Efsubaglutide Alfa: A Comprehensive Pharmacological Review

Efsubaglutide alfa (also known as supaglutide) is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA) engineered as a GLP-1 analogue fused to a human immunoglobulin G2 (IgG2) fragment crystallisable (Fc) domain. This narrative review summarises published and publicly available evidence on efsubaglutide alfa pharmacology, pharmacokinetics/pharmacodynamics, dose-exposure-response relationships, drug-drug interaction potential, and clinical efficacy and safety in type 2 diabetes (T2D) and overweight/obesity. Efsubaglutide alfa has prolonged exposure (terminal half-life approximately 182-215 h) and low steady-state fluctuation, but dosing-interval selection should not be inferred from half-life alone. Available population pharmacokinetic and exposure-response analyses indicate that steady-state trough concentration is most informative for glycaemic response, whereas average and peak concentrations contribute to interpretation of weight response and gastrointestinal tolerability. Across available studies, predominantly conducted in Chinese populations, efsubaglutide alfa shows class-consistent improvements in glycaemic control and body weight, with gastrointestinal adverse events as the main tolerability limitation. Exploratory every 2-week dosing and post-discontinuation glycaemic durability findings remain hypothesis-generating. No head-to-head comparative trials dedicated cardiovascular or renal outcome trials, or large globally diverse datasets are yet available; therefore, the current evidence should be interpreted as a clinical pharmacology synthesis rather than a comparative positioning claim.