Safety profile of semaglutide in people aged 55 years and over: pooled data from the PIONEER, SUSTAIN and STEP phase 3 clinical programmes

Abstract

AbstractBackgroundThe risk of Alzheimer’s disease (AD) increases with age. The glucagon‐like peptide‐1 analogue semaglutide, approved for type 2 diabetes (T2D) and overweight/obesity, is being investigated in the phase 3 evoke and evoke+ trials in people with early AD aged 55‐85 years. There is a need to summarise semaglutide weight loss efficacy and safety data in older populations. We investigated the safety of semaglutide in people with T2D and/or overweight/obesity ≥55 years using data from the phase 3a PIONEER, SUSTAIN and STEP clinical programmes.MethodSafety data for participants ≥55 years were pooled for: people with T2D receiving once‐daily oral semaglutide 3, 7 or 14 mg versus comparator (active or placebo) for 26‒78 weeks in PIONEER 1‒5 and 7‒10 (PIONEER pool, N = 4186); people with T2D receiving once‐weekly subcutaneous semaglutide 0.5 or 1 mg versus comparator (active or placebo) for 30‒56 weeks in SUSTAIN 1‒5 and SUSTAIN Japan (NCT02207374 and NCT02254291; SUSTAIN pool, N = 2825); and people with overweight/obesity (with/without T2D) receiving once‐weekly subcutaneous semaglutide 2.4 mg versus placebo for 68‒104 weeks in STEP 1‐6 (STEP pool, N = 1584).ResultData from 8595 participants were included. At baseline in the PIONEER, SUSTAIN and STEP pooled datasets, mean (standard deviation [SD]) age was 64.3 (6.4), 63.5 (6.1) and 62.0 (5.6) years, respectively, and mean (SD) body mass index was 30.8 (6.2), 31.0 (6.2) and 35.6 (6.2) kg/m2 (Table 1). The percentages of participants with adverse events (AEs) leading to treatment discontinuation in the semaglutide arms of PIONEER, SUSTAIN and STEP were 10.2, 9.1 and 7.7%, respectively, versus 5.2, 3.9 and 3.3% for the comparator arms (Table 2). Gastrointestinal disorders were the most frequently reported AE system organ class, with nausea, diarrhoea, constipation and vomiting the most frequent gastrointestinal AEs in the semaglutide arm of each pooled dataset (Table 2). Weight loss was greater with semaglutide versus comparator in all trials, with a tendency to plateau over time (Figure 1).ConclusionThe safety profile of semaglutide in participants ≥55 years is similar to that observed in the overall population, supporting the evaluation of semaglutide in an older population with early AD in evoke.