Abstract
Abstract
Safiglipron is an oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist administered without fasting or dietary restrictions. We evaluated its efficacy and safety versus dapagliflozin in OUTSTAND-2, a phase 3, multicenter, randomized, double-blind, double-dummy, active-comparator-controlled trial conducted at 98 sites in China. We randomized 810 adults (mean hemoglobin A1C (HbA1c) 8.60%, median diabetes duration 5.0 years, 35.7% women) to safiglipron 30 mg (
n
= 202), safiglipron 60 mg (
n
= 203), safiglipron 90 mg (
n
= 203) or dapagliflozin 10 mg (
n
= 202) for 32 weeks, followed by a 20-week active-treatment extension. For the primary endpoint, treatment differences versus dapagliflozin in change from baseline in HbA1c at week 32 under the primary non-inferiority estimand were −0.30% (95% confidence interval (CI): −0.51 to −0.09), −0.22% (−0.44 to −0.01) and −0.40% (−0.62 to −0.19) for safiglipron 30 mg, 60 mg and 90 mg, respectively, establishing non-inferiority for all three doses (all
P
P
= 0.0067), whereas 60 mg did not (
P
= 0.0789), after which fixed-sequence testing stopped. HbA1c target attainment rates with safiglipron versus dapagliflozin were 54.9−63.5% versus 36.5% for HbA1c NCT06589765
.