Tirzepatide Demonstrates Superiority for Weight Loss Compared With Semaglutide

Tirzepatide (Zepbound; Eli Lilly and Company) demonstrated 47% greater relative weight loss compared to semaglutide (Wegovy; Novo Nordisk) in the SURMOUNT-5 (NCT05822830) phase 3b open-label trial. The full results will be published in a peer-reviewed journal and presented at a medical meeting next year as the company continues to evaluate the full results.¹

Tirzepatide, GLP-1, Semaglutide, Weight Loss | Image Credit: © zimmytws | 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. "We are thrilled that today's findings showed the superior weight loss of Zepbound, which helped patients achieve 47% more relative weight loss compared to Wegovy. Zepbound is in a class of its own as the only FDA-approved dual [gastric inhibitory polypeptide] and [glucagon-like peptide]-1 receptor agonist obesity medication, and it's changing how millions of people manage this chronic disease.”¹

The SURMOUNT-5 study evaluated the safety and efficacy of tirzepatide compared with semaglutide over a period of approximately 74 weeks in adults with obesity or overweight with weight-related comorbidities without type 2 diabetes. Individuals included in the study had a body mass index (BMI) of 30 kg/m² or greater and were previously diagnosed with at least 1 comorbidity including hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. Further, the individuals had a history of at least 1 unsuccessful dietary effort to lose body weight. Individuals with diabetes, a history of pancreatitis, or history of major depressive disorder or other severe psychiatric disorder within the last 2 years were excluded.²

There was a total of 751 individuals enrolled across the US and Puerto Rico, and treatment was randomized 1:1. Individuals received the maximum tolerated dose of tirzepatide at 10 mg or 15 mg or semaglutide at 1.7 mg or 2.4 mg. Investigators administered the drugs subcutaneously, with a primary outcome of percent change from baseline in body weight to week 72 and secondary end points of percentage of individuals who achieve a 10% body weight reduction or greater, 15% reduction or greater, 20% reduction or greater, 25% reduction or greater, and a 30% reduction or greater at 72 weeks. Further, secondary outcomes included change from baseline in waist circumference, change from baseline in BMI, and percent change from baseline in body weight comparing tirzepatide 15 mg to semaglutide 2.4 mg at week 74.²

On average, investigators found that tirzepatide had a superior weight loss of 20.2% compared with 13.7% for semaglutide, and tirzepatide was superior to semaglutide on the primary end points and all 5 key secondary end points for this patient population. Approximately 31.6% of patients taking tirzepatide achieved at least 25% body weight loss compared with 16.1% of those on semaglutide.¹

For safety, tirzepatide was similar to previously reported data from the other SURMOUNT trials, with the most commonly reported adverse events including gastrointestinal events that were generally mild to moderate in severity. Semaglutide had similar results with gastrointestinal events being the most common.¹

REFERENCES

1. Lilly's Zepbound (tirzepatide) superior to Wegovy (semaglutide) in head-to-head trial showing an average weight loss of 20.2% vs. 13.7%. News release. Eli Lilly. December 4, 2024. Accessed December 4, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head

2. A Study of Tirzepatide (LY3298176) in Participants With Obesity or Overweight With Weight Related Comorbidities (SURMOUNT-5). ClinicalTrials.gov ID: NCT05822830. Updated August 28, 2024. Accessed December 4, 2024. https://clinicaltrials.gov/study/NCT05822830