Abstract
Background: Oral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world.
Methods: We retrospectively studied subjects >65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycosylated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65-74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity.
Results: We studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (−13.1 ± 7.5 mmol/mol and −3.0±2.4 kg, respectively; P<0.01). Although cognitive function was lower in the late older group (r=−0.57, P<0.01), changes in HbA1c showed no difference between the two subgroups (P=0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r=−0.49, P<0.05). Glycemic targets were more likely to be achieved (P<0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n=2, Late; n=4).
Conclusions: Oral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation in subjects of ≥75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence.