Supaglutide (Supa) is a weekly dosing GLP-1 analog. We conducted a randomized, double-blind, placebo-controlled, multiple dose-escalation study to investigate the safety, PK/PD and efficacy of Supa in patients with T2D. 40 subjects were randomized in a 4:1 ratio to receive Supa (sc., 1, 2, 3 and 4mg) or placebo. We performed intensive PK blood sampling for two weeks after the first dose, followed by weekly repeated dosing for 4 consecutive weeks. The 4mg group received an adaptive dose of 1mg to reduce gastrointestinal reactions. The PK results revealed that the T1/2 of Supa was ∼207 h with median Tmax of 60∼84 h. The PD results showed that after 7 weeks of therapy, Supa significantly reduced fasting blood glucose, and HbA1c decreased by 1.3%. Supa increased fasting insulin/C-peptide while decreasing body weight. OGTT results showed significantly reduced glucose excursion, and the glucose-stimulated insulin secretion assay demonstrated significantly increased insulin secretion, suggesting improved glucose tolerance and enhanced β-cell function. AEs identified during the study were mainly mild to moderate gastrointestinal symptoms. None of the subjects developed anti-drug antibodies. Safety assessments including AEs, vital signs, ECGs and laboratory parameters, revealed that Supa was safe and well-tolerated. These data suggest Supa is a novel alternative therapy for T2D and metabolic disorders. Disclosure Y. Zhou: None. X. Jiang: None. Y. Lou: None. A. Ma: None. J. Li: None. Y. Zhao: None. G. J. Prud'homme: None. Q. Wang: None.