Difference in Gastrointestinal Risk Associated with Use of GLP-1 Receptor Agonists: A Real-World Pharmacovigilance Study

Abstract

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are promising weight-loss drugs, but real-world data concerning the liability of GLP-1RAs in gastrointestinal safety are lacking. We examined the differences in gastrointestinal safety between semaglutide and liraglutide. Materials and Methods: We used the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and retrieved data during the first three years of semaglutide and liraglutide approved by the FDA. Thirteen main gastrointestinal adverse drug reactions (GADRs) were evaluated. Patient demographics, treatment information, and outcome of events were summarized. Disproportionality analyses were conducted by estimating the reporting odds ratios (RORs) and 95% confidence intervals (CIs). Results: In the reported cases of semaglutide (n = 2047) and liraglutide (n = 4175), semaglutide had a higher pooled ROR and later pooled time-to-onset median of GADRs compared with those of liraglutide (5.53, 95% CI 5.23-5.85 vs 3.95, 95% CI 3.81-4.10; 7 days, Q1-Q3: 0-48 vs 4 days, Q1-Q3: 0-34.5). The thirteen GADRs associated with these two GLP-1RAs showed a significant difference in the profile of reporting risk and time-to-onset. Conclusion: GLP-1RAs produce a spectrum of distinct classes of GADRs. The individual properties of GADRs between semaglutide and liraglutide might enable incretin-based treatment of obesity to be "tailored" to the needs of each patient.

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

“…The data on time-to-onset for moderate AEs signals were not significantly different from a recent study, indicating the median durations of nausea, diarrhea and vomiting were 8, 3, and 2 days respectively, in the semaglutide 2.4 mg arm ( 26 ). A real-world pharmacovigilance study of semaglutide had also demonstrated a similar pooled median time-to-onset of gastrointestinal AEs (7 days, IQR 0–48 days), which further supported the findings of our analysis ( 13 ). Hence, careful monitoring in the early period following semaglutide administration might detect most gastrointestinal AEs.…”

“…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. Semaglutide-associated gastrointestinal AEs seemed to predominately affect females (57.68%) ( Table 1 ), which was in line with the finding that gastrointestinal risks in T2DM occurred more often in females (52.32%) ( 13 ). Further comparison of serious and non-serious cases showed that the proportion of serious AEs was similar in males and females (33.81 vs. 32.31%), and there was no statistical difference between the two groups ( p = 0.251).…”

“…These gastrointestinal symptoms are thought to be related to GLP-1RA activating central and peripheral GLP-1 receptors and delaying gastric emptying ( 25 ). In a previous study, only 13 semaglutide-associated gastrointestinal AEs were reported in 2018–2020 from the FAERS database ( 13 ), while 45 significant AEs with at least ten reports were detected in our study, among which 17 AEs were identified as new and unexpected signals. The full list of all new semaglutide-associated gastrointestinal AEs was shown in Figure 2 .…”

“…Considering the increased number of approved indications and widespread use of semaglutide, gastrointestinal AEs reported a remarkable increase from 2018 to 2021, with the annual reports in 2021 ( n = 1,847) almost 4 times of 2018 ( n = 454). A total of 5,442 reports of semaglutide-related gastrointestinal AEs were retained in our study, while Zhou et al ( 13 ) reported only 2,047 cases, and the number of cases reported in each year was unknown. Based on our data prediction, reports of semaglutide will continue to increase in 2022, as there are 949 cases in the first quarter of 2022 alone, which is far above the average quarterly number for 2018–2021.…”

“…A systematic review and network meta-analysis published in 2014 revealed that, all GLP-1RAs dose regimens distinctly increased the incidence of gastrointestinal AEs compared with placebo or conventional treatment ( 7 ). Another previous real-world disproportionality analysis of GLP-1RAs-associated gastrointestinal AEs based on the FDA Adverse Event Reporting System (FAERS) from 2018 to 2020 included 2,047 cases of semaglutide and 4,075 cases of liraglutide for the treatment of obesity ( 13 ). This study demonstrated that semaglutide had a higher pooled ROR and later pooled time-to-onset median of gastrointestinal AEs compared with those of liraglutide.…”