Eli Lilly Announces Positive Phase 3b SURMOUNT-5 Trial Results for Tirzepatide in Obesity Treatment, Published in The New England Journal of Medicine

Recently, Eli Lilly and Company announced the detailed results of the SURMOUNT-5 trial. The analysis showed that at week 72,Its glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide reached the primary endpoint and all five key secondary endpoints.,and showed superiority over the active comparator throughout the trial. The results were presented at the 32nd European Congress on Obesity and simultaneously published in The New England Journal of Medicine.

Obesity is a chronic, progressive, and recurrent disease caused by a combination of genetic, environmental, and social factors, and is not merely a problem of lifestyle habits. With a sharp increase in the number of obese patients globally, it is estimated that by 2030, more than 2.9 billion adults worldwide will be overweight or obese; in China, this proportion may reach as high as 65.3%, with the resulting medical burden expected to account for 21.5% of the total national healthcare expenditure.Obesity can lead to more than 200 health complications, including type 2 diabetes, hypertension, coronary heart disease, and various cancers, with approximately 89% of obese patients having at least one chronic complication.，seriously affecting the patient's physical function and mental health.

Although lifestyle and behavioral changes are the foundation of long-term weight management, simply "eating less and moving more" often fails to achieve effective and sustained weight loss. Therefore, scientific medical interventions are gaining increasing attention, particularly in the realm of weight-loss medications.In recent years, the emergence of novel weight-loss drugs has not only significantly reduced patients' weight but also brought multiple health benefits in metabolism, cardiovascular and renal aspects.In addition, the early initiation of medical intervention and long-term continuous management can more effectively prevent weight rebound and reduce the negative impact of obesity on patients' quality of life and lifespan.

The recently announced SURMOUNT-5 is an open-label Phase 3b clinical trial designed to evaluate the efficacy and safety of tirzepatide compared to the GLP-1 receptor agonist semaglutide in overweight adults with obesity or at least one comorbidity (such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) who do not have diabetes.

The trial enrolled approximately 751 patients, who were randomly assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the active comparator (1.7 mg or 2.4 mg). In the tirzepatide group, 89.3% of participants received at least one dose of 15 mg, while in the active comparator group, 92.8% of participants received at least one dose of 2.4 mg. The primary endpoint of the study was to demonstrate the superiority of tirzepatide over the active comparator in terms of percentage reduction in body weight from baseline at week 72.

Analysis shows that the trial met the primary endpoint.Tirzepatide achieved a 1.47-fold relative weight loss compared to the active control drug.Based on the study data of estimands for the treatment strategy, at Week 72,Tirzepatide achieved an average weight loss of 20.2% (95% CI: 21.4-19.1), compared to 13.7% (95% CI: 14.9-12.6) for the active comparator drug.The tirzepatide group lost an average of 22.8 kg, while the active control drug group lost an average of 15.0 kg.

In the key secondary endpoints of the study, tirzepatide was superior to the active comparator across all weight loss targets. The proportion of participants in the tirzepatide group achieving ≥15% weight loss reached 64.6%, compared to 40.1% in the active comparator group. Additionally,The average waist circumference reduction in the tirzepatide group was 18.4 cm (95% CI: 19.6-17.2), compared to 13.0 cm (95% CI: 14.3-11.7) in the active comparator group.

In the SURMOUNT-5 study, the overall safety profile of tirzepatide was consistent with previous SURMOUNT studies. During the clinical trial period, the most common adverse events were mild to moderate gastrointestinal-related adverse events. The proportion of participants who discontinued treatment due to adverse events was 6.1% in the tirzepatide group and 8.0% in the active comparator group, but the study was not able to compare the differences in safety and tolerability between tirzepatide and the active comparator.

Tirzepatide is a once-weekly injectable GIP/GLP-1 dual receptor agonist.Tirzepatide is a single-molecule peptide that can simultaneously activate the natural GIP and GLP-1 receptors. Both receptors are expressed in key areas of the brain that regulate appetite. Tirzepatide may reduce energy intake by influencing appetite. Studies on the clinical outcomes (MMO) of tirzepatide in patients with chronic kidney disease (CKD) and obesity are currently underway.

References:

[1] Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, Das S, Lee CJ, Glass LC, Senyucel C, Dunn JP; SURMOUNT-5 Trial Investigators. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025 May 11. doi: 10.1056/NEJMoa2416394. Epub ahead of print. PMID: 40353578.

[2] Head-to-Head Study: Tirzepatide Shows Superiority Over Semaglutide in Weight Loss and Waist Circumference Reduction. Retrieved May 12, 2025 from https://mp.weixin.qq.com/s/ZQ6TWHbNdNIChNWWL7y8Tg

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