Semaglutide primarily activates the GLP-1 receptor. Tirzepatide activates GLP-1 and GIP receptors, while retatrutide is an investigational triple agonist targeting GLP-1, GIP, and glucagon receptors. Because they work somewhat differently, their weight-loss results, side effects, and suitability can differ from person to person. Retatrutide should not be treated as an approved alternative to the other two because it remains investigational.

Both can produce substantial weight loss, but clinical trials have generally shown greater average weight loss with tirzepatide than with semaglutide in comparable obesity-treatment settings. Individual results vary considerably, so the “best” medication depends on medical history, side effects, treatment goals, and other factors.

“Stronger” isn't a precise medical term. Tirzepatide acts on two hormone receptors, GLP-1 and GIP, whereas semaglutide primarily acts on GLP-1. Tirzepatide has demonstrated greater average weight reduction in head-to-head research, but that does not mean it is automatically better or safer for every person.

Weight loss varies by dose, duration of treatment, starting weight, lifestyle, and individual response. Clinical trials have demonstrated substantial average weight reductions with tirzepatide, but those trial averages should not be interpreted as a guarantee for an individual patient.

Semaglutide can produce significant weight loss when used as indicated along with dietary and physical-activity changes. The amount varies from person to person. The FDA-approved Wegovy labeling describes its use for reducing excess body weight and maintaining weight reduction long term in eligible patients.

Early and later clinical trials have shown very promising weight-loss results, but retatrutide is still an investigational medication. Its clinical-trial results should not be presented as an expected result for someone taking an unapproved product. Lilly specifically warns against taking products claiming to be retatrutide outside a Lilly-sponsored clinical trial.