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Semaglutide and Tirzepatide

Study Compares Effects of ‘Weight Loss Injections’ – This Compound Prevails

A study compared the active ingredients in weight-loss injections.
A comparison of the so-called "weight loss injections" reveals that one active ingredient is significantly more effective for weight reduction. Photo: Getty Images
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October 15, 2025, 11:00 am | Read time: 5 minutes

Not only celebrities are increasingly turning to the so-called “weight loss injection” to shed pounds. Now, two studies show that there are differences in the effectiveness of various providers. A particular active ingredient stands out and leads to especially rapid weight reduction, according to the research findings.

As is often the case, the media hype around the so-called “weight loss injection” was sparked by celebrities. In this instance, stars like Robbie Williams, Sharon Osbourne, and John Goodman made headlines when they appeared significantly slimmer in public in early 2024. The reason: They used the drug Ozempic, which is injected, hence the colloquial term weight loss injection. The medication belongs to the GLP-1 receptor agonists and was originally approved for treating Type 2 diabetes. Doctors now also prescribe it for severe obesity. In a comparison of weight loss injections, researchers now provide evidence that one is more effective for weight loss.

Weight Loss Injections in Active Ingredient Comparison

The currently popular weight loss injections typically use two active ingredients: Tirzepatide or Semaglutide. Both are GLP-1 receptor agonists used to treat Type 2 diabetes and obesity. The difference between the two is that Tirzepatide also acts as a GIP receptor agonist. As a so-called dual agonist, it works on both GIP and GLP-1 receptors, enhancing its effectiveness. Both glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) lead to a reduction in blood sugar levels, hunger, and ultimately weight loss.1

  • Tirzepatide is known under medication names such as Mounjaro and Zepbound.
  • Semaglutide is used in medications Wegovy and Ozempic.

Although both active ingredients are very effective for weight reduction, a recent study shows a clear “winner.”

How the Study Was Conducted

In a recent study, researchers examined and compared the effects of Tirzepatide and Semaglutide in adults with obesity—but without Type 2 diabetes. The study focused not only on effectiveness but also on the tolerability and safety of the medications. The study was first published in the renowned “The New England Journal of Medicine.”2

For the study, 750 adults with severe obesity were recruited. They either had a body mass index (BMI) of at least 30 without health issues or a BMI higher than 27 with complications such as high blood pressure, elevated cholesterol levels, obstructive sleep apnea, or cardiovascular diseases. More facts about the participants:

  • The average age was 44.7 years
  • 64.7 percent were female
  • The average starting weight was 113 kilograms
  • The average BMI was 39.4
  • The average waist circumference was 118.3 centimeters

Participants were randomly divided into two equal groups. One group received a weekly injection of Tirzepatide (10 or 15 milligrams) for 72 weeks. The other group received Semaglutide (1.7 or 2.4 milligrams) over the same period. Both groups started with a low dose of 2.5 milligrams for Tirzepatide and 0.25 milligrams for Semaglutide, gradually increasing to the maximum tolerable dose.

All participants also received nutritional counseling and tips on physical activity. During the 72-week study period, weight and waist circumference were regularly measured. Tolerability was monitored through adverse side effects such as digestive issues and reactions at the injection site. Participants who experienced severe side effects could reduce the dose or stop the injections altogether but were still observed until the study’s end.

FITBOOK expert, cardiologist Dr. Schneeweis, explains heart failure in the following video:

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There Was a Clear “Winner” in the Weight Loss Injection Comparison

The data analysis revealed a clear result: After 72 weeks, participants treated with Tirzepatide lost an average of 20.2 percent of their body weight. Those treated with Semaglutide lost only 13.7 percent. This corresponds to an average weight reduction of about 22.8 kilograms with Tirzepatide and 15 kilograms with Semaglutide over 72 weeks.

Other figures also clearly favor Tirzepatide:

  • With Tirzepatide, 81.6 percent of participants achieved a weight loss of at least 10 percent
  • With Semaglutide, only 60.5 percent lost more than 10 percent of their body weight
  • Almost 32 percent of Tirzepatide users lost a quarter or more of their weight. With Semaglutide, it was around 16 percent.
  • Tirzepatide was also more effective in reducing waist circumference, which was on average 18.4 centimeters less than with Semaglutide (13.0 centimeters).

The study also showed: The higher the weight loss (for example, more than 20 percent), the better the blood pressure values and other health risk factors. Another interesting aspect: Women in both test groups lost about six percent more weight on average than men.

There were no surprises with the side effects. As already known, high doses mainly led to digestive tract issues, including nausea, diarrhea, constipation, and vomiting, which were mostly mild to moderate.

Limitations of the Study

Although the comparison of weight loss injections clearly favors the active ingredient Tirzepatide, there is a small catch: The study was funded by the pharmaceutical company Eli Lilly, which happens to be the manufacturer of Tirzepatide. However, this is not the first study to suggest the higher effectiveness of Tirzepatide.

As early as 2024, Tirzepatide and Semaglutide were directly compared in the treatment of obesity.3 In this study with 18,386 participants, the researchers concluded that Tirzepatide led to greater weight loss than Semaglutide in overweight individuals. The side effects were comparable for both medications.

  • 81.8 percent of participants with Tirzepatide had a weight loss of at least 5 percent – with Semaglutide, it was 66.5.
  • 62.1 percent of participants had a weight loss of at least 10 percent – with Semaglutide, it was 37.1.
  • 42.3 percent had a weight loss of at least 15 percent – with Semaglutide, it was 18.1.

Yet, the study authors emphasized that further research is needed to compare weight loss injections to better explore the differences between the two active ingredients, such as in terms of reducing cardiovascular diseases. 

This article is a machine translation of the original German version of FITBOOK and has been reviewed for accuracy and quality by a native speaker. For feedback, please contact us at info@fitbook.de.

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