Title: Real-World Comparative Effectiveness of Semaglutide 2.4 mg vs. Anti-Obesity Medications: A Pragmatic Clinical Study in a Multiple Employer Setting
Introduction Obesity has become a significant public health concern, contributing to various comorbidities and decreased quality of life. While randomized clinical trials provide valuable efficacy data, pragmatic studies that bridge the gap between controlled trials and real-world clinical practice are essential for evaluating the effectiveness of interventions in diverse settings. This article presents an overview of a pragmatic clinical study conducted in a multiple employer setting in the US, aiming to compare the real-world effectiveness of semaglutide 2.4 mg, a novel anti-obesity medication, with existing commercially available Anti-Obesity Medications (AOMs).
Study Design and Rationale The study design is interventional, randomized, parallel-group, open-label, and active comparator-controlled. It follows a pragmatic approach, capturing real-world effectiveness data while maintaining key elements of clinical study design, including treatment randomization. The study population consists of approximately 28,000 employees from two US-based employers representing diverse demographics and job functions. The study aims to inform healthcare decision-makers, including employers, clinicians, payers, and policy makers, about comprehensive approaches to obesity care management for employees.
Objectives and Endpoints The primary objective of the study is to demonstrate the superiority of semaglutide 2.4 mg compared to Other AOMs in achieving a ≥10.0% body weight reduction from baseline in adults with obesity. The primary endpoint is the proportion of participants achieving this weight reduction at week 52. Secondary objectives include assessing the relative change in body weight from baseline and the change in physical functioning.
Estimand and Clinical Question of Interest The primary estimand focuses on measuring the effectiveness of semaglutide 2.4 mg versus Other AOMs as an adjunct to lifestyle management in employed adults living with obesity in the US. It considers the number of participants achieving ≥10% body weight loss at week 52, irrespective of adherence to randomized treatment and initiation of other anti-obesity therapies. This estimand accounts for safety and efficacy aspects and aligns with clinical practice in an employer setting.
Study Implementation and Intervention The study is coordinated by Loma Linda University School of Public Health, with clinical investigators managing participant identification, consent, and treatment based on their clinical judgment and routine practice. Participants are randomized 1:1 to receive either semaglutide 2.4 mg (Wegovy®) or one of the Other AOMs. The choice of Other AOMs is at the discretion of the investigator and aligned with prescribing information. Treatment adjustments are made according to clinical judgment and prescribing labels.
Study Duration and Participant Characteristics The study duration for each participant is approximately one year. A total of 600 participants will be screened to achieve 500 participants randomized to semaglutide 2.4 mg or Other AOMs. Key inclusion criteria include a BMI ≥30.0 kg/m2 and employment by one of the selected employers at randomization. Key exclusion criteria involve hypersensitivity or contraindications to the study medications, pregnancy or intentions to become pregnant, history of diabetes mellitus, and other factors jeopardizing participant safety or compliance with the protocol.
Implications and Conclusion This pragmatic clinical study conducted in a multiple employer setting in the US aims to generate real-world evidence regarding the comparative effectiveness of semaglutide 2.4 mg and existing AOMs for obesity management. The study’s outcomes will provide valuable insights for healthcare decision-makers in optimizing obesity care management strategies for employees. By considering both safety and efficacy, the study addresses the clinical question of interest while aligning with real-world clinical practice in an employer setting.
In conclusion, this study contributes to closing the gap between controlled trials and real-world effectiveness data for anti-obesity medications. By evaluating the relative weight reduction and physical functioning outcomes of semaglutide 2.4 mg compared to Other AOMs in a multiple employer setting, this research aims to enhance the understanding of comprehensive obesity care management approaches.
Keywords: obesity, semaglutide, anti-obesity medications, pragmatic study, comparative effectiveness, real-world evidence, multiple employer setting.
References:
[1] Pragmatic trials – guides and information. National Institute for Health Research. https://www.nihr.ac.uk/documents/pragmatic-trials-guides-and-information/14573. Accessed June 27, 2023.
[2] Glasgow RE, et al. Pragmatic measures: what they are and why we need them. Am J Prev Med. 2013;45(2):237-243.
[3] ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf. Accessed June 27, 2023.