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Zepbound Shows Superior Weight Loss Compared to Wegovy in SURMOUNT-5 Trial
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Key Takeaways
- Tirzepatide achieved a 20.2% average weight loss, surpassing semaglutide's 13.7%, with a 47% greater relative weight loss.
- The trial included 751 adults with obesity or overweight and at least one comorbidity, demonstrating tirzepatide's superiority in weight reduction.
Tirzepatide outperforms semaglutide in weight loss, achieving an average reduction of 20.2% in a pivotal trial for obesity management.
Tirzepatide (Zepbound; Eli Lilly and Company) demonstrated superior weight loss over semaglutide (Wegovy; Novo Nordisk) in a phase 3b open-label trial, SURMOUNT-5 (NCT05822830), that evaluated the safety and efficacy of the 2 glucagon-like peptide-1 (GLP-1) receptor agonists.1 The results build on December’s announcement, demonstrating that tirzepatide led to more weight loss in adults living with obesity or overweight with at least 1 weight-related medical problem without diabetes.2
Injection pen for Weight loss medication Zepbound - Tirzepatide is an antidiabetic medication used for the treatment of type 2 diabetes and weight loss. New York, NY, USA - Jan 10 - Image credit: Douglas | stock.adobe.com
"Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice," Leonard C. Glass, MD, FACE, senior vice president of global medical affairs at Lilly Cardiometabolic Health, said in a news release.2
Weight Reduction with Tirzepatide Across Key End Points
The 72-week, multicenter, randomized, open-label phase 3 trial included adults with obesity or overweight who did not have diabetes with at least 1 comorbidity, including hypertension, dyslipidemia, obstructive sleep apnea (OSA), or a cardiovascular disease. The primary objective of the study was to demonstrate superiority among individuals treated with tirzepatide in percent change from baseline in body weight at study completion compared with semaglutide.1
A total of 751 individuals were included and were randomly assigned on a 1:1 ratio to receive a maximum tolerated dose of tirzepatide (10 mg or 15 mg) or semaglutide (1.7 mg or 2.4 mg). Approximately 89.3% of individuals received at least one 15-mg dose of tirzepatide, and 92.8% received at least one 2.4-mg dose of semaglutide.1
The results demonstrated that at 72 weeks, tirzepatide met its primary end point and all 5 key secondary end points, including superiority across all weight reduction targets, with 64.6% of individuals treated with tirzepatide achieving nearly 15.0% weight loss compared to 40.1% on semaglutide. Additionally, individuals treated with tirzepatide achieved a superior waist circumference reduction of 7.2 inches, compared with a 5.1-inch reduction in the semaglutide group.
Shifting to the primary end point, individuals treated with tirzepatide experienced an average weight loss of 20.2%, which was significantly greater than the 13.7% average weight loss seen with semaglutide, representing a 47% greater relative weight loss. On average, individuals using tirzepatide lost 50.3 lbs, whereas those on semaglutide lost an average of 33.1 lbs.1
"In the SURMOUNT-5 trial, Zepbound demonstrated a significantly higher magnitude of weight reduction compared to Wegovy across all comparisons," Glass said in a news release. "These data confirm Zepbound as a leading treatment option for people living with obesity and equip health care providers with critical insights to make well-informed treatment decisions as part of a comprehensive obesity care plan."1
The study authors noted that the safety profile in the SURMOUNT-5 trial was similar to what was observed in earlier SURMOUNT studies. Most of the reported adverse effects were gastrointestinal and were typically mild to moderate.1
In the study, 6.1% of individuals in the tirzepatide group stopped treatment due to adverse events, while 8.0% of individuals on semaglutide discontinued for the same reason. However, the study was not designed to directly compare the safety of how well tirzepatide and semaglutide were tolerated, the study authors noted.1
Tirzepatide Mechanism of Action
Tirzepatide is administered once weekly, and it works by activating both glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, which are natural hormones involved in appetite control in the brain. Marked as the first and only approved dual GIP and GLP-1 receptor agonists, the medication helps decrease calorie intake, likely by affecting appetite, in combination with diet and exercise.1
In the US, tirzepatide has been approved by the FDA as Mounjaro (Eli Lilly and Company) for type 2 diabetes in May 2022 and as Zepbound for obesity and excess weight with related medical issues in November 2023. However, outside of the US, Mounjaro is also marketed for weight management for certain adults.1
"Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before," Louis J. Aronne, MD, FACP, DABOM, principal investigator of SURMOUNT-5, said in a news release. "The SURMOUNT-5 head-to-head results demonstrated tirzepatide led to greater weight reduction compared to semaglutide, providing further evidence to support tirzepatide as an effective option for obesity management."1
