Efficacy and Safety of Bilpatide, a Bi-weekly GIP/GLP-1 Receptor Agonist, in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

Abstract Bilpatide is a novel bi-weekly dual receptor agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) developed for the treatment of obesity and type 2 diabetes (T2D). Here we report the SHINING-1 randomized, double-blind, placebo-controlled phase 2 trial assessing the efficacy and safety of bilpatide compared with placebo in Chinese participants with T2D uncontrolled by lifestyle intervention or metformin combination therapy. In this study, 233 participants were randomized to receive bilpatide 3 mg, 6 mg, 9 mg, 12 mg or 15 mg, or placebo for 24 weeks. All bilpatide doses produced significant, dose-dependent reductions in glycated haemoglobin A1c (HbA1c) from baseline to week 24 versus placebo, with least-squares mean changes of -1.66% for 3 mg, -2.04% for 6 mg, -2.14% for 9 mg, -2.34% for 12 mg, and − 2.76% for 15 mg, compared with − 0.25% for placebo(all P < 0.001). More participants receiving bilpatide achieved HbA1c < 7.0% and < 6.5%, and body-weight loss ≥ 5% and ≥ 10%, than those receiving placebo. The most common treatment-emergent adverse events were gastrointestinal, predominantly mild or moderate in severity. No severe hypoglycemia, pancreatitis, injection-site reactions, or thyroid malignancy were reported. In summary, in Chinese participants with T2D, 24 weeks of bi-weekly bilpatide improved glycemic control and reduced body weight, with cardiometabolic benefits and acceptable safety and tolerability.ClinicalTrials.gov registration: NCT06254274.