Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and multi-incretin therapies have transformed the management of obesity, but concerns remain regarding the potential musculoskeletal consequences of accompanying reductions in lean (muscle) mass, particularly among older adults. Available studies, predominantly using DXA, show absolute lean soft tissue mass losses of up to 6.5 kg, typically representing ~25–35% of total weight loss, although relative lean mass may increase due to preferential fat mass loss. MRI studies also demonstrate reductions in muscle volume, accompanied by marked improvements in muscle fat infiltration, but the magnitude of muscle loss is generally proportional to total weight loss, implying there is no disproportionate drug effect. However, there is currently no consensus on what constitutes a clinically harmful degree of muscle loss, which likely varies by age and baseline levels. At present, the long-term effects of incretin-based weight loss on sarcopenia, falls and frailty risk remain uncertain, but available evidence suggests that muscle strength and function are generally preserved or improved. However, greater losses have been reported among older adults with sarcopenia treated with semaglutide. Evidence regarding hip and lumbar spine BMD is limited, with no consistent adverse effects demonstrated to date. Findings for fracture risk remain mixed, but some studies suggest a potential increased risk among older adults. Collectively, interpretation of the effects of incretin-mimetics therapies on musculoskeletal outcomes is complicated by heterogeneity in participant characteristics, incretin-mimetics agents, weight loss magnitude, outcome-assessment methods, and follow-up duration. Nevertheless, to help preserve musculoskeletal health outcomes, it is recommended incretin-mimetic therapy be combined with resistance training, aerobic and weight-bearing activity, along with adequate protein intake (1.2–1.6 g/kg/day). This presentation will critically evaluate the evidence underpinning these recommendations and examine the potential of digital health technologies to remotely deliver and monitor evidence-based exercise and lifestyle programs.