Tirzepatide vs Semaglutide: Superior Weight Loss

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

Background

Obese or overweight people are more likely to develop cardiovascular and metabolic disorders, as well as having greater morbidity and mortality rates, than people who are normal weight. Historically, very few pharmacological treatments or anti-obesity drugs have been created for weight loss, and those that do exist have a high rate of adverse responses and produce only modest weight loss results.

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

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

About the study

The current study aimed to compare the on-treatment weight loss caused by 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 trials.

The researchers believe that because these medications are expensive and most health insurance companies will not cover them for obese or overweight people who do not have type 2 diabetes, adherence to both therapies may differ in the clinical context.

The trial included overweight and obese people who had recently began using semaglutide or tirzepatide, regardless of whether they had type 2 diabetes. The day of the first dose of semaglutide or tirzepatide was designated as the study index date. The study only included adult participants with available baseline weight measures and who had regular healthcare interactions.

Follow-ups to assess weight loss or adverse events continued until the administration censored the treatment, therapy was discontinued, treatment was altered, or the trial was terminated, whichever came first.

The studies were conducted using electronic health record data that included demographic information, diagnoses, pharmaceutical prescription information, vital measures, laboratory test results, and surgical operations. The study also included information on social health drivers and drug dispensing information.

Tirzepatide is sold under the brand name Mounjaro, which is manufactured by Eli Lilly, while semaglutide is sold under the brand name Ozempic, manufactured by Novo Nordisk. The dosage was based on the brand’s recommendation of 5.0 mg tirzepatide or 0.5 mg semaglutide. Both drugs were labeled for type 2 diabetes at the time of the trial.

The analysis also took into account the patient’s comorbidities and confounders. Comorbidities included insulin prescription or use and a hemoglobin A1c (HbA1c) level greater than 7.5% in the previous two years. The major outcome of interest was weight loss during treatment. Secondary outcomes included the study’s safety findings, which included gastrointestinal side events such pancreatitis, gastroparesis, cholelithiasis, and bowel obstruction.

Results

The results indicated that tirzepatide treatment in a clinical population resulted in considerably better weight loss in overweight or obese patients than semaglutide medication, regardless of the presence of type 2 diabetes.

The study discovered that overweight or obese people taking tirzepatide had a higher chance of losing equivalent to or more than 5%, 10%, and 15% of their body weight at three, six, and twelve months, respectively, compared to people on semaglutide.

Furthermore, the researchers discovered no significant difference in gastrointestinal side effects between semaglutide and tirzepatide treatment. These findings are consistent with the results of randomized control trials for both medications, as well as placebo-controlled trials, which found that tirzepatide treatment resulted in more significant weight loss than semaglutide treatment, regardless of type 2 diabetes status.

Conclusions

Overall, the study found that treating obesity or overweight with tirzepatide resulted in more weight loss than semaglutide medication, regardless of type 2 diabetes status. Furthermore, there were no significant differences in the risk of gastrointestinal ill effects between the two therapies.

For more information: Rodriguez, P. J., Brianna, Gratzl, S., Brar, R., Baker, C., Gluckman, T. J., & Stucky, N. L. (2024). Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Internal Medicine. DOI:10.1001/jamainternmed.2024.2525 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2821080