GLP-1 receptor agonists in older people with type 2 diabetes: safety evidence from the real world

GLP-1 receptor agonists (GLP-1RA) are glucose- and body weight-lowering therapies provided with cardio-renal benefits. Use of GLP-1RA in older adults with type 2 diabetes mellitus (T2DM) is increasing but concerns remain about their safety in this age group, particularly in light of multimorbidity, frailty, and polypharmacy, as well as age-related vulnerability to adverse events (AEs).

We discuss the opportunities and challenges of GLP-1RA in older people with T2DM, focusing on real-world (RW) safety evidence. Available RW studies confirm the established GLP-1RA safety profile, with AEs in 10-30% of older users, predominantly gastrointestinal and mild-to-moderate in severity. Age-stratified analyses provide mixed results on AE susceptibility, but discontinuation due to intolerance appears more frequent in older adults. Weight loss is preserved across age groups, with no consistent evidence of harmful unintended reductions. However, the effects on muscle mass and sarcopenia risk remain largely unexplored.

Current RW evidence supports GLP-1RA as a safe therapeutic option for older individuals with T2DM, without age-specific safety signals. Clinical phenotype-driven selection is essential to balance benefits and risks, particularly regarding nutritional status and frailty. Prospective, phenotype-stratified studies with body composition assessment are needed to guide optimal, individualized use in aging populations.