Tirzepatide outperforms semaglutide in weight loss for overweight and obese adults

In a recent study published in JAMA Internal Medicine, researchers compared the weight loss and gastrointestinal adverse event rates for obese or overweight adults undergoing treatment with the medications semaglutide or tirzepatide, which are both currently labeled for clinical use for type 2 diabetes.

Study: Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. Image Credit: New Africa / ShutterstockStudy: Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. Image Credit: New Africa / Shutterstock


Obese or overweight individuals are generally at a higher risk of cardiovascular and metabolic diseases and have higher morbidity and mortality rates in comparison to individuals within the normal weight range. Historically, very few pharmacological treatments or anti-obesity medications have been developed for weight loss, and the few that exist have a high rate of adverse reactions and show only modest results in weight loss.

However, recent randomized clinical trials have reported significant weight loss associated with newer medications such as semaglutide, which is a glucagon-like peptide (GLP) 1 receptor agonist, and tirzepatide, also a or GLP-1 receptor agonist and a gastric inhibitory polypeptide agonist, among obese individuals irrespective of type 2 diabetes status.

Both these medications are labeled for clinical use for type 2 diabetes, and while data from randomized control trials suggest that tirzepatide results in more significant weight loss than semaglutide in type 2 diabetes patients, comparisons of weight loss results for both medications from overweight or obese individuals in a clinical setting are lacking.

About the study

The present study aimed to compare the on-treatment weight loss due to semaglutide and tirzepatide among overweight or obese individuals in a clinical population, as it is unclear whether semaglutide and tirzepatide treatments in the clinical setting reflect the weight loss observed in randomized clinical trials.

The researchers believe that because both medications are expensive, and most health insurance companies will not cover these medications for obese or overweight individuals who do not have type 2 diabetes, the adherence to these treatments might vary in the clinical setting.

Overweight and obese individuals who had just begun semaglutide or tirzepatide treatments were enrolled in the study, irrespective of type 2 diabetes status. The day of the administration of the first dose of semaglutide or tirzepatide was considered the study index date. The study only included adult participants for whom baseline weight measurements were available and who had regular healthcare interactions.

Follow-ups to monitor weight loss or adverse events occurred until the administration censored the treatment, therapy was discontinued, treatment was switched, or the study ended, whichever occurred first.

The study used electronic health record data consisting of demographic information, diagnoses, medication prescription information, vital measurements, laboratory test results, and surgical procedures for the analyses. Additional information on social drivers of health and medication dispensing information was also used for the study.

Tirzepatide is available under the brand name of Mounjaro, produced by Eli Lilly, while Ozempic, produced by Novo Nordisk, is the brand name for semaglutide. The dosage was based on what was recommended by the brand — 5.0 mg of tirzepatide or 0.5 mg of semaglutide. Both medications were labeled for type 2 diabetes at the time of the study.

Additionally, the patient’s comorbidities and covariates were considered during the analyses. Comorbidities included insulin prescription or use and a hemoglobin A1c (HbA1c) level greater than 7.5% in the past two years. The primary outcome of interest was weight loss on treatment. Secondary outcomes included safety outcomes investigated in the study, which included gastrointestinal adverse events such as pancreatitis, gastroparesis, cholelithiasis, and bowel obstruction.


The findings suggested that tirzepatide treatment in a clinical population resulted in significantly greater weight loss in overweight or obese individuals than semaglutide treatment, irrespective of the occurrence of type 2 diabetes.

The study found that overweight or obese individuals undergoing tirzepatide treatment had a higher probability of achieving equal to or greater than 5%, 10%, and 15% weight loss at three, six, and 12 months, respectively, as compared to individuals who were getting treated with semaglutide.

Furthermore, the researchers found no significant difference in terms of gastrointestinal adverse effects between semaglutide and tirzepatide treatment. These findings are consistent with what was observed during the randomized control trials for both medications and the results from placebo-controlled trials, which also reported more significant weight loss associated with tirzepatide treatment as compared to semaglutide treatment, irrespective of type 2 diabetes status.


Overall, the study showed that treatment of obesity or overweight with tirzepatide achieved greater weight loss than semaglutide treatment, regardless of type 2 diabetes status. Furthermore, no major differences were observed in the gastrointestinal adverse effect risk between the two treatments.

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