Lilly’s Retatrutide Shows Greater A1C Reduction in Type 2 Diabetes Trial

Eli Lilly’s experimental obesity and diabetes drug retatrutide has delivered stronger blood sugar control and more than twice the weight loss compared with Novo Nordisk’s Ozempic in a Phase 3 clinical trial.

The results come from TRANSCEND-T2D-2, a head-to-head study involving 1,298 adults with type 2 diabetes. The trial compared two doses of retatrutide, 9 mg and 12 mg, with Ozempic 2 mg, the highest approved dose of the drug for type 2 diabetes.

After 80 weeks of treatment, participants receiving both doses of retatrutide recorded an average reduction of 2.2 percentage points in HbA1c, a measure of average blood sugar levels over time. In comparison, those receiving Ozempic recorded an average reduction of 1.8 percentage points.

The difference was also clear in weight loss. Participants taking the 9 mg dose of retatrutide lost an average of 44.3 pounds (19.5%) of their body weight, while those receiving the 12 mg dose lost 47.4 pounds (20.9%). Participants taking Ozempic lost an average of 20.9 pounds (9.4%).

Retatrutide also showed greater improvements in certain cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure.

Lilly reported that the study met its primary endpoint and all key secondary endpoints. This is the first Phase 3 trial to compare retatrutide directly with another incretin-based medicine.

The safety results showed that gastrointestinal problems were among the most common side effects. These included diarrhoea, nausea, constipation, vomiting and indigestion. Most events were mild to moderate and generally improved during treatment.

Treatment discontinuation due to side effects was reported in 4.8% of participants receiving retatrutide 9 mg and 7.9% of those receiving 12 mg. The rate was 2.7% among participants taking Ozempic.

Retatrutide is a once-weekly investigational medicine that works on three hormone receptors: GIP, GLP-1 and glucagon. By targeting all three pathways, the drug is designed to improve blood sugar control, reduce appetite and support weight loss.

Lilly said the latest findings add to the growing evidence from its Phase 3 retatrutide programme. TRANSCEND-T2D-2 is the sixth Phase 3 trial in which the medicine has demonstrated encouraging results.

The company is also studying retatrutide in other conditions, including obesity, knee osteoarthritis pain, obstructive sleep apnoea and metabolic dysfunction-associated steatotic liver disease.

Lilly plans to present the detailed findings from TRANSCEND-T2D-2 at a future medical meeting and publish the results in a peer-reviewed journal. The company is also conducting another Phase 3 study, TRIUMPH-5, comparing retatrutide with tirzepatide in people with obesity, with or without type 2 diabetes.

Despite the encouraging results, retatrutide remains an investigational medicine and has not been approved by the US Food and Drug Administration (FDA) or any other regulatory authority. Further clinical data and regulatory review will be needed before it can become available as an approved treatment.