Table 3:
Adverse events during the on-treatment period in the pooled STEP-HFpEF and STEP-HFpEF DM populations
| Semaglutide group (n=573) |
Placebo group (n=572) |
|||||
|---|---|---|---|---|---|---|
| n (%) | Events (n) | Events (per 100 person-years) | n (%) | Events (n) | Events (per 100 person-years) | |
| Serious adverse events | 90 (16%) | 161 | 28·7 | 159 (28%) | 301 | 52·7 |
| Serious adverse events leading to treatment discontinuation | 12 (2%) | 13 | 2·3 | 17 (3%) | 21 | 3·7 |
| Serious gastrointestinal disorders leading to treatment discontinuation | 2 (<1%) | 2 | 0·4 | 1 (<1%) | 1 | 0·2 |
| Adverse events leading to treatment discontinuation | 68 (12%) | 92 | 16·4 | 39 (7%) | 51 | 8·9 |
| Gastrointestinal disorders leading to treatment discontinuation | 45 (8%) | 60 | 10·7 | 16 (3%) | 19 | 3·3 |
| Fatal events | 7 (1%) | 7 | 1·25 | 12 (2%) | 17 | 3·0 |
| Most frequent serious adverse by system organ class* | ||||||
| Cardiac disorders | 26 (5%) | 31 | 5·5 | 70 (12%) | 101 | 17·7 |
| Atrial fibrillation | 8 (1%) | 8 | 1·4 | 15 (3%) | 20 | 3·5 |
| Cardiac failure | 3 (1%) | 3 | 0·5 | 34 (6%) | 43 | 7·5 |
| Cardiac failure congestive | 1 (<1%) | 1 | 0·2 | 6 (1%) | 6 | 1·1 |
| Infections and infestations | 16 (3%) | 22 | 3·9 | 44 (8%) | 60 | 10·5 |
| Gastrointestinal disorders | 12 (2%) | 14 | 2·5 | 12 (2%) | 13 | 2·3 |
| Nervous system disorders | 14 (2%) | 15 | 2·7 | 13 (2%) | 14 | 2·5 |
| Renal and urinary disorders | 8 (1%) | 9 | 1·6 | 12 (2%) | 14 | 2·5 |
| Vascular disorders | 7 (1%) | 7 | 1·3 | 7 (1%) | 7 | 1·2 |
| Respiratory, thoracic, and mediastinal | 6 (1%) | 6 | 1·1 | 16 (3%) | 18 | 3·2 |
| Musculoskeletal and connective tissue | 9 (2%) | 11 | 2·0 | 12 (2%) | 13 | 2·3 |
| Injury, poisoning, and procedural | 11 (2%) | 15 | 2·7 | 6 (1%) | 7 | 1·2 |
| Metabolism and nutrition disorders | 6 (1%) | 6 | 1·1 | 8 (1%) | 8 | 1·4 |
| Hepatobiliary disorders | 4 (1%) | 7 | 1·3 | 4 (1%) | 7 | 1·2 |
| General disorders and administration site | 2 (<1%) | 2 | 0·4 | 6 (1%) | 6 | 1·1 |
| Neoplasms benign, malignant, and unspecified | 9 (2%) | 9 | 1·6 | 10 (2%) | 10 | 1·8 |
| Safety focus areas† | ||||||
| COVID-19-related events‡ | 73 (13%) | 73 | 13·0 | 80 (14%) | 85 | 14·9 |
| Serious cardiovascular disorders | 45 (8%) | 55 | 9·8 | 92 (16%) | 135 | 23·6 |
| Serious gastrointestinal disorders | 12 (2%) | 14 | 2·5 | 12 (2%) | 13 | 2·3 |
| Medication errors‡ | 2 (<1%) | 2 | 0·4 | 6 (1%) | 7 | 1·2 |
| Serious neoplasms | 11 (2%) | 11 | 2·0 | 15 (3%) | 15 | 2·6 |
| Serious acute gallstone disease | 4 (1%) | 7 | 1·3 | 5 (1%) | 8 | 1·4 |
| Serious acute renal failure | 7 (1%) | 8 | 1·4 | 8 (1%) | 9 | 1·6 |
| Serious malignant neoplasms | 8 (1%) | 8 | 1·4 | 10 (2%) | 10 | 1·8 |
| Serious hepatic disorders | 0 | 0 | ·· | 1 (<1%) | 1 | 0·2 |
| Serious allergic reactions | 0 | 0 | ·· | 2 (<1%) | 2 | 0·4 |
| Acute pancreatitis‡ | 1 (<1%) | 1 | 0·2 | 1 (<1%) | 1 | 0·2 |
| Serious rare events | 1 (<1%) | 1 | 0·2 | 1 (<1%) | 1 | 0·2 |
| Serious hypoglycaemia | 1 (<1%) | 1 | 0·2 | 0 | 0 | ·· |
| COVID-19-related deaths | 1 (<1%) | 1 | 0·2 | 1 (<1%) | 1 | 0·2 |
| Adjudicated events§ | ||||||
| All-cause death | 8 (1%) | 8 | 1·3 | 14 (2%) | 14 | 2·3 |
| Cardiovascular death | 2 (<1%) | 2¶ | 0·3 | 5 (1%) | 5 | 0·8 |
| Heart failure events | 8 (1%) | 10 | 1·6 | 30 (5%) | 36 | 5·8 |
Data are adverse events during the on-treatment period in the safety analysis set, which included all randomly assigned participants who received at least one dose of semaglutide or placebo (all participants received at least one dose, and thus the safety analysis set was the same as the full analysis set). The on-treatment period spans from the date of first administration of semaglutide or placebo to the date of the last administration of semaglutide or placebo (excluding potential off-treatment time if two or more consecutive doses were missed). For the assessment of adverse events, each on-treatment period extends for 35 days from the date of most recent drug administration, unless otherwise stated. Investigators could report more than one event with a fatal outcome for the same participant. No treatment misuse was reported in either trial.
As per the Medical Dictionary for Regulatory Activity; adverse events occurring in ≥1% of participants in any treatment group are shown.
On the basis of therapeutic experience with GLP-1 receptor agonists and regulatory feedback and requirements, several safety focus areas (both serious and non-serious adverse events) were prespecified as being of special interest in the safety assessment; these preferred terms, identified through predefined searches of the Medical Dictionary for Regulatory Activity, were judged relevant for each of the safety focus areas.
Safety focus areas in STEP-HFpEF DM only.
Data are for the in-trial period (ie, the time from random assignment to last contact with a trial site, irrespective of treatment discontinuation or rescue intervention).
Includes one death of undetermined cause.