By Don Tracy, Associate Editor

JAMA study aims to discover how weight loss differs between patients receiving tirzepatide compared with semaglutide among a clinical population of overweight of obese adults.
Tirzepatide and semaglutide are both GLP-1 agonists that have demonstrated the ability to offer significant weight reduction in patients with obesity, with or without type 2 diabetes (T2D). There are currently no real-world data comparing the effectiveness of the two in treating overweight or obese populations.
In a cohort study recently published in JAMA Internal Medicine, researchers set out to provide a head-to-head comparison of these medications in a real-world clinical setting, focusing on weight loss outcomes and gastrointestinal adverse events (AEs). The study included 18,386 patients who were new users of tirzepatide or semaglutide with overweight or obesity, regardless of T2D status. Additionally, patients were selected based on their electronic health records data and propensity-score matched to ensure comparability. In most cases, patients achieved notable weight loss within a year of treatment.
The study, which implemented a subset of Truveta data, included structured information on demographics, encounters, diagnoses, vital signs, medication requests, laboratory and diagnostic tests and results, and procedures. According to the researchers, only patients with a complete negative history of GLP-1 receptor agonist use were enrolled in the study. In order to improve outcome observability, the researchers also limited the analysis to patients with regular interactions with the health care system during the year prior to their index date. The study was conducted between May 1, 2022, and September 30, 2023.
Results found that patients receiving tirzepatide were more likely to achieve substantial weight loss compared to those on semaglutide. Hazard ratios set for achieving 5%, 10%, and 15% weight loss were also much higher for patients treated with tirzepatide. Full results at the one-year mark are as follows:
5% weight loss: 81.8% for tirzepatide compared to 66.5% for semaglutide
10% weight loss: 62.1% for tirzepatide compared to 37.1% for semaglutide
15% weight loss: 42.3% for tirzepatide compared to 18.1% for semaglutide
Additionally, tirzepatide users saw greater reductions in body weight at 3, 6, and 12 months, with differences of -2.4%, -4.3%, and -6.9%, respectively.1
“Findings in this study are broadly consistent with existing evidence from RCTs. Among placebo-controlled trials of patients with overweight or obesity, treatment with tirzepatide at 10 mg per week resulted in 82% and 96% of individuals with and without T2D achieving 5% or more weight loss by 72 weeks, respectively (efficacy estimands),” reported the authors of the study. “Among similarly designed placebo-controlled trials, treatment with semaglutide at 2.4 mg per week resulted in 73% and 92% of individuals with and without T2D achieving 5% or greater body weight by 68 weeks, respectively (efficacy estimands). While data from head-to-head trials are more limited, a single study that evaluated the glucose-lowering effect of tirzepatide (5 mg per week) compared with semaglutide (1 mg per week) in patients with T2D found that 5% weight loss was achieved by 69% and 58%, respectively. Importantly, a trial comparing tirzepatide to semaglutide in patients with overweight or obesity, but without T2D is underway (SURMOUNT-5, NCT05822830); the results, however, are not expected until late 2024.”
The researchers also noted that discontinuation rates were high for both medications, with over half of patients stopping treatment within the study period. However, adherence and effectiveness of tirzepatide was found to be significantly higher.
Despite the study data offering a clear result, the researchers acknowledged that the data were collected during routine clinical care, suggesting that AEs were likely to be underreported. Further, weight changes were only ascertained only when patients return for visits, resulting in delayed observed event times.1
“In this large, propensity-matched, cohort study, individuals with overweight or obesity treated with tirzepatide were significantly more likely to achieve clinically meaningful weight loss and larger reductions in body weight compared with those treated with semaglutide,” concluded the study authors. “Consistent treatment effect estimates were observed in subgroups with and without T2D. Future work is needed to compare the effect of tirzepatide and semaglutide on other key end points (eg, reduction in major adverse cardiovascular events).”