (%) | ||
| ≥ 1 of the below obesity-related complications | 6073 (89.4) | 2825 (90.5) |
| Asthma | 977 (14.4) | 412 (13.2) |
| Dyslipidemia | 3090 (45.5) | 1471 (47.1) |
| Gastroesophageal reflux disease | 1725 (25.4) | 755 (24.2) |
| Heart failure with preserved ejection fraction | 31 (0.5) | 33 (1.1) |
| Hypertension | 2823 (41.6) | 1432 (45.9) |
| Knee osteoarthritis | 612 (9.0) | 303 (9.7) |
| Musculoskeletal pain | 3324 (48.9) | 1574 (50.4) |
| Obstructive sleep apnea | 1551 (22.8) | 738 (23.6) |
| Polycystic ovary syndrome | 436 (6.4) | 236 (7.6) |
| Pre-diabetes | 1983 (29.2) | 1261 (40.4) |
| Psoriasis | 168 (2.5) | 63 (2.0) |
| Urinary incontinence | 238 (3.5) | 125 (4.0) |
| Index weight, kg | ||
| Mean (SD) | 104.5 (22.0) | 104.9 (22.7) |
| Median (IQR) | 101.5 (88–118) | 101.8 (88–119) |
IQR, interquartile range; SD, standard deviation
Most patients (97.1% in the semaglutide 2.4 mg cohort and 93.8% in the tirzepatide cohort) were classified as having obesity. The remaining patients were classified as overweight with obesity-related complications. The prevalence of ≥ 1 obesity-related complication at baseline and on the index date was high (89.4% in the semaglutide 2.4 mg cohort and 90.5% in the tirzepatide cohort); the most common obesity-related complications included musculoskeletal pain (48.9% vs 50.4%, respectively), dyslipidemia (45.5% vs 47.1%), and hypertension (41.6% vs 45.9%). The mean index weight was similar between the two cohorts, with patients who were treated with semaglutide 2.4 mg averaging 104.5 kg and those who were treated with tirzepatide averaging 104.9 kg.
Weight Outcomes
After 1 year of follow-up with continuous treatment, the mean (SD) weight was 89.9 (22.4) kg in the semaglutide 2.4 mg cohort and 87.6 (22.6) kg in the tirzepatide cohort (Table 3). The mean (SD) absolute weight loss from the index date to the end of follow-up was − 14.6 (9.9) kg in the semaglutide 2.4 mg cohort and − 17.2 (11.7) kg in the tirzepatide cohort, which represented a mean (SD) percent weight loss of − 14.1% (9.6) and − 16.5% (10.8), respectively. Most patients in both cohorts achieved clinically meaningful [9] weight loss over 1 year, with 84.1% in the semaglutide 2.4 mg cohort and 86.2% in the tirzepatide cohort achieving weight loss of ≥ 5% (Table 3).
Table 3.
Weight outcomes
| Semaglutide 2.4 mg (n = 6794) |
Tirzepatide (n = 3122) |
|
|---|---|---|
| Follow-up weight, kg | ||
| Mean (SD) | 89.9 (22.4) | 87.6 (22.6) |
| Median (IQR) | 86.2 (73.2–102.7) | 83.5 (70.3–100.2) |
| Absolute weight change between index and follow-up, kg | ||
| Mean (SD) | − 14.6 (9.9) | − 17.2 (11.7) |
| Median (IQR) | − 13.9 (− 20.5 to − 8.2) | − 16.5 (− 24.5 to − 9.4) |
| Percent weight change between index and follow-up | ||
| Mean (SD) | − 14.1 (9.6) | − 16.5 (10.8) |
| Median (IQR) | − 13.8 (− 20.1 to − 8.0) | − 16.5 (− 23.7 to − 9.5) |
| Weight loss from index to follow-up, n (%) | ||
| ≥ 5% | 5714 (84.1) | 2691 (86.2) |
| ≥ 10% | 4536 (66.8) | 2304 (73.8) |
| ≥ 15% | 3045 (44.8) | 1749 (56.0) |
| ≥ 20% | 1721 (25.3) | 1169 (37.4) |
IQR, interquartile range; SD, standard deviation
Maximum Dose Reached
Over 1 year of follow-up, most patients in the semaglutide 2.4 mg cohort (83.5%) reached the maximum dose of 2.4 mg, with an additional 11.2% of patients reaching a dose of 1.7 mg (Table 4). For the tirzepatide cohort, the maximum dose achieved varied, with one-quarter (25.9%) of the patients reaching the maximum dose of 15 mg and one-fifth of patients reaching maximum doses of 7.5 mg (19.6%), 10 mg (20.8%), and 12.5 mg (19.1%) each.
Table 4.
