Tirzepatide outperforms semaglutide for real-world weight loss

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become massively popular for weight loss, but results vary from person to person and drug to drug. Venky Soundararajan and colleagues explore the full range of responses to tirzepatide (e.g., Mounjaro or Zepbound) and semaglutide (e.g.,Ozempic, Wegovy, or Rybelsus) by analyzing de-identified electronic health records for matched cohorts of 10,339 tirzepatide-treated and 10,339 semaglutide-treated patients.

In the real world, outcomes ranged from minimal weight loss to more than 25% reduction in body weight. Patients taking tirzepatide lost more weight than those taking semaglutide (mean reduction, 14.7% vs. 10.8% of body weight). The tirzepatide group had nearly twice as many "high responders," defined as people who lost more than 15% of their body weight in a year, as the semaglutide group. Tirzepatide patients also had fewer gastrointestinal, headache, and fatigue adverse events than semaglutide patients. Female and white patients on either drug more frequently achieved significant weight loss than male, black, and Hispanic patients, who were more likely to lose less than 5% of their body weight in a year. According to the authors, the reasons for these demographic patterns are unknown and should be investigated.