| アブストラクト | BACKGROUND: Obesity is a chronic and relapsing condition that affects all demographics and results in comorbidities, rising healthcare costs, and social challenges. Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a promising therapy offering significant weight reduction. However, uncertainty remains regarding its pancreatic and gallbladder safety profile across different populations and evidence sources. AIM: To systematically map existing evidence on the safety of tirzepatide in obesity management, with an emphasis on pancreatic- and gallbladder-related adverse events (AEs) across randomized controlled trials (RCTs), observational studies, case reports, and pharmacovigilance evidence. METHODS: Following the methodological framework of Arksey and O'Malley (2005), expanded with Joanna Briggs Institute guidance, this scoping review included RCTs, observational studies, and post-marketing safety reports identified between December 2019 and September 2025. The searches were conducted across PubMed, EMBASE, the Cochrane Library, and the FDA Adverse Event Reporting System (FAERS), with additional evidence identified through gray literature, targeted journal searches, and published pharmacovigilance studies based on the EudraVigilance database. ClinicalTrials.gov was subsequently searched as an additional source to identify relevant clinical trials. Studies were eligible if they examined pancreatic or gallbladder AEs in the context of tirzepatide exposure among individuals with obesity. The review included 11 RCTs, 5 observational studies, 4 case reports, 1 EudraVigilance pharmacovigilance analysis, and 575 FAERS reports. Pancreatic and gallbladder AEs were systematically extracted and coded using MedDRA version 28.1, following the predetermined hierarchy. Findings were mapped descriptively across data sources without formal comparative statistical testing. RESULTS: Pancreatic and gallbladder AEs were reported infrequently in RCTs. Pancreatitis was reported in 11 participants across five RCTs, with study-specific frequencies ranging from 0.2% (3 of 1,896) to 3.7% (1 of 27), while cholelithiasis was reported in 73 participants across 11 RCTs, with frequencies ranging from 0.3% (1 of 335 and 1 of 364) to 3.7% (1 of 27). Among observational studies, pancreatitis was reported in three studies, with proportions of 0.6% (63/10,002), 0.9% (1/110), and 2.1% (5,882/280,094). One retrospective cohort study reported an incidence rate of 3.84 events per 1,000 person-years among 9,193 participants, while cholelithiasis was reported at 11.89 events per 1,000 person-years in the same cohort. In the EudraVigilance pharmacovigilance analysis, pancreatitis represented 363 reported AEs (6.3% of all AEs and 19.4% of gastrointestinal AEs). In the FAERS database, pancreatitis accounted for 155/288 pancreatic-related reports [53.8%] and cholelithiasis for 143/249 gallbladder-related reports [57.4%]. Four case reports described six distinct AEs: edematous pancreatitis, acute pancreatitis, pancreatitis necrotizing, acalculous cholecystitis, gallstones, and gallbladder wall thickening, each reported once. Female participants, White participants, adults aged 18-64 years, and participants from the United States (US) predominated among reported demographic characteristics; however, demographic characteristics and comorbidity profiles were inconsistently reported and varied across studies. CONCLUSION: Pancreatic and gallbladder AEs were reported across clinical trials, observational studies, case reports, and pharmacovigilance databases. RCTs generally reported low frequencies of pancreatobiliary AEs, whereas pharmacovigilance databases captured a broader spectrum of reported events. Variability in study populations, comorbidity profiles, reporting methods, and the absence of exposure denominators limited direct comparison across evidence sources. Vigilant monitoring and standardized AE reporting are needed to further characterize the pancreatobiliary safety profile of tirzepatide. |
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| 組織名 | Pharmacovigilance Department, Macleods Pharmaceuticals Limited, Kyiv, Ukraine.;The University of Warwick, Coventry, UK.;University of Limerick, Limerick, Ireland.;Post Graduate Institute of Medical Education and Research, Chandigarh, India. |
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