1858-LB: A Novel GLP-1 Analog, GZR18, Induced an 18.6% Weight Reduction in Subjects with Obesity in a Phase Ib/IIa Trial

It remains unclear whether the superior efficacy of multi-target incretin analogs versus single-target incretins in obesity treatment. This randomized, double-blind, placebo-controlled, dose-escalation phase Ib/IIa study aimed to assess the efficacy and safety of a GLP-1 analog, GZR18, in Chinese adults with obesity. The study investigated the weight loss potential of GZR18 and evaluated the feasibility of administrating GZR18 at different frequencies. Thirty-six participants with obesity were randomized 3:1 to receive 30 mg of GZR18 or a placebo for 35 weeks, including a 31-week dose-escalation period. Upon dose escalation to 9 mg/week, subjects were divided into dosing sub-cohorts of QW or Q2W. Endpoints were body weight change and AEs incidence. The average weight loss of GZR18 adjusted by placebo was 18.6% in QW group and 13.5% in Q2W group, with no IP-related serious AEs. Gastrointestinal AEs were reported most frequently, mainly in early dose-escalation period. GZR18 reduced body weight robustly and improved metabolic profiles in study participants. Its weight-loss effects surpassed those of Semaglutide (2.4 mg) and Tirzepatide (15 mg) in recent phase 3 trials involving similar Chinese populations (-9.8% and -17.5%, respectively). These findings warrant further investigation into GZR18's potential to offer superior weight management efficacy over multi-target incretin analogs.