Maximum dose reached over the 1-year follow-up period
| Semaglutide 2.4 mg (n = 6794) |
Tirzepatide (n = 3122) |
|
|---|---|---|
| Maximum dose reached, n (%) | ||
| 0.25 mg | 163 (2.4) | – |
| 0.5 mg | 64 (0.9) | – |
| 1.0 mg | 133 (2.0) | – |
| 1.7 mg | 763 (11.2) | – |
| 2.4 mg | 5671 (83.5) | – |
| 2.5 mg | – | 65 (2.1) |
| 5.0 mg | – | 390 (12.5) |
| 7.5 mg | – | 611 (19.6) |
| 10.0 mg | – | 650 (20.8) |
| 12.5 mg | – | 597 (19.1) |
| 15.0 mg | – | 809 (25.9) |
Discussion
This study demonstrated the real-world effectiveness of semaglutide 2.4 mg and tirzepatide treatment in patients with overweight or obesity and without T2DM over a 1-year follow-up period. Baseline demographic and clinical characteristics were generally descriptively similar for patients who initiated semaglutide and tirzepatide, suggesting that these treatments are used in similar patient populations in clinical practice. For instance, the mean age and the proportion of female patients were similar between the two cohorts. Additionally, the high prevalence and generally similar obesity-related complications in both cohorts suggest consistent clinical profiles of the patients who received these treatments.
In this real-world setting, patients who were treated with semaglutide 2.4 mg and tirzepatide had a mean weight loss of − 14.1% and − 16.5% at 1 year, respectively, which represents a clinically meaningful weight loss with both therapies when used in patients with overweight or obesity and without T2DM [20]. Furthermore, real-world data on weight loss from this study are generally consistent with findings at around 1 year from key clinical trials and prior real-world studies of patients with overweight or obesity. In the phase 3, randomized, placebo-controlled STEP-1 trial, patients without T2DM who were treated with semaglutide 2.4 mg achieved a mean weight loss of − 14.9% at 68 weeks (P < 0.001 vs placebo) [21]. Additionally, in a retrospective database study of semaglutide 2.4 mg that included patients with T2DM (5.8%), the mean weight loss was − 14.5% at 1 year (P < 0.001) [22]. Similarly, in the phase 3, randomized, placebo-controlled SURMOUNT-1 trial, patients without T2DM who were treated with tirzepatide 5 mg, 10 mg, and 15 mg achieved a mean weight loss of − 15.0%, − 19.5%, and − 20.9%, respectively, at 72 weeks (all P < 0.001 vs placebo) [23]. Notably, only two-thirds of tirzepatide patients reached doses of 10 mg, 12.5 mg, or 15 mg in the current real-world study. Two retrospective database studies have also evaluated weight outcomes with tirzepatide in patients without T2DM, with reported weight loss of − 11.9% and − 12.9% after 6 months of follow-up [13, 14]; however, no real-world studies have previously evaluated longer-term weight loss with tirzepatide in this patient population.
Only three identified real-world studies have evaluated weight loss among patients with overweight or obesity who were treated with both semaglutide and tirzepatide, but differences in populations, follow-up time, and study design limit comparisons. A prior single-center, retrospective study of patients with overweight or obesity found mean weight loss of − 3.4% and − 7.0% among semaglutide and tirzepatide patients, respectively, without diabetes after 6 months of follow-up; however, the follow-up time was relatively short, there were no requirements for persistence, and small sample sizes (semaglutide, n = 356; tirzepatide, n = 60) limit interpretation [24]. An additional study compared weight loss outcomes for semaglutide and tirzepatide but used data specifically for these medications labeled for T2DM and thus included a large (52%) proportion of patients with T2DM. Results are presented visually by treatment cohort and T2DM status at 12 months in this study, but data points and sample sizes are not stated, preventing interpretation and comparison of outcomes with those from the current study [25]. Lastly, a retrospective cohort study compared post-treatment outcomes for semaglutide and tirzepatide in a population of patients without T2DM. However, this study specifically evaluated outcomes during the 1-year follow-up period after completion of a discreet 6-month treatment period [26]. Given the differences in follow-up times, the concordance in weight loss outcomes between many of these prior studies and the current real-world study reinforces the potential of semaglutide 2.4 mg and tirzepatide as effective treatments for obesity.
Several factors may explain the differences observed between real-world and clinical trial weight loss outcomes. In randomized clinical trials, there is a greater emphasis on achieving the protocol-required maintenance dose, which might not always be the case in real-world clinical practice [21, 23, 25]. Importantly, clinical trials investigating weight loss typically involve more intensive follow-up and support for patients, which may enhance adherence and outcomes compared with routine clinical practice [27]. For example, in both the STEP-1 and SURMOUNT-1 trials, patients attended regular counseling sessions to help with adherence to a reduced-calorie diet (500 cal/day deficit) and increased physical activity regimen (≥ 150 min/week) [21, 23]. Real-world patients may also have a broader range of comorbidities and varying levels of health care access [28]. These factors underscore the importance of considering both clinical trial data and real-world evidence when evaluating the effectiveness of weight management therapies.
