Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system

Abstract

BackgroundSemaglutide was approved for treatment of type 2 diabetes mellitus (T2DM) and chronic weight management in obesity or overweight adults. However, real-world data regarding its long-term gastrointestinal safety and tolerability in large sample population are incomplete. We evaluated semaglutide-associated gastrointestinal safety signals by data mining of the FDA pharmacovigilance database.MethodsReporting odds ratio (ROR) was employed to quantify the signals of semaglutide-related gastrointestinal adverse events (AEs) from 2018 to 2022. Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (χ2) test, and signals were prioritized using a rating scale.ResultsWe identified 5,442 cases of semaglutide-associated gastrointestinal AEs, with 45 signals detected, ranging from a ROR025 of 1.01 (hypoaesthesia oral) to 42.03 (eructation), among which 17 AEs were identified as new and unexpected signals. Patient age (p < 0.001) and body weight (p = 0.006) rather than sex (p = 0.251) might be associated with an increased risk of gastrointestinal AEs severity. Notably, the association between semaglutide and gastrointestinal disorders remained when stratified by age, body weight, sex and reporter type. One strong, 22 moderate and 22 weak clinical priority signals were defined. The median time-to-onset (TTO) for strong clinical priority signal was 23 days, while for moderate and weak, they were 6 and 7 days, respectively. All of the disproportionality signals had early failure type features, suggesting that the risk of gastrointestinal AEs occurrence gradually decreased over time.ConclusionOur study provided a deeper and broader understanding of semaglutide's gastrointestinal safety profiles, which would help healthcare professionals to mitigate the risk of gastrointestinal AEs in clinical practice.

The Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists in the Standard of Care Treatment of Type 2 Diabetes Mellitus

“…For retinopathy, this has been shown in PIONNER for semaglutide [ 31 ], and for pancreatitis, in PIONNER for semaglutide, in AWARD for dulaglutide, and in LEADER for liraglutide [ 31 , 72 , 73 ]. Gastrointestinal AEs, such as nausea, diarrhea, and vomiting, are higher in some studies [ 62 ], while in PIONNER for semaglutide, they have a similar incidence with placebo groups, or are majority mild forms, as in STEP for semaglutide [ 31 , 74 ].…”

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience

“…7 The most frequent adverse events in the present study were gastrointestinal, such as nausea (reported by 30% of patients). Gastrointestinal side-effects were expected, due to the results of previous studies, [15][16][17] and patients were warned of the possibility of their appearance. Importantly, these side-effects did not cause discontinuation of treatment.…”

Appendicitis: A Hidden Danger of GLP-1 Receptor Agonists?

“…12,13 Last, a recent pharmacovigilance study based on the Food and Drug Administration (FDA) adverse event reporting system (FAERS) reports 10 cases of serious (0.56%) and 2 cases of nonserious appendicitis (0.05%) associated with semaglutide over the span of 2018 to 2022. 14 One mentionable limitation of the literature is that there are little to no details on the acuity and outcomes of appendicitis, nor specific mentioning on timing and dosage relative to the adverse event to better gauge a correlation. The treatment method, including whether or not an appendectomy was performed, and type of surgery remain unknown in the bulk of the literature.…”

“…12,13 Last, a recent pharmacovigilance study based on the Food and Drug Administration (FDA) adverse event reporting system (FAERS) reports 10 cases of serious (0.56%) and 2 cases of nonserious appendicitis (0.05%) associated with semaglutide over the span of 2018 to 2022. 14…”