Safety considerations of semaglutide in the potential treatment of Alzheimer's disease: A pooled analysis of semaglutide in adults aged ≥ 65 years.

INTRODUCTION: The evoke/evoke+ trials are investigating semaglutide in a population with early Alzheimer's disease (AD). Specific analyses of semaglutide safety data in older adults are limited; therefore, in the current analysis, we aimed to evaluate safety considerations with semaglutide in adults ≥ 65 years. METHODS: Adverse event (AE) data from three semaglutide phase 3a programs in participants ≥ 65 years with type 2 diabetes and/or overweight/obesity were pooled. Change in body weight was also assessed in a smaller subset of participants ≥ 65 years. RESULTS: The analysis included 3529 participants ≥ 65 years. Baseline mean age and body mass index in participants ≥ 65 years were 69.3 to 70.2 years and 29.7 to 35.4 kg/m, respectively, compared to 47.8 to 58.5 years and 31.3 to 36.7 kg/m in the overall population. AEs with semaglutide occurred in 73.6% to 92.4% of participants ≥ 65 years versus 73.2% to 90.8% of the overall population. AEs with semaglutide leading to permanent discontinuation appeared to be more frequent in participants ≥ 65 years (9.3%-12.4%) versus the overall population (5.7%-8.7%). Gastrointestinal disorders were the most frequently reported AEs with semaglutide in participants ≥ 65 years (44.6%-73.8%) and in the overall population (39.1%-73.4%). Participants aged ≥ 65 years receiving semaglutide had an estimated weight loss of 3.8% at week 52 compared to 0.1% with placebo. DISCUSSION: Age ≥ 65 years did not appear to affect the safety considerations of semaglutide. The ongoing evoke/evoke+ trials will elucidate the balance of efficacy and safety in the treatment of early AD with semaglutide. HIGHLIGHTS: This was a post hoc analysis evaluating adverse event (AE) data of semaglutide in people ≥ 65 years.The most common AE with semaglutide was gastrointestinal (GI).GI event rates were similar in people ≥ 65 years and the overall study populations.