Eli Lilly’s experimental drug retatrutide has outperformed Ozempic’s highest approved dose for type 2 diabetes in a head-to-head Phase 3 trial, delivering more than double the weight loss and greater reductions in blood sugar levels over 80 weeks.

 

The results, announced by Lilly on October 28, 2026, mark a potentially significant development in the treatment of type 2 diabetes and obesity. However, retatrutide remains an investigational drug and has not been approved by the US Food and Drug Administration (FDA) or any other regulatory authority worldwide.

 

In the TRANSCEND-T2D-2 trial, participants taking retatrutide lost an average of 44.3 pounds (19.5%) on the 9 mg dose and 47.4 pounds (20.9%) on the 12 mg dose. Those receiving injectable Ozempic 2 mg lost an average of 20.9 pounds (9.4%) over the same period.

 

The blood sugar results also favoured retatrutide. Both doses reduced average glycated haemoglobin (A1C), a key measure of blood sugar control, by 2.2 percentage points, compared with a 1.8-point reduction with Ozempic.

 

The trial enrolled 1,298 adults with type 2 diabetes whose blood sugar levels were inadequately controlled with metformin, with or without an SGLT2 inhibitor.

 

The findings represent the first Phase 3 head-to-head comparison of retatrutide with another incretin-based medicine, according to Lilly. The company said the drug met its primary and all key secondary endpoints.

 

Kenneth Custer, Executive Vice President and President of Lilly Cardiometabolic Health, said: "Head-to-head trials show patients and physicians how a potential new medicine compares with treatments that are available and reimbursed today. In TRANSCEND-T2D-2, the first Phase 3 trial comparing retatrutide with another incretin medicine, retatrutide delivered greater A1C reduction and more than double the weight loss of the highest approved dose of Ozempic for type 2 diabetes. 

 

"Based on these results and those from across our Phase 3 program, we believe retatrutide, if approved, could shift the treatment paradigm for people living with type 2 diabetes, obesity and related cardiometabolic conditions."

 

Beyond weight loss and blood sugar control, retatrutide also produced greater improvements in certain cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure, compared with Ozempic, the company said.

 

Detailed trial results are expected to be presented at a future medical meeting and published in a peer-reviewed journal.

 

The stronger results came with gastrointestinal side effects, which were among the most common adverse events reported in the trial.

 

Diarrhoea occurred in 28.3% of participants receiving retatrutide 9 mg and 32.7% of those on 12 mg, compared with 26.4% among Ozempic users. Nausea was reported by 21.2% and 23.8% of participants taking the two retatrutide doses, respectively, versus 21.3% with Ozempic.

 

Vomiting was reported in 10.2% of the 9 mg group and 15% of the 12 mg group, compared with 13.2% in the Ozempic group. Constipation was less common with retatrutide than with Ozempic.

 

Treatment discontinuation because of adverse events was higher among retatrutide users. The rates were 4.8% for the 9 mg dose and 7.9% for the 12 mg dose, compared with 2.7% for Ozempic.

 

Lilly said most of the reported adverse events were mild to moderate and typically resolved during treatment.

 

Retatrutide is a once-weekly investigational medicine designed to activate three hormone receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon.

 

This triple-receptor mechanism distinguishes it from medicines that target fewer hormonal pathways. Lilly is studying retatrutide across multiple Phase 3 trials for obesity, type 2 diabetes and other conditions linked to metabolic health, including obstructive sleep apnoea, knee osteoarthritis pain and chronic low back pain.

 

The company has also launched TRIUMPH-5, an ongoing Phase 3 trial comparing retatrutide directly with tirzepatide in adults with obesity, with or without type 2 diabetes.

 

Lilly said retatrutide has now delivered positive efficacy results in six Phase 3 trials, strengthening its case as a potential treatment for cardiometabolic disease.

 

But the latest findings do not yet establish how the drug will perform in routine clinical practice, and its safety and efficacy must be assessed through the regulatory review process.

 

For now, retatrutide remains unavailable as an approved prescription medicine. Lilly has warned that anyone claiming to sell the investigational drug directly to consumers is acting unlawfully.

 

If approved, retatrutide could intensify competition in the fast-growing market for diabetes and obesity treatments. For patients, the key questions will extend beyond the scale of weight loss to long-term safety, sustained benefits, tolerability, affordability and access.