Eli Lilly, a dominant force in the obesity and type 2 diabetes market, has just beaten its biggest rival, with its newest weight loss and diabetes drug besting Novo Nordisk’s Ozempic (tirzepatide) in a head-to-head study.
In the Phase III TRANSCEND-T2D-2 trial (NCT06260722), Lilly’s investigational asset retatrutide, a triple glucagon, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist, more than doubled the weight loss of patients with type 2 diabetes. In the 9mg and 12mg cohorts of retatrutide, weight loss was reduced by 19.5% and 20.9%, respectively, while the 2mg Ozempic cohort saw a 9.4% reduction in weight loss. Weight loss was a key secondary endpoint in the study.
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The drug also showed a higher level of A1C reduction, with both retatrutide doses reporting a 2.2% reduction in A1C while Ozempic patients had an average reduction of 1.8%. A1C change was the trial’s primary endpoint.
Retatrutide also delivered greater improvements than Ozempic across certain cardiovascular risk factors, including non-HDL cholesterol, triglycerides and systolic blood pressure.
In the study, the most common adverse events (AEs) with retatrutide were mostly gastrointestinal in nature, as is well established with this modality, including diarrhoea, nausea, constipation, vomiting and dyspepsia.
The incidence of dysesthesia with retatrutide was 4.8% and 6.5% compared to 2.7% in Ozempic, while the incidence of urinary tract infections was 5.8% and 4.2% versus 5.8% in the same cohorts, respectively.
Treatment discontinuation rates due to adverse events were 4.8%, 7.9% and 2.7% with retatrutide 9mg and 12mg versus Ozempic, respectively.
Dr Kenneth Custer, executive VP 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 III 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.”
This data follows the TRIUMPH-1 study (NCT05929066), which compared retatrutide to placebo. In this study, after 80 weeks of treatment, patients randomised to the respective doses of retatrutide all experienced significant weight loss from baseline over placebo, with those given the highest dose of the drug losing 28.3% of their body weight compared with the 2.2% average in the placebo group. When this data was revealed in May 2026, senior GlobalData analyst Shehroz Mahmood said this result establishes retatrutide as “the highest-efficacy pharmacological weight loss agent to date in a large pivotal trial”.
Further data in July continued to establish the drug’s promise. In July, the fourth and fifth positive readouts came for the drug from TRIUMPH-2 (NCT05929079) and TRIUMPH-3 (NCT05882045).
In TRIUMPH-2, all three studied doses of retatrutide (4mg, 9mg, and 12mg) delivered substantial weight loss and improved glycaemic control at 80 weeks in adults with type 2 diabetes and obesity. Patients who received retatrutide lost an average of 29.8lbs (12.7%), 45.4lbs (19.1%), and 49.6lbs (20.8%) in the low, medium and high dose cohorts, respectively, alongside A1C reductions up to an average of 1.6%.
In TRIUMPH-3, both studied doses of retatrutide (9mg and 12mg) delivered substantial weight loss in adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes. Patients lost up to an average of 55.8lbs (22.6%) at 80 weeks.
Lilly and Novo continue to butt heads
Lilly and Novo continue to butt heads, even more so after Novo filed a lawsuit against its main competitor alleging that it produced misleading and false advertising campaigns.
The Danish drugmaker alleged that Lilly’s campaign was designed to mislead consumers about the “comparative efficacy” of weight loss and type 2 diabetes drugs in the companies’ respective portfolios. The company claims it did this through a “nationwide pattern of deceptive advertising”.
This case has now been closed, however, as the US courts backed Lilly, deeming that it could continue to advertise in the way it has been doing.
Beyond injectable options, Lilly and Novo are also fighting for dominance in the oral weight loss space, with both companies having marketed their first oral obesity drugs in 2026. Novo has gained a first-to-market advantage in the US, Europe and the UK, which are some of the key regions for these therapies.
GlobalData’s report, “GLP-1 Innovation Landscape 2026: Industry Insights,” reveals that the use of GLP-1RA drugs is rapidly expanding beyond treatments for diabetes and into mainstream weight management because they are effective at increasing satiety and reducing food intake, resulting in rapid weight loss.
Use among patients without diabetes but with overweight or obesity in the US rose 700% from 2019 to 2023, according to researchers from the University of Pennsylvania and Cedars-Sinai Medical Center.
While injectables remain the growth engine through 2031, the convenience and affordability of the GLP‑1RA pill format is expected to expand the user base, with pill market sales expected to rise from $3.2bn in 2025 to $34.3bn in 2031, according to GlobalData’s Pharmaceutical Intelligence Center.
GlobalData is the parent company of Clinical Trials Arena.
