Wegovy
vs. Zepbound vs. Retatrutide
These three medications all target pathways involved in appetite and metabolism, but they do not work in exactly the same way.
| Ozempic / Wegovy (semaglutide) |
Zepbound (tirzepatide) |
Retatrutide | |
|---|---|---|---|
| Targets | GLP-1 | GLP-1 + GIP | GLP-1 + GIP + glucagon |
| Type | Single agonist | Dual agonist | Triple agonist |
| Basic idea | Influences appetite, gastric emptying and glucose regulation | Adds GIP receptor activity to GLP-1 activity | Adds glucagon receptor activity to GLP-1 and GIP |
| Injection | Once weekly | Once weekly | Once weekly in clinical trials |
| FDA status | Ozempic: approved for type 2 diabetes; Wegovy: approved for chronic weight management | Approved for chronic weight management | Investigational; not FDA approved |
| My journey | Where I started | Where I lost most of my weight | Where I am now |
So What Makes Retatrutide Different?
The interesting addition is the glucagon receptor.
Retatrutide activates three hormone receptors—GLP-1, GIP and glucagon—while semaglutide targets GLP-1 and tirzepatide targets GLP-1 and GIP. Researchers are studying whether adding glucagon-receptor activity can influence not only appetite and glucose regulation, but also energy expenditure and the way the body uses stored energy.
The clinical-trial results have attracted considerable attention. In the Phase 2 obesity trial, participants receiving 12 mg of Retatrutide lost an average of 24.2% of their starting body weight after 48 weeks.
In Lilly's Phase 3 TRIUMPH-1 trial, participants receiving 12 mg lost an average of 28.3% of their body weight after 80 weeks.
Those numbers are averages from controlled clinical trials and do not predict what will happen to any individual person.
As of September 2026, Retatrutide remains investigational and is not FDA approved.
What did the Retatrutide studies actually show?
In the Phase 2 obesity trial, 338 adults were assigned to different doses of Retatrutide or placebo and treated for 48 weeks. Weight loss increased with dose, and participants receiving 12 mg lost an average of 24.2% of their starting body weight, compared with 2.1% with placebo. The most common side effects were gastrointestinal, and they were generally more frequent at higher doses.
More recently, the Phase 3 TRIUMPH-1 trial reported that participants receiving 12 mg of Retatrutide lost an average of 28.3% of their body weight after 80 weeks, while the 4 mg group lost an average of 19.0%. Retatrutide remains investigational and is not yet FDA approved.
These results are impressive, but they are averages from large groups of people under controlled study conditions, so they cannot predict how any one individual will respond.