Glucagon-like peptide-1 receptor agonists (GLP-1RA) are very popular for weight loss, but results vary from person to person and from drug to drug. Venky Soundararajan and colleagues investigate the full spectrum of responses to tirzepatide (e.g., Mounjaro or Zepbound) and semaglutide (e.g., Ozempic, Wegovy, or Rybelsus) by analyzing deidentified electronic medical records of a matched cohort of 10,339 tirzepatide-treated patients and 10,339 semaglutide-treated patients.
In the real world, results range from minimal weight loss to more than 25% weight loss. Patients taking tirzepatide lost more weight than patients taking semaglutide (mean loss, 14.7% vs. 10.8% of body weight). There were almost twice as many “high responders” in the tirzepatide group as there were in the semaglutide group, defined as people who lost 15% or more of their body weight in one year. Tirzepatide patients had fewer gastrointestinal, headache, and fatigue adverse events than semaglutide patients. Women and white patients taking either drug achieved significant weight loss more often than men, blacks, and Hispanic patients, and were less than 5% likely to lose weight over a 1-year period. The authors say the reasons for these demographic patterns are unclear and need to be investigated.
sauce:
Reference magazines:
Venkatakrishnan, AJ, et al. (2026) Weight loss dynamics of tirzepatide and semaglutide; PNAS Nexus. DOI: 10.1093/pnasnexus/pgag171. https://academic.oup.com/pnasnexus/article/5/6/pgag171/8708114
