Real-world clinical outcomes of tirzepatide administration in older patients with type 2 diabetes, with a focus on the risk of hypoglycemia and weight loss-related parameters.

In an aging society, the establishment of safe and effective treatment strategies for older patients with type 2 diabetes is crucial. We performed a secondary analysis of the Hokkaido-TZP study (UMIN000056962), evaluating the real-world outcomes of tirzepatide in patients aged ≥65 years. Of 213 patients in the safety analysis set, 11 (5.2%) discontinued treatment because of adverse events, primarily gastrointestinal symptoms. In the effectiveness analysis set (n = 199; mean age 71.3 years, glycated hemoglobin [HbA1c] 7.79%), tirzepatide significantly reduced both HbA1c and body mass index over 6 months in the Young-old (65-74 years) and Old-old (≥75 years) groups. Notably, even among the 148 patients (74.4%) using agents associated with a risk of hypoglycemia (insulin, sulfonylureas, or glinides) at baseline, a substantial proportion (66.9%) achieved an HbA1c <7.0%. The physicians proactively adjusted these concomitant medications in 39.2% of users, but despite these preemptive reductions, this subgroup still achieved a reduction in HbA1c comparable to that of the entire cohort, and no severe hypoglycemia was reported. A significant reduction in body weight occurred, and this was more pronounced in glucagon-like peptide-1 receptor agonist-naïve patients and those taking fewer hypoglycemia-inducing agents. Furthermore, the tirzepatide dose tended to be lower in the patients who achieved greater weight loss. These findings suggest that although tirzepatide is highly effective, even in older adults, its safety must be optimized through preemptive reductions in the doses of concomitantly administered secretagogues and careful monitoring, to prevent excessive reductions in HbA1c and weight loss in this vulnerable population.