DeLuca A, Schultz A, Ofori H
… +3 more, Maggio V, Rizzo M, Rizvi AA
Expert Opin Drug Saf
· 2026 Jul · PMID 41289250
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INTRODUCTION: Insulin remains the mainstay of diabetes management. Once weekly insulins (OWI) being investigated as viable options for both type 1 and type 2 diabetes. Less frequent dosing and better pharmacokinetic prof...INTRODUCTION: Insulin remains the mainstay of diabetes management. Once weekly insulins (OWI) being investigated as viable options for both type 1 and type 2 diabetes. Less frequent dosing and better pharmacokinetic profile with these products hold the promise for improved patient adherence and enhanced efficacy in everyday practice. AREAS COVERED: We conducted a biomedical literature review of the PubMed database from 2009 to 2025. This narrative review summarizes the characteristics, advantages, and drawbacks of the two OWI products on the market and in development, namely insulin icodec and insulin efsitora. We review the published data with an emphasis on the safety of these when compared with daily long-acting insulin in insulin-treated and insulin-naïve patients with diabetes. EXPERT OPINION: The available data for OWI thus far points to similar adherence, acceptability, and efficacy when compared to once-daily insulin. OWI use was associated with comparable lowering of glycosylated hemoglobin and achievement of glycemic targets, potentially widening the treatment options for individuals with diabetes. However, increased risks of hypoglycemia and weight gain were seen in some studies. The clinical concerns regarding hypoglycemia led the U.S. regulatory agency to vote against recommending approval of icodec for use in patients with type 1 diabetes.
Xu B, Zhang T, He Y
… +4 more, Jiang A, Liu Y, He Z, Zhou J
Expert Opin Drug Saf
· 2025 Nov · PMID 41283794
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BACKGROUND: There is conflicting real-world evidence regarding the risk of breast and bladder cancer associated with sodium glucose cotransporter 2 (SGLT2) inhibitors. We conducted a pharmacovigilance study on SGLT2 inhi...BACKGROUND: There is conflicting real-world evidence regarding the risk of breast and bladder cancer associated with sodium glucose cotransporter 2 (SGLT2) inhibitors. We conducted a pharmacovigilance study on SGLT2 inhibitors and breast and bladder cancer using the US FDA Adverse Event Reporting System (FAERS) and a Mendelian randomization (MR) study. RESEARCH DESIGN AND METHODS: We used AERSMine to mine adverse events from FAERS. We provided proportional reporting ratio (PRR) with 95% confidence interval (CI), and the lower limit of the 95% credible interval of the information component (IC). A two-sample MR approach was used to investigate the causal relationship between SGLT2 inhibition and breast and bladder cancer. RESULTS: We did not find a disproportionate association between SGLT2 inhibitors (PRR = 1.26; 95%CI 1.05-1.51; = 0.014; IC = 0.01) and their molecules with breast cancer. SGLT2 inhibitors were associated with a disproportionately higher reporting frequency of bladder cancer events compared to metformin, dipeptidyl peptidase 4 inhibitors, or glucagon-like peptide-1 receptor agonists. MR analysis results showed that SGLT2 inhibition was associated with a higher risk of bladder cancer (odds ratio 1.01; 95%CI 1.00-1.01; = 0.004). CONCLUSION: Our results suggest that the use of SGLT2 inhibitors is associated with a higher reporting frequency/risk of bladder cancer, rather than breast cancer.
Li D, Li Y, Yao L
… +8 more, Li J, Zhou X, Gui M, Lu B, Chen X, Dong Y, Fu D, Wang M
Expert Opin Drug Saf
· 2025 Nov · PMID 41248909
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BACKGROUND: This study conducts a comprehensive comparative analysis of adverse event (AE) signals between sacubitril/valsartan and valsartan, two pivotal cardiovascular drugs for heart failure and hypertension, utilizin...BACKGROUND: This study conducts a comprehensive comparative analysis of adverse event (AE) signals between sacubitril/valsartan and valsartan, two pivotal cardiovascular drugs for heart failure and hypertension, utilizing the FAERS database to identify differential safety risks and optimize clinical monitoring. RESEARCH DESIGN AND METHODS: Data from the FAERS database (2004Q1-2024Q2) were analyzed using disproportionality analysis and Bayesian methods to detect and evaluate AE signals associated with sacubitril/valsartan and valsartan, enabling a comparative assessment. RESULTS: A total of 102,678 adverse event reports (AERs) were linked to sacubitril/valsartan, compared to 24,318 AERs for valsartan. Sacubitril/valsartan demonstrated the strongest association with cardiac disorders (ROR 4.13), while valsartan exhibited the highest association with vascular disorders (ROR 2.67). Common AE signals aligned with the respective drug labels. Unexpected AEs for sacubitril/valsartan included myocardial infarction ( = 2,909, ROR 6.45), arrhythmia ( = 1,691, ROR 4.07), decreased activity ( = 544, ROR 11.13), and fluid imbalance ( = 44, ROR 11.98). Unique AEs for valsartan included fear of disease ( = 137, ROR 47.57), thrombotic stroke ( = 31, ROR 25.60), merycism ( = 30, ROR 79.41), and eosinophilic colitis ( = 11, ROR 20.62). CONCLUSIONS: Sacubitril/valsartan and valsartan exhibit distinct AE risk profiles in cardiovascular disease treatment, underscoring the need for large-scale clinical trials and mechanistic studies on sacubitril to validate these findings.
McIntyre RS, Karpuram S, Farahmand K
… +6 more, Aldrich K, Bron M, Vanderhoef D, Thomas N, Jacobs M, Thai-Cuarto D
Expert Opin Drug Saf
· 2026 Jun · PMID 41212745
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INTRODUCTION: The United States Food and Drug Administration (FDA) requires post-marketing surveillance of approved drugs, and pharmaceutical manufacturers maintain comprehensive programs that include adverse event monit...INTRODUCTION: The United States Food and Drug Administration (FDA) requires post-marketing surveillance of approved drugs, and pharmaceutical manufacturers maintain comprehensive programs that include adverse event monitoring, internal safety assessments, and reporting to the FDA Adverse Events Reporting System (FAERS). AREAS COVERED: This report provides an overview of FAERS within the broader framework of post-marketing surveillance by pharmaceutical manufacturers. It also identifies several limitations to FAERS public dashboard data for safety analyses. A PubMed search for published findings of FAERS safety analyses with vesicular monoamine transporter 2 (VMAT2) inhibitors provide a case study that illustrates the need for careful interpretation based on the limitations of the FAERS database. EXPERT OPINION: Using a case study of VMAT2 inhibitors, we identified factors in data quality and manufacturer pharmacovigilance programs that must be considered when interpreting published analyses of FAERS public safety data. The application of artificial intelligence methodologies may prove helpful in identifying novel safety signals more accurately and more rapidly. At the same time, as clinicians consider individual treatment choices with their patients, discussion of safety data from the FAERS public dashboard should be contextualized within each drug's known safety profile.
Laudani C, Ortega-Paz L, Zgheib A
… +5 more, El Khoury G, Alawajneh M, Farahmandsadr M, Capodanno D, Angiolillo DJ
Expert Opin Drug Saf
· 2026 Jun · PMID 41211776
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INTRODUCTION: The landscape of oral anticoagulant (OAC) treatment dramatically changed with the introduction into clinical practice of the direct oral anticoagulants (DOACs), which have been able to overcome major limita...INTRODUCTION: The landscape of oral anticoagulant (OAC) treatment dramatically changed with the introduction into clinical practice of the direct oral anticoagulants (DOACs), which have been able to overcome major limitations of vitamin K antagonists. AREAS COVERED: This review summarizes the pharmacokinetic and pharmacodynamic profiles of commercially available DOACs (apixaban, rivaroxaban, dabigatran, and edoxaban), as well as their efficacy and safety in the settings of atrial fibrillation, venous thromboembolism, prevention of cancer-associated thrombotic events, and atherosclerotic disease. Limitations of commercially available DOACs are also reviewed. EXPERT OPINION: The introduction into clinical practice of DOACs has significantly changed the landscape of OAC, given their favorable safety and efficacy profiles. However, there are still several unmet needs for patients requiring treatment with OAC, underscoring the need for further research in the field to optimize the safety and efficacy of these agents across different clinical settings.
Hoffmann K, Michalak M, Rizzo M
… +2 more, Maggio V, Paczkowska A
Expert Opin Drug Saf
· 2026 Jun · PMID 41200927
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BACKGROUND: Tirzepatide has shown benefits in weight reduction and glycemic control in type 2 diabetes and obesity, but its relative efficacy and safety across doses remain unclear. METHODS: We conducted a PROSPERO-regis...BACKGROUND: Tirzepatide has shown benefits in weight reduction and glycemic control in type 2 diabetes and obesity, but its relative efficacy and safety across doses remain unclear. METHODS: We conducted a PROSPERO-registered systematic review and network meta-analysis of randomized controlled trials up to July 2024. Trials comparing tirzepatide (5, 10, or 15 mg weekly) with placebo, insulin, or GLP-1 receptor agonists in adults with type 2 diabetes and/or obesity were included. Random-effects models estimated mean differences (MDs) or relative risks (RRs), with treatment ranking assessed by SUCRA and evidence certainty rated with CINeMA. RESULTS: Thirteen RCTs (14,007 participants) were included. Tirzepatide produced dose-dependent weight reductions versus insulin (MD -14.5 kg for 15 mg; -12.5 kg for 10 mg; -10.2 kg for 5 mg; all < 0.0001). The likelihood of ≥15% weight loss (RR 4.83 for 15 mg), HbA1c reduction (MD -12.6 mmol/mol), and normoglycemia (RR 11.3) was significantly higher with tirzepatide. Safety analyses showed fewer serious adverse events (RR 0.71-0.77) and hypoglycemia (RR 0.44-0.50) than insulin, but more gastrointestinal events. CONCLUSIONS: Tirzepatide provides superior weight loss, glycemic improvements, and favorable safety versus insulin and other comparators, supporting its role as a leading therapy for type 2 diabetes and obesity.
