Abstract Aim To describe the design and rationale of LIGHT 2, a seamless, adaptive phase 2b/3 trial evaluating the efficacy and safety of efsubaglutide alfa for chronic weight management in adults with overweight or obesity. Materials and Methods LIGHT 2 is a multicentre, randomized, double‐blind, placebo‐controlled study in which eligible participants are assigned to efsubaglutide alfa dose regimens or matched placebo. Efsubaglutide alfa is administered with a prespecified dose‐escalation scheme to target maintenance doses delivered once weekly or once every 2 weeks. The seamless, adaptive framework enables interim evaluation to support regimen selection and progression to the confirmatory phase under a single protocol with maintained blinding and centralized oversight. An independent data monitoring committee reviews interim safety and adaptive decisions per a prespecified charter. Results The primary efficacy endpoint is percentage change in body weight. Key secondary endpoints include categorical weight‐loss thresholds, changes in anthropometric and cardiometabolic measures, and comprehensive safety and tolerability assessments; an imaging substudy will further characterize effects on ectopic fat in a subset of participants. Conclusions LIGHT 2 is designed to efficiently identify and confirm an efsubaglutide alfa regimen with clinically meaningful weight‐loss efficacy and an acceptable safety profile, while generating evidence relevant to real‐world implementation.
JIA et al. (2026) studied this question.