Obesity medications that act through gut-derived hormonal pathways include glucagon-like peptide-1 receptor agonists (GLP-1), dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GLP-1/GIP), and emerging triple glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide/glucagon receptor agonists. These therapies are increasingly prescribed for weight management and glycemic control, as well as for their cardiometabolic and renal benefits. While these medications offer substantial benefits to patients across multiple health conditions, their use in older adults warrants heightened scrutiny. Older adults face increased risks of sarcopenia and frailty, and evidence from major clinical trials suggests that a substantial proportion of medication-associated weight loss agents may result in loss of lean mass, potentially posing risks for this population. Other adverse effects that may be more consequential in older adults include dehydration, malnutrition, perioperative aspiration, and fat-predominant weight regain after discontinuation. This paper provides a clinically oriented framework to guide prescribing decisions for older adults. Drawing on patient scenarios from common geriatric contexts, including frailty, cognitive impairment, glucocorticoid use, and surgical planning, we propose prescribing approaches that optimize therapeutic benefits while mitigating potential harms. We integrate these recommendations within the Geriatrics 5Ms Framework (Mind, Mobility, Medications, Multicomplexity, and Matters Most) to contextualize treatment within geriatrics practice. Lifestyle co-interventions, particularly resistance training, adequate protein intake, and ongoing functional monitoring, emerge as essential components for older adults receiving these therapies. We also discuss identifying priority areas for future research, including age-stratified clinical trials and the routine inclusion of body composition and physical function outcomes.
