A new top-to-head study reveals that the shooting reaches 47% more weight loss than semaglutide in people with obesity but without diabetes, highlighting its higher efficiency and cardiometabolic advantages.
A new revolutionary study has revealed that shooting leads to significantly greater weight loss than semaglutide in people living with obesity but without diabetes. During 72 weeks, participants taking firing lost an average of 20.2% of their body weight. It is a reduction of 47% higher compared to the average weight loss of 13.7% observed with the semaglutide.
These results were presented at the European Congress in 2025 on obesity in Malaga, Spain, and published in the New England Journal of Medicine. The study was led by Dr. Louis J. Aronne, director of the full weight control center of Weill Cornell Medicine in New York.
Tirzepatid and semaglutide are powerful drugs used to help manage obesity. However, this is the first direct comparison of the two in people who do not have type 2 diabetes. Research was sponsored by Eli Lilly & Company, The Makers of Tirzepatide.
In the trial, 751 adults with obesity but no diabetes diagnosis was assigned to chance to receive either shooting (10 mg or 15 mg) or semaglutide (at 1.7 mg or 2.4 mg). The two drugs were given as injections once a week for a total of 72 weeks.
The average participant was about 45 years old. About two thirds were women and just over three -quarters were white. Most have lived with obesity for about 16 years. At the start of the study, their average body weight was 113 kilograms, with an average body mass index (
“Data-Gt-translate-attrattes =” ({“attribute =” “tabindex =” 0 “role =” link “> bmi) 39.4 and an average size of 118 centimeters. About half of the group also had two health problems related to obesity or more.
Efficiency results: weight loss and size reduction
The main evaluation criterion at week 72 was the percentage of weight variation compared to the basic line. Key secondary evaluation criteria included weight reduction objectives of at least 10%, 15%, 20%and 25%, and the variation in the size of the basic line at week 72.
The key inclusion criteria for this test included 18 years or more, a body mass index (BMI) of 30 kg / m2 or more, or a BMI of 27 kg / m2 or more and at least a complication linked to predefined obesity (hypertension, dyslipidemia, obstructive sleep apnea, or
“Data-Gt-translate-attributes =” ({“attribute =” “tabindex =” 0 “role =” link “> cardiovascular disease), and experience at least an unsuccessful food effort for weight reduction. The main exclusion criteria included the diagnosis of diabetes, the previous or planned surgical treatment for obesity, or if within 90 days before screening, they had received treatment with a drug reduction or a GLP-1 receptor agonist, or a change in body weight of more than 5 kg.
The average weight variation at week 72 was -20.2% with shooting and -13.7% with semaglutide -therefore 47% higher for shooting. The average decrease in the waist was -18.4 cm with shooting and -13.0 cm with semaglutide -therefore 42% higher for shooting. Participants treated with Tizepatide were 30%, 60%, 80%and twice as likely to reach weight reduction targets of 10%, 15%, 20%and 25%, respectively, compared to semaglutide. A total of 19.7% of the participants of the Tirzepatid group had a reduction in body weight of at least 30% (an exploratory end point) compared to 6.9% of those of the semaglutide group, which indicated that the probability of reaching this target of weight reduction with the shooting was 2.8 times higher than with the Semaglutide.
The most common adverse events for the two treatments in the study were gastrointestinal, and most were light to moderate gravity, occurring mainly during dose climbing.
Weight reduction was about 6% less in men than women for two treatments and explains the slightly lower weight reduction in the current trial compared to previous trials. The current test had a higher proportion of men at 35%, in particular compared to non-diabetes tests, which included 19 to 26% of men. Current results align with the results reported for surmount and step programs as well as recent evidence of the real world demonstrating a higher weight reduction with Tizepatid than semaglutide.
Action mechanism: why the shooting can be superior
Dr. Aronne explains: “Although it is a single molecule, the shooting active pharmacologically active two metabolic receptors, GIP and GLP-1, which have both an expression and an overlapping and non-picking function. This activity with double agonism of shooting can contribute to the greater weight reduction observed with the shooting than with the semaglutide, a mono-use monoagonist.
The results show that as weight reduction increased, there were larger improvements in cardiometabolic risk factors, including blood pressure and blood and sugar levels, the two treatments in accordance with previous reports. The authors explain that, although some patients do not necessarily require higher weight reduction amplitudes to see clinical advantages, these results support the clinical relevance of this study, because the majority of participants receiving shooting (65%) were able to reach at least 15% weight loss against 40% for semaglutide; And almost a third (32%) have reached at least 25% weight reductions with shooting compared to 16% with semaglutide.
They also explain that the additional 5.4 cm additional reduction in the waist tour with the shooting compared to the semaglutide is also clinically relevant. In a large analysis grouped together in the waist and mortality, each increase of 5 cm of the waist Tour predicts a 7% increase in mortality in men and an increase of 9% in women. In alignment with this data, the directives published highlighted the importance of treating patients with abdominal obesity and aiming for a reduction of at least 4 cm.
The essay has certain strengths and limits. A force is the diversity of participants because 19% reported an American black African breed and 26% reported a Hispanic or Latino ethnic, representative of the populations in the United States living with obesity. The approach of the test on the use of the maximum tolerated dose for the two treatments addresses a potentially more significant real question, compared to a fixed dose approach. However, a limitation is that the trial was not blinded, which means that the participants knew which medication and the dose they received. However, the authors explain the consistency of the current results with tests previously blind supports their generalization.
Dr. Artonne concludes: “Our study shows that the shooting treatment was higher than the semaglutide with regard to the reduction in body weight and the waist tower.”
Reference: “Tirzepatid compared to the semaglutide for the treatment of obesity” of Louis J. Aronne, Deborah Bade Horn, Carel W. Le Roux, Wayne Ho, Beverly L. Falcon, Elisa Gomez Valderas, Sagar Das, Clare J. Lee, Leonard C. Glass, Cagri Senyucel and Julia P. Dunn, 11 May25, Glass, Cagri Senyucel and Julia P. Dunn, 11 May 2025 New England Journal of Medicine.
DOI: 10.1056 / Nejmoa2416394
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