Safety profile of semaglutide in people aged 55 years and over: pooled data from the PIONEER, SUSTAIN and STEP phase 3 clinical programmes
Bibliographic record
Abstract
Abstract Background The 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. Method Safety 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). Result Data 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). Conclusion The 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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.017 | 0.021 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.010 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".