Eli Lilly’s oral glucagon-like peptide-1 receptor agonist (GLP-1RA) has shown success again in two more Phase III trials in patients with type 2 diabetes.
In the ACHIEVE-2 (NCT06192108) orforglipron showed superiority over dapagliflozin, an SGLT-2 inhibitor, meeting the primary and all secondary endpoints in all three doses (3mg, 12mg and 16mg), with a 1.3%, 1.7% and 1.7% reduction in A1C in the three arms, respectively. This is compared to a 0.8% reduction in patients treated with dapagliflozin – a drug marketed as Farxiga in the US by AstraZeneca for type 2 diabetes treatment
Meanwhile, the ACHIEVE-5 (NCT06109311), comparing the study drug to placebo, also met all its endpoints in the three doses, with a 1.5%, 2.1% and 1.9% reduction in A1C levels in the low, medium and high dose cohorts, respectively. The placebo cohort saw a 0.8% reduction in A1C.
Both trials also reported improved weight loss as well as improvements in multiple cardiovascular risk factors, and the safety and tolerability profile was consistent with previous studies.
ACHIEVE-2 enrolled patients with type 2 diabetes who were inadequately controlled on metformin while ACHIEVE-5 included type 2 diabetes patients who had inadequate glycaemic control with titrated insulin glargine, with or without metformin and/or SGLT-2 inhibitors.
Dr Jeff Emmick, senior vice president of product development at Lilly Cardiometabolic Health, said: "Orforglipron has now demonstrated superiority over two active comparators in clinical trials for type 2 diabetes. In ACHIEVE-2, orforglipron outperformed dapagliflozin, a commonly used SGLT-2 therapy, and in ACHIEVE-3, showed greater efficacy than oral semaglutide. The findings from ACHIEVE-5 add to this momentum, showing significant A1C reduction and weight loss when used in combination with titrated basal insulin.”
Emmick added that the combined data from the three trials, along with others in the ACHIEVE programme, support orforglipron's potential to become a standard of care (SoC) in type 2 diabetes.
This comes after the drug also showed promise in a weight loss study, the Phase III ATTAIN-1 trial, where the high dose cohort (36mg) saw a 12.4% reduction in weight after 72 weeks of dosing. The ATTAIN-2 trial, which evaluated the drug in patients with obesity and type 2 diabetes, also met all its endpoints.
Lilly is continuing with its goal of submitting for approval of orforglipron in obesity by the end of 2025, and in type 2 diabetes in 2026. GlobalData predicts a global annual sales and consensus forecast of $11bn in 2031.
GlobalData is the parent company of Clinical Trials Arena.
Lilly’s major competitor, Novo Nordisk, is further ahead in the process, having cemented the status of its oral GLP-1RA Rybelsus (semaglutide) in the type 2 diabetes market since its September 2019 US approval. It has already completed its submission for the approval of the drug in obesity.