Laudani C, Ortega-Paz L, Capodanno D
… +1 more, Angiolillo DJ
Expert Opin Drug Saf
· 2026 Apr · PMID 41194586
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INTRODUCTION: In patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention, 12 months of dual antiplatelet therapy (DAPT) with aspirin plus a P2Y inhibitor is the current standard. Howev...INTRODUCTION: In patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention, 12 months of dual antiplatelet therapy (DAPT) with aspirin plus a P2Y inhibitor is the current standard. However, DAPT is associated with an increased risk of bleeding. DAPT duration and intensity should be modulated according to the patient's specific risk profile to optimize outcomes. AREAS COVERED: Different DAPT regimens varying in intensity and duration have been shown to improve outcomes in specific settings. In patients at increased ischemic risk, DAPT escalation or prolongation can be considered, while de-escalation by discontinuing one of the antiplatelet drugs, reduction in the dose of the P2Y inhibitor, or switching to a less potent P2Y inhibitor should be considered in patients at increased risk of bleeding. Platelet function and genetic testing may help guiding the decision making. Antiplatelet agents also have specific drug-related adverse effects that clinicians should be aware of. EXPERT OPINION: Management of ACS patients has largely shifted over time, in order to achieve a patient-oriented approach. Development of specific scores based on genetic and clinical characteristics to predict patient's responsiveness to clopidogrel may allow to further reduce ischemic events, while technological and pharmacological advances are paving the way for further reduction of bleeding risk while preserving efficacy.
Expert Opin Drug Saf
· 2026 Apr · PMID 41173812
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INTRODUCTION: Placental abruption is a significant cause of fetomaternal mortality/morbidity. Management requires a difficult balance between opposing advantages/disadvantages for the fetus and mother. Remote from term,...INTRODUCTION: Placental abruption is a significant cause of fetomaternal mortality/morbidity. Management requires a difficult balance between opposing advantages/disadvantages for the fetus and mother. Remote from term, prompt delivery is best for the mother, but delayed delivery better for the fetus. AREAS COVERED: Prevalence of fetomaternal morbidity/mortality; range of clinical situations: certainty of diagnosis, gestational age, labor status, fetal condition/viability, presence of maternal shock/consumption coagulopathy, feasibility of prompt delivery. Pathophysiology: maternal hypovolaemia; abruption size; impairment of placental oxygenation; intrauterine tone and pressure; safety, efficacy, and application of tocolytic therapy to abruption; potential role of atosiban with emphasis on safety. EXPERT OPINION: The fetomaternal morbidity/mortality of placental abruption deserves consideration of further interventions that may improve fetomaternal outcome. More information is now available about signs/symptoms that do not require invasive diagnostic procedures. The contribution of maternal uterine hypertonus/tachysystole and increased uterine tone/pressure that affects fetal hypoxia/acidosis and consumption coagulopathy, strengthens the case for the use of a tocolytic to relax the uterus and improve fetal oxygenation. Due to its safety and efficacy profile, we make the case for atosiban as an agent to reduce uterine contractile frequency, tone, and pressure to improve fetal oxygenation and improve fetomaternal outcome.
Xie H, Dai R, Shi Y
… +5 more, Du X, Xu Z, Du X, Chen G, Zhao B
Expert Opin Drug Saf
· 2025 Oct · PMID 41121758
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BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are widely used, but may lead to significant serum creatinine elevation ( > 30%), posing a risk of acute kidney injury. RESEARCH DESIGN AND METHODS: A retros...BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are widely used, but may lead to significant serum creatinine elevation ( > 30%), posing a risk of acute kidney injury. RESEARCH DESIGN AND METHODS: A retrospective analysis was conducted using data from 3,720 hospitalized patients who received SGLT2i between 2014 and 2023. Patients were divided into two groups based on creatinine elevation ( > 30%). Univariate and multivariate logistic regression analyses were performed to identify risk factors, and a predictive model was constructed. The dataset of 1,040 patients from 2024 serves as validation data. RESULTS: Significant serum creatinine elevation ( > 30%) occurred in 6.67% of patients. Multivariate analysis identified nine risk factors: female sex, age ≥70 years, elevated admission serum creatinine, low admission plasma albumin, heart failure, and concomitant use of nephrotoxic antimicrobials, biologics, diuretics, or antiarrhythmic drugs. The predictive model demonstrated good discrimination (area under curve: 0.815) and calibration ( = 0.717), with consistent performance in the validation cohort (area under curve: 0.777). CONCLUSIONS: This study developed a reliable predictive model, highlighting key risk factors. The model can assist clinicians in early identification and monitoring of patients at risk, potentially reducing adverse renal outcomes and hospital stays. Further prospective studies are needed to validate and refine the model.