The strengths of this study include its large sample size of 9916 patients, which increases the generalizability of the observed weight loss results to the broader US population compared with the smaller patient populations enrolled in randomized clinical trials. Additionally, this study provided information on patient demographic and baseline clinical data, dosing, and weight outcomes and offered a comprehensive view of the real-world effectiveness of semaglutide 2.4 mg and tirzepatide. Long-term effectiveness data over a 1-year follow-up period are a key strength of the study, given the relatively recent approval of tirzepatide.
Limitations of this study include its descriptive, observational design, with no statistical comparisons of outcomes within or between treatment cohorts. This study was intended to provide descriptive insights into the real-world use, weight outcomes, and dosing among patients treated with semaglutide 2.4 mg and tirzepatide. Claims data reflect routine clinical practice rather than mandatory assessments at prespecified time points, which may have impacted the amount of data available for observation. Furthermore, the requirement for patients to have an available weight measurement on the index date and after 1 year of follow-up and to be persistent on therapy for 1 year may have introduced potential selection bias in favor of patients who are more actively managed and/or for whom treatment is effective. Claims data are subject to miscoding or misclassification of diagnosis codes. It was also assumed that patients use their treatment as prescribed based on prescription fill dates and recorded days of supply. Additionally, this study did not include an evaluation of the impact of weight loss on the incidence of obesity-related complications, as this analysis would require longer-term follow-up (over multiple years) that is not currently possible given the relatively recent approval of these medications and may require laboratory data; however, this is an important topic for future research. Lastly, the study’s patient identification window began at the initial availability of semaglutide 2.4 mg; patients who initiated semaglutide 2.4 mg or tirzepatide at an earlier stage of availability may not be representative of the general population of patients who are treated with these medications today. Notably, tirzepatide (Zepbound) was not approved for weight management in patients with overweight or obesity until shortly before the patient-identification window closed, resulting in most patients in the tirzepatide cohort receiving Mounjaro, which was assumed to be used off-label for chronic weight management in the absence of T2DM. More recent data and larger sample sizes are necessary to study the real-world, long-term weight loss associated with Zepbound specifically.
Conclusions
In patients with overweight or obesity and without T2DM, treatment with semaglutide 2.4 mg and tirzepatide was associated with 14.1% and 16.5% weight loss, respectively, after a 1-year follow-up period, indicating the effectiveness of these therapies in routine clinical practice in the US. Both treatments demonstrated clinically meaningful weight loss. The large sample size and demographic data enhance the generalizability of the results to the broader population and reflect a real-world context that aligns with the public health importance of addressing obesity. This study underscores semaglutide 2.4 mg and tirzepatide as important treatment options for managing obesity and its related conditions.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
Medical Writing/Editorial Assistance
Editorial and medical writing support were provided by Jessica A. Weaver, PhD, CMPP™, of Lumanity Communications Inc., and were funded by Novo Nordisk Inc.
Author Contribution
Carmen D. Ng, Victoria Divino, Julia Wang, Joshua C. Toliver, and Marcio Buss contributed to conceptualization, methodology, data interpretation, and writing – review and editing. Carmen D. Ng and Marcio Buss also contributed to the formal analysis.
Funding
This study was sponsored by Novo Nordisk Inc. Novo Nordisk Inc. also funded the journal’s Rapid Service Fee and Open Access Fee.
Data Availability
All data that support the conclusions of these analyses are presented in this research brief or the supporting information. Details of additional data can be obtained from the corresponding author upon reasonable request.
Declarations
Conflict of Interest
Carmen D. Ng, Victoria Divino, Julia Wang, Joshua C. Toliver, and Marcio Buss are employees and shareholders of Novo Nordisk Inc.
Ethical Approval
This study was conducted in accordance with relevant guidelines and regulations, including the principals of the Declaration of Helsinki of 1964 and its later amendments. This study used only de-identified patient records and did not involve the collection, use, or transmittal of individually identifiable data. The Department of Health and Human Services does not consider analysis of de-identified secondary data to meet the definition for human subject research. Therefore, this study was exempt from federal regulations covering human subject research and did not require institutional review board review. This is as per exemption (d)4 from 45 CFR 46.104. Novo Nordisk Inc. has a data access license to the Komodo Health database.
Footnotes
Prior Presentation: This work was presented in part as a poster at the Endocrine Society (ENDO) Annual Meeting held July 12–15, 2025, in San Francisco, CA, USA.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
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Supplementary Materials
Data Availability Statement
All data that support the conclusions of these analyses are presented in this research brief or the supporting information. Details of additional data can be obtained from the corresponding author upon reasonable request.