Eli Lilly and Company has reported positive topline results from TRANSCEND-T2D-2, a Phase 3 clinical trial comparing its investigational drug retatrutide with injectable Ozempic (semaglutide) 2 mg in adults with type 2 diabetes. At 80 weeks, retatrutide met the primary and all key secondary endpoints, demonstrating greater reductions in glycated haemoglobin (A1C) and body weight than Ozempic.

Both doses of retatrutide, 9 mg and 12 mg, reduced A1C by an average of 2.2 percentage points at 80 weeks, compared with a 1.8-percentage-point reduction with Ozempic. Participants receiving the 9 mg dose lost an average of 44.3 pounds (19.5 percent of body weight), while those receiving 12 mg lost 47.4 pounds (20.9 percent). Participants treated with Ozempic lost an average of 20.9 pounds (9.4 percent).

Retatrutide also showed greater improvements than Ozempic in certain cardiovascular risk factors, including non-High-Density Lipoprotein (non-HDL) cholesterol, triglycerides and systolic blood pressure.

The most common adverse events reported in the trial included diarrhoea, nausea, constipation, vomiting and dyspepsia. Diarrhoea occurred in 28.3 percent of participants receiving retatrutide 9 mg, 32.7 percent receiving 12 mg and 26.4 percent receiving Ozempic. Nausea was reported in 21.2 percent, 23.8 percent and 21.3 percent of participants, respectively. Most reported events were mild to moderate and generally resolved during treatment.

Dysesthesia, an abnormal sensation such as tingling or burning, occurred in 4.8 percent of participants receiving retatrutide 9 mg, 6.5 percent receiving 12 mg and 2.7 percent receiving Ozempic. Urinary tract infections were reported in 5.8 percent, 4.2 percent and 5.8 percent of participants, respectively. Treatment discontinuation due to adverse events occurred in 4.8 percent of participants receiving retatrutide 9 mg, 7.9 percent receiving 12 mg and 2.7 percent receiving Ozempic.

Eli Lilly said detailed findings from TRANSCEND-T2D-2 will be presented at a future medical meeting and published in a peer-reviewed journal.

Retatrutide is an investigational, once-weekly triple hormone receptor agonist that activates receptors for Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon-like Peptide-1 (GLP-1) and glucagon. The drug is being evaluated in several Phase 3 clinical trials for obesity and overweight associated with weight-related medical conditions, type 2 diabetes, knee osteoarthritis pain, moderate-to-severe obstructive sleep apnoea, chronic low back pain, cardiovascular outcomes and metabolic dysfunction-associated steatotic liver disease. Retatrutide remains investigational and is not approved for human use.

TRANSCEND-T2D-2 (NCT06260722) is a randomised, open-label Phase 3 trial involving 1,298 adults with type 2 diabetes inadequately controlled with metformin, with or without a sodium-glucose cotransporter-2 (SGLT2) inhibitor. Participants were assigned in a 2:2:1 ratio to receive once-weekly retatrutide 9 mg, retatrutide 12 mg or Ozempic 2 mg. The primary objective was to establish the non-inferiority of retatrutide 12 mg to Ozempic 2 mg in A1C reduction at 80 weeks. The trial also includes an extension period in which approximately 650 participants will continue retatrutide treatment for another 24 weeks to assess longer-term efficacy and safety.

The broader TRANSCEND-T2D Phase 3 programme is evaluating the safety and efficacy of retatrutide in adults with type 2 diabetes through three global registrational trials. Initiated in 2024, the programme has enrolled more than 2,050 participants.