Expert Opin Drug Saf
· 2026 Apr · PMID 41099145
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INTRODUCTION: The rivastigmine transdermal patch was developed to provide similar efficacy to oral rivastigmine in the treatment of Alzheimer's disease (AD), but with improved tolerability. AREAS COVERED: Randomized clin...INTRODUCTION: The rivastigmine transdermal patch was developed to provide similar efficacy to oral rivastigmine in the treatment of Alzheimer's disease (AD), but with improved tolerability. AREAS COVERED: Randomized clinical trials and observational studies reporting on the tolerability of the rivastigmine transdermal patch in patients with AD, identified through a systematic literature search. EXPERT OPINION: Rivastigmine was the first cholinesterase inhibitor for which a transdermal formulation was developed; consequently, there is a substantial body of evidence on its efficacy and tolerability. The incidence of gastrointestinal AEs is markedly reduced with the transdermal patch compared with oral rivastigmine, while the efficacy of the patch remains similar to that of the oral formulation. Application site reactions are generally mild and do not cause much discomfort for the patient, and the risk of can be reduced by simple measures such as site rotation and good skin care. Tolerability of the patch improves over time, including at the highest dose level. Overall, the available evidence supports transdermal rivastigmine being generally well tolerated at doses up to 13.3 mg/24 h in patients with AD.
Expert Opin Drug Saf
· 2026 May · PMID 41098057
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INTRODUCTION: Most of the new agents in cancer therapy (referred to as targeted therapies in the paper) come to the market with limited and preliminary data concerning activity and tolerance. Although better tolerated th...INTRODUCTION: Most of the new agents in cancer therapy (referred to as targeted therapies in the paper) come to the market with limited and preliminary data concerning activity and tolerance. Although better tolerated than classical chemotherapy, safety issues of targeted agents must not be underestimated. AREAS COVERED: The aim of this mini review is to present some pharmacological specifities of targeted anticancer agents and to examine tolerance challenges observed after approval through some examples. References were identified through searches of PubMed for articles published up to March 2025 using the term postmarketing safety AND anticancer agent. Relevant articles were also searched for in high impact journals and specialty journals. EXPERT OPINION: Considering the clinical immaturity of targeted agents at their launch, partly due to expedited approvals, the new mechanisms of cell killing and the novel technologies of manufacturing, the postmarketing safety surveillance is a critical feature to secure their use. Pharmacoepidemiologic studies based on electronic health-based data will help to identify emergent and late safety events and to investigate their etiology along with predisposition factors. Work is also needed to elucidate the sex differences in toxicity of targeted therapies and to harmonize withdrawal decisions of drug regulatory agencies for safety reasons.
Gao Y, Pei J, Ji D
… +3 more, Chen Y, Huang Y, Wu A
Expert Opin Drug Saf
· 2025 Oct · PMID 41082243
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BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are frequently linked to gastrointestinal immune-related adverse events, which can severely affect patient outcomes. RESEARCH DESIG...BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are frequently linked to gastrointestinal immune-related adverse events, which can severely affect patient outcomes. RESEARCH DESIGN AND METHODS: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (2011-2024). Disproportionality analyses (ROR, PRR, BCPNN, MGPS) identified gastrointestinal adverse events (AEs) associated with ICIs across pan-cancer populations, while multivariable logistic regression and Bayesian network modeling were used to examine influencing factors. RESULTS: A total of 85 distinct gastrointestinal toxicities were identified and categorized as ICI-related gastrointestinal AEs (GI AEs). Substantial variation in ICI-related GI AE profiles was observed across different ICI regimens, with anti-CTLA-4 demonstrating the highest toxicity (ROR = 17.76 [16.88-18.68]). Logistic regression and Bayesian network analyses indicated that disease stage, concurrent targeted therapies, and ICI type significantly influenced the risk of developing ICI-related GI AEs. Patients with gastric variceal hemorrhage exhibited the highest mortality rate (63.64%). CONCLUSIONS: Our pharmacovigilance analysis reveals a high risk of gastrointestinal adverse events with ICI therapy, especially anti-CTLA-4. Stage IV disease, concurrent targeted therapies, and anti-CTLA-4 therapy or combination therapy further increase this risk, highlighting the need for personalized treatment strategies.