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.
Keywords: Clinical practice; Obesity; Overweight; Real-world evidence; Semaglutide; Tirzepatide; Weight loss; Weight management.
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.
© 2025. The Author(s).