Eli Lilly’s Retatrutide Beats Ozempic in Head-to-Head Weight Loss and Diabetes Trial
Head-to-head trials show patients and physicians how a potential new medicine compares with treatments that are available and reimbursed today, according to Dr Kenneth Custer, executive VP and President of Lilly Cardiometabolic Health. Eli Lilly has reported that its experimental triple-agonist drug retatrutide outperformed Novo Nordisk’s Ozempic in a late-stage clinical trial involving adults with type 2 diabetes.
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Key Clinical Takeaways:
- In the Phase III TRANSCEND-T2D-2 trial, retatrutide achieved a 2.2% A1C reduction compared to 1.8% for Ozempic.
- Patients taking 9mg and 12mg doses of retatrutide lost 19.5% and 20.9% of their body weight, respectively, while the 2mg Ozempic cohort saw a 9.4% reduction.
- The trial evaluated nearly 1,300 adults whose diabetes was inadequately controlled with metformin, with or without an SGLT2 inhibitor.
Retatrutide Outperforms Ozempic in A1C Reduction
The open-label Phase III study, designated as NCT06260722, evaluated patients over an 80-week period. Participants received either 9mg or 12mg doses of retatrutide or a 2mg dose of Ozempic, which represents the highest approved dose of the competitor medication. At baseline, the participants’ A1C averaged 8.3%, with a range spanning from 7.0% to 10.5%. The trial’s primary endpoint measured changes in A1C levels, where both retatrutide cohorts demonstrated a 2.2% reduction, outperforming the 1.8% average reduction recorded in the Ozempic arm.
Weight loss served as a key secondary endpoint in the trial. Participants receiving the 9mg dose of retatrutide lost an average of 44.3 pounds (19.5%), while those on the 12mg dose lost an average of 47.4 pounds (20.9%). In comparison, patients in the Ozempic cohort experienced an average weight reduction of 20.9 pounds, or 9.4% of their baseline body weight. Beyond glycaemic control and weight reduction, retatrutide delivered greater improvements across specific cardiovascular risk factors, including non-HDL cholesterol, triglycerides, and systolic blood pressure.
Retatrutide Causes More Diarrhea than Ozempic
The safety and tolerability data from the study indicate that retatrutide’s efficacy is accompanied by distinct adverse events, primarily gastrointestinal in nature. Common side effects reported across the trial cohorts included diarrhea, nausea, constipation, vomiting, and dyspepsia. The incidence of diarrhea affected up to 32.7% of patients on retatrutide compared to 26.4% on Ozempic. Conversely, the rate of constipation was higher on Ozempic at 19.8%, compared to up to 14.2% for patients receiving retatrutide.
Additional adverse events included dysesthesia, which was observed in 4.8% and 6.5% of the 9mg and 12mg retatrutide cohorts, respectively, compared to 2.7% in the Ozempic group. Urinary tract infections occurred in 5.8% and 4.2% of the retatrutide cohorts, versus 5.8% of patients taking Ozempic. Treatment discontinuation rates due to adverse events reached 4.8% in the 9mg retatrutide group and 7.9% in the 12mg retatrutide group, compared to 2.7% for patients in the Ozempic arm.
The latest trial data build on a series of readouts for retatrutide, an investigational molecule that activates three distinct hormone receptors: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon. In March, Lilly released data from a placebo-controlled trial evaluating the drug in type 2 diabetes. The TRIUMPH clinical program, which includes the TRIUMPH-1, TRIUMPH-2, and TRIUMPH-3 studies, has evaluated the asset across populations with obesity, type 2 diabetes, and established cardiovascular disease.
When May 2026 data from the TRIUMPH-1 trial were revealed, senior GlobalData analyst Shehroz Mahmood stated that the results established retatrutide as the highest-efficacy pharmacological weight loss agent to date in a large trial. Beyond injectable formulations, Eli Lilly and Novo Nordisk continue to compete in the oral weight loss drug market, where Novo has secured early first-to-market advantages in the United States, Europe, and the United Kingdom. Market analysts project that global sales within the oral GLP-1 receptor agonist category will rise from $3.2bn in 2025 to $34.3bn by 2031.
Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.