Abstract
GLP-1 is an incretin hormone with broad pharmacological potential. GLP-1 receptor agonists (GLP-1RA) are successfully in clinical use for T2D and obesity. Several GLP-1-based therapies are in clinical evaluation for treating metabolic diseases. Supaglutide (supa), a novel GLP-1RA, is in late-stage clinical investigation for T2D. The efficacy and safety are being investigated in 340 patients with T2D inadequately controlled on metformin in this randomized, double-blind, placebo-controlled phase 3 clinical trial (NCT04998032). Supa 3 mg QW treatment resulted in a statistically significant reduction in HbA1c of -1.81% from baseline at week 24 (p<0.001). Body weight was decreased by 3.80% from baseline in supa 3 mg group, with a significant difference versus placebo group (p<0.001). Supa also significantly improved glucose excursion, and increased meal-stimulated insulin and C-peptide secretion as determined by MMTT, suggesting improved glucose tolerance and enhanced β-cell function. Overall TEAEs occurred in 66.7% and 73.4% with placebo and supa 3 mg, respectively. The most common TEAEs with supa were GI symptoms, such as nausea, vomiting, diarrhea and decreased appetite mostly in mild or moderate severity. Supa 3 mg improved glycemic and metabolic control and was well tolerated in T2D inadequately controlled on metformin, suggesting supa as a novel alternative therapy for T2D and metabolic disorders.