Oral Orforglipron demonstrates non-inferiority to dapagliflozin in reducing HbA1c for type 2 diabetes

Type 2 diabetes (T2D) is a progressive metabolic disorder often requiring combination therapy to achieve optimal glycaemic control. Current treatments, while effective, may not always provide sustained control or offer convenient oral administration for all mechanisms. This study investigates orforglipron, an oral, non-peptide GLP-1 receptor agonist, as a potential alternative or adjunct, comparing its efficacy and safety against dapagliflozin, an oral SGLT2 inhibitor, in patients with T2D whose HbA1c levels remain elevated despite metformin therapy.

This 40-week, phase 3, multicentre, open-label, randomized study enrolled 962 adults with type 2 diabetes on metformin (≥1500 mg/day) and HbA1c between 7.0% and 10.5%. Participants were randomized 1:1:1:1 to receive once-daily oral orforglipron at 3 mg, 12 mg, or 36 mg, or dapagliflozin 10 mg. The primary endpoint was the change from baseline in HbA1c at week 40, assessed for non-inferiority of orforglipron versus dapagliflozin with a 0.3% margin. Safety was evaluated in all randomized participants receiving at least one dose of the study drug.

A total of 962 participants were randomized across four arms: orforglipron 3 mg (n=240), 12 mg (n=241), 36 mg (n=241), and dapagliflozin 10 mg (n=240). The baseline population had a mean age of 56.1 years, mean HbA1c of 8.14%, and mean BMI of 32.6 kg/m2. At week 40, for the treatment regimen estimand, all tested doses of orforglipron demonstrated non-inferiority to dapagliflozin in reducing HbA1c. Specific numerical reductions in HbA1c and detailed statistical comparisons for each dose group were not fully provided in the truncated abstract.

All orforglipron doses were non-inferior to dapagliflozin in reducing HbA1c at week 40 in adults with type 2 diabetes. The abstract indicates that the study is registered as NCT06192108 and has been completed.