Eli Lilly said Wednesday that its experimental drug retatrutide produced substantially greater weight loss and a larger reduction in average blood sugar than Ozempic in a Phase 3 trial involving adults with Type 2 diabetes. The results come from a direct comparison with Novo Nordisk’s diabetes treatment, but they do not represent an FDA approval for retatrutide.
The 80-week study enrolled 1,298 adults whose Type 2 diabetes was not adequately controlled with metformin, either alone or alongside another medicine. Participants received either a 9-milligram or 12-milligram dose of retatrutide, or a 2-milligram dose of Ozempic. Lilly described the results as showing that retatrutide reduced body weight by more than twice as much as Ozempic in the trial.
Weight and blood-sugar results
Participants weighed an average of about 226 pounds at the beginning of the study. After 80 weeks, average weight loss reached 44.3 pounds among people taking the 9-milligram retatrutide dose and 47.4 pounds among those taking 12 milligrams. The Ozempic group lost an average of 20.9 pounds.
| Treatment | Average weight loss | Average A1C reduction |
|---|---|---|
| Retatrutide, 9 milligrams | 44.3 pounds | 2.2 percentage points |
| Retatrutide, 12 milligrams | 47.4 pounds | 2.2 percentage points |
| Ozempic, 2 milligrams | 20.9 pounds | 1.8 percentage points |
A1C measures average blood sugar over time. Lilly said the average A1C reduction was 2.2 percentage points with retatrutide, compared with 1.8 percentage points for Ozempic. The company also reported greater improvements in some cardiovascular risk factors, including cholesterol and blood pressure.
The study did not determine whether retatrutide lowers the risk of heart attacks or strokes. That distinction is significant because evidence for a drug’s effects on those outcomes is separate from measurements of weight, blood sugar, cholesterol or blood pressure. The trial therefore provides comparative results for the reported measures, not proof of a reduction in cardiovascular events.
Tolerability remains an issue
Stomach-related problems were the most common side effects reported among retatrutide users. Participants receiving retatrutide were more likely to discontinue treatment because of side effects than those receiving Ozempic. Lilly reported that 7.9% of participants on the 12-milligram retatrutide dose stopped treatment for that reason, compared with 2.7% of those taking Ozempic.
“Ozempic should not be evaluated solely by weight loss, as its broad, extensive clinical evidence has also proven protection for the heart, kidneys and liver in people living with Type 2 diabetes. It also has an established safety and tolerability profile and has been used by more than 28 million people worldwide.” — Liz Skrbkova, Novo Nordisk spokesperson
Novo Nordisk spokesperson Liz Skrbkova pointed to Ozempic’s broader clinical evidence and established use in responding to Lilly’s comparison. Ozempic’s 2-milligram dose was the highest approved dose for people with Type 2 diabetes in the trial described by Lilly.
Next regulatory step
Lilly already markets Zepbound for weight loss and Mounjaro for Type 2 diabetes. The company has said it expects to seek Food and Drug Administration approval for retatrutide before the end of March 2027. Until regulators review the application and issue a decision, retatrutide remains an investigational treatment.
- The Phase 3 trial included 1,298 adults with inadequately controlled Type 2 diabetes.
- Average weight loss was 44.3 pounds or 47.4 pounds with retatrutide, versus 20.9 pounds with Ozempic.
- Discontinuation because of side effects was higher with the 12-milligram retatrutide dose than with Ozempic.
