Oral safiglipron lowers HbA1c in phase 3 trial of early type 2 diabetes

OUTSTAND-1 evaluated safiglipron, an oral small-molecule GLP-1 receptor agonist taken without fasting or dietary restrictions, in 284 adults with type 2 diabetes managed with diet and exercise alone. The randomized, double-blind phase 3 trial at 46 Chinese sites compared once-daily doses of 30, 60 or 90 mg with placebo for 32 weeks, followed by a 20-week active-treatment extension. Mean baseline HbA1c was 7.95%, and median diabetes duration was 1.6 years.

For the primary endpoint, placebo-adjusted HbA1c reductions at week 32 were 1.22, 1.20 and 1.45 percentage points with 30, 60 and 90 mg, respectively (all P < 0.0001). HbA1c below 7.0% was achieved by 71.4–77.8% of safiglipron recipients versus 25.0% receiving placebo. Corresponding placebo-adjusted body weight differences were −0.65%, −2.23% and −3.56%.

Gastrointestinal adverse events were most common and generally mild or moderate. Adverse events caused treatment discontinuation in 1.4%, 2.9% and 6.9% of participants receiving the ascending safiglipron doses, compared with none receiving placebo.

The findings support glycemic efficacy in early type 2 diabetes, with modest weight effects. Interpretation is limited by the placebo comparator, the population treated only with lifestyle measures and enrollment exclusively in China. The reported surrogate outcomes and 32-week controlled comparison do not establish long-term cardiovascular benefit or comparative effectiveness against established therapies.