Oral small-molecule GLP-1 agonist safiglipron shows strong glycemic control in early type 2 diabetes trial (OUTSTAND-1)

Safiglipron (Jiangsu Hengrui Pharmaceuticals), an oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist , produced substantial reductions in HbA1c in adults with early type 2 diabetes, according to results of the phase 3 OUTSTAND-1 trial published in Nature Medicine. Unlike some other agents in its class, safiglipron is administered once daily without fasting or dietary restrictions.

OUTSTAND-1 was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 46 hospitals in China. Investigators randomized 284 adults with type 2 diabetes managed by diet and exercise alone (mean baseline HbA1c, 7.95%; median disease duration, 1.6 years; 33.1% women) to once-daily safiglipron 30mg, 60mg, or 90mg, or placebo, for a 32-week core period followed by a 20-week active-treatment extension.

For the primary endpoint, placebo-adjusted HbA1c reductions from baseline to week 32 were −1.22% (95% CI, −1.53 to −0.91) with 30 mg, −1.20% (95% CI, −1.52 to −0.89) with 60 mg, and −1.45% (95% CI, −1.75 to −1.14) with 90 mg (all P<0.0001). HbA1c fell below 7.0% in 71.4% to 77.8% of safiglipron-treated patients versus 25.0% on placebo. The authors noted that this magnitude of glycemic lowering "places safiglipron within the range reported for oral GLP-1 receptor agonist monotherapy" in prior trials of oral semaglutide and orforglipron, while cautioning that such cross-trial comparisons "provide clinical context rather than evidence of comparative efficacy."

Body weight reductions were dose-dependent and more modest, reaching statistical significance only at 60 mg (−2.23% versus placebo; P=0.0028) and 90 mg (−3.56%; P<0.0001), not at 30 mg (P=0.21). Gastrointestinal adverse events — mostly mild or moderate — were the most common side effects and increased with dose (44.3%–73.6% versus 15.3% with placebo); treatment discontinuations due to adverse events occurred in 1.4% to 6.9% of safiglipron-treated patients versus none on placebo. No severe hypoglycemia or deaths occurred. The authors identified key limitations: all participants were Chinese, limiting generalizability to other populations, and the trial was powered for glycemic efficacy rather than for rare adverse events or cardiovascular and renal outcomes.

Source: Yu M, Peng L, Jiang C, et al. Oral small-molecule GLP-1 receptor agonist safiglipron in early type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Nat Med. Published online September 29, 2026. doi:10.1038/s41591-026-04651-9