Oral small-molecule GLP-1 receptor agonist safiglipron in early type 2 diabetes: a randomized, double-blind, placebo-controlled trial.

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 in OUTSTAND-1, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial at 46 sites in China. We randomized 284 adults with type 2 diabetes managed with diet and exercise alone (mean baseline HbA1c 7.95%, median diabetes duration 1.6 years, 33.1% women) to once-daily safiglipron 30 mg (n = 70), 60 mg (n = 70), 90 mg (n = 72) or placebo (n = 72) for 32 weeks, followed by a 20-week active-treatment extension. For the primary endpoint, placebo-adjusted treatment differences in HbA1c change from baseline to week 32 were -1.22% (95% CI, -1.53 to -0.91), -1.20% (95% CI, -1.52 to -0.89) and -1.45% (95% CI, -1.75 to -1.14) for 30 mg, 60 mg and 90 mg, respectively (all P < 0.0001; treatment policy estimand). Secondary outcomes showed HbA1c < 7.0% in 71.4-77.8% versus 25.0%, HbA1c ≤ 6.5% in 58.6-68.1% versus 16.7% and placebo-adjusted fasting plasma glucose differences of -1.58, -1.68 and -2.08 mmol l