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Cosmos Study

Tirzepatide and Injectable Semaglutide Correlated with Greatest Weight Loss Among GLP-1 Medications

March 14, 2024
Dual-Team Study
Team A:Kersten Bartelt, RNJoe Deckert, PhD
Team B:Dave Little, MDBrendan Joyce

Key Findings

  • After one year of treatment, patients on any dosage of tirzepatide or injectable semaglutide experienced greater median weight loss than those on any dosage of liraglutide, dulaglutide, or oral semaglutide.  
  • Patients on tirzepatide lost the greatest percentage of weight compared to all other GLP-1 medications studied. Patients on 10 mg and 15 mg of tirzepatide experienced a median weight loss of 13.2% and 15%, respectively. 

In a previous study, we found that patients on injectable semaglutide at the recommended weight loss dosage (2.4mg) for 60 weeks achieved an 8-11% reduction of their starting weight.1 Two other glucagon-like peptide-1 receptor agonist (GLP-1) medications, tirzepatide and liraglutide, have also been approved for weight loss by the FDA.2,3  

To better understand how different GLP-1 medications, routes, and dosages might influence weight change, we studied 413,557 patients who were prescribed tirzepatide, liraglutide, dulaglutide, or injectable or oral semaglutide for a minimum of 180 days. We stratified patients by the peak dosage of the medication prescribed within the year of GLP-1 treatment to determine how dosage might influence the amount of weight loss experienced. We found that higher dosages of all GLP-1 medications studied were associated with greater median weight loss a year after starting the medication, as seen in Figure 1. Patients on tirzepatide experienced greater weight loss than those on liraglutide, dulaglutide, oral semaglutide, and all but the highest dose of injectable semaglutide. Patients on injectable semaglutide achieved greater median weight loss than patients prescribed oral semaglutide. 

Figure 1
Median Weight Loss After One Year by Peak Dosage
Median Weight Loss After One Year by Peak Dosage
Figure 1. Patients’ median weight loss by the peak dosage of the GLP-1 receptor agonist prescribed within the year of starting it.

The study population includes both diabetic and non-diabetic patients. Some of the medications and dosages studied, including oral semaglutide, dulaglutide, the 0.6 mg dosage of liraglutide, and the 1 mg and 2 mg dosages of injectable semaglutide, have not been approved by the FDA for the treatment of obesity.1,2,3 As such, the patients prescribed these medications are much more likely to have been prescribed these medications for diabetes management compared to the patients prescribed the medications and dosages approved for weight loss. This may explain some of the differences observed in the median percentage of weight loss seen across the different medications and dosages. 

These data come from Cosmos, a collaboration of Epic health systems representing more than 238 million patient records from 1,345 hospitals and more than 28,975 clinics from all 50 states and Lebanon. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Kayla Monnette.

  1. Little D, Deckert J, Bartelt K, Ganesh M, Stamp T. Weight Change with Semaglutide. Epic Research. https://epicresearch.org/articles/diabetes-drug-helps-with-weight-loss-in-both-diabetics-and-non-diabetics. Accessed March 6, 2024. 
  2. FDA Approves New Medication for Chronic Weight Management. U.S. Food and Drug Administration. Published November 8, 2023.  https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management. Accessed March 6, 2024. 
  3. FDA Approves Weight Management Drug for Patients Aged 12 and Older. U.S Food and Drug Administration. Published December 4, 2020. FDA approves weight management drug for patients aged 12 and older | FDA. Accessed March 6, 2024.