Dataset Information

Long-Term Safety and Efficacy of Sitagliptin for Type 2 Diabetes Mellitus in Japan: Results of a Multicentre, Open-Label, Observational Post-Marketing Surveillance Study.

ABSTRACT:

Introduction

A post-marketing surveillance (PMS) study was conducted to confirm the long-term risk-benefit profile of sitagliptin administered to Japanese patients with type 2 diabetes mellitus (T2DM) under real-world conditions.

Methods

This prospective, multicentre, open-label PMS collected data from 3326 patients receiving sitagliptin according to the approved indication during the case registration period (July 2010-June 2012; observation period, 3 years). Safety was assessed via collection of data on adverse drug reactions (ADRs), estimated glomerular filtration rate (eGFR) and cardiovascular events whereas efficacy was assessed via changes in glycated hemoglobin (HbA1c).

Results

In 3265 patients evaluated for safety, 270 ADRs occurred in 207 (6.3%) patients overall. Metabolism and nutrition disorders were the most common class of ADRs, occurring in 58 patients overall (53 non-serious, 5 serious) with hypoglycaemia (17 patients, 0.52%) the most common ADR. In patients with eGFR > 90 mL/min/1.73 m² at baseline (mean ± SD, 106.42 ± 18.11 mL/min/1.73 m², n = 584), eGFR declined by 11.83 ± 17.53 mL/min/1.73 m² (P < 0.0001; n = 360) over the observation period whereas eGFR appeared to be relatively maintained in patients with lower baseline eGFR levels. Cardiovascular events were infrequent [occurring in 4 of 84 (4.76%) patients at high cardiovascular risk] with no distinct features in this Japanese population and the cumulative incidence [8.42% (3.12-21.70) at 36 months; n = 32] was similar to that noted in previous studies involving sitagliptin. In patients evaluated for efficacy, the overall change in HbA1c from baseline to final evaluation was mean ± SD - 0.68 ± 1.34% (P < 0.0001, n = 2070). Reductions in HbA1c tended to be greater in younger patients and patients with higher body mass index (BMI) and HbA1c values at the start of administration.

Conclusion

Long-term sitagliptin administration in the routine clinical practice setting is associated with good efficacy, including as monotherapy, with no additional safety concerns.

SUBMITTER: Yoshikawa K

PROVIDER: S-EPMC7467485 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-Term Safety and Efficacy of Sitagliptin for Type 2 Diabetes Mellitus in Japan: Results of a Multicentre, Open-Label, Observational Post-Marketing Surveillance Study.

Yoshikawa Ken K Tsuchiya Akira A Kido Tomoyuki T Ota Tomohiro T Ikeda Keiko K Iwakura Mika M Maeda Yoshikazu Y Maekawa Shinichiroh S

Advances in therapy 20200418 5

<h4>Introduction</h4>A post-marketing surveillance (PMS) study was conducted to confirm the long-term risk-benefit profile of sitagliptin administered to Japanese patients with type 2 diabetes mellitus (T2DM) under real-world conditions.<h4>Methods</h4>This prospective, multicentre, open-label PMS collected data from 3326 patients receiving sitagliptin according to the approved indication during the case registration period (July 2010-June 2012; observation period, 3 years). Safety was assessed ...[more]

PMID: 32306246

Similar Datasets

Project description:IntroductionTeneligliptin/canagliflozin combination tablets, which combine a dipeptidyl peptidase-4 (DPP-4) inhibitor (teneligliptin) and a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin), are a treatment option for type 2 diabetes mellitus (T2DM) in Japan. This post-marketing surveillance evaluated the real-world safety and effectiveness of teneligliptin/canagliflozin combination tablets, and changes in self-reported adherence to oral antihyperglycaemic agents.MethodsJapanese patients with T2DM who were prescribed the combination tablets for the first time between December 2017 and June 2018 were registered and followed up for 12 months. Safety and effectiveness were assessed in terms of adverse drug reactions (ADRs) and the changes in haemoglobin A1c (HbA1c) and body weight from baseline to 12 months with the last observation carried forward, respectively. Adherence was assessed using the Morisky Medication Adherence Scale 8.ResultsOverall, 821 patients were eligible for the analyses, including 733 who were prescribed the combination tablets for 12 months. ADRs and serious ADRs were reported in 4.38% and 0.85% of patients, respectively. Gastrointestinal disorders (0.97%) were the most common class of ADRs. No new safety concerns were identified beyond those described in the Japanese package insert. The changes in HbA1c and body weight from baseline to 12 months were - 0.43 ± 0.93% and - 1.29 ± 5.57 kg, respectively. The reductions in HbA1c at 12 months tended to be greater among patients who switched from either DPP-4 inhibitors (- 0.71 ± 0.89%) or SGLT2 inhibitors (- 0.51 ± 1.00%) relative to patients who switched from both (- 0.22 ± 0.88%). The decrease in body weight was greatest among patients who switched from DPP-4 inhibitors. An improvement in self-reported adherence to oral antihyperglycaemic agents occurred after switching to the combination tablets.ConclusionTeneligliptin/canagliflozin combination tablets were effective and associated with an improvement in adherence without new safety concerns in Japanese patients with T2DM in real-world clinical practice.Trial registrationJapicCTI-173778.

Project description:IntroductionAs a result of the well documented limitations of data collected by spontaneous reporting systems (SRS), such as bias and under-reporting, a number of authors have evaluated the utility of other data sources for the purpose of pharmacovigilance, including the biomedical literature. Previous work has demonstrated the utility of literature-derived distributed representations (concept embeddings) with machine learning for the purpose of drug side-effect prediction. In terms of data sources, these methods are complementary, observing drug safety from two different perspectives (knowledge extracted from the literature and statistics from SRS data). However, the combined utility of these pharmacovigilance methods has yet to be evaluated.ObjectiveThis research investigates the utility of directly or indirectly combining an observational signal from SRS with literature-derived distributed representations into a single feature vector or in an ensemble approach for downstream machine learning (logistic regression).MethodsLeveraging a recently developed representation scheme, concept embeddings were generated from relational connections extracted from the literature and composed to represent drug and associated adverse reactions, as defined by two reference standards of positive (likely causal) and negative (no causal evidence) pairs. Embeddings were presented with and without common measures of observational signal from SRS sources to logistic regressors, and performance was evaluated with the receiver operating characteristic (ROC) area under the curve (AUC) metric.ResultsROC AUC performance with these composite models improves up to ≈ 20% over SRS-based disproportionality metrics alone and exceeds the best prior results reported in the literature when models leverage both sources of information.ConclusionsResults from this study support the hypothesis that knowledge extracted from the literature can enhance the performance of SRS-based methods (and vice versa). Across reference sets, using literature and SRS information together performed better than using either source alone, providing strong support for the complementary nature of these approaches to post-marketing drug surveillance.

Project description:Background and objective: Sacituzumab govitecan (SG), the first antibody-drug conjugate targeting human trophoblast cell-surface antigen 2 (Trop-2), has been approved by the Food and Drug Administration (FDA) for the treatment of advanced or metastatic breast cancer and urothelial cancer. However, there is currently a dearth of information regarding the safety profiles of SG in a large sample cohort. The objective of the present study is to investigate SG-related adverse events (AEs) in real-world settings leveraging the FDA Adverse Event Reporting System (FAERS) database to guide the safety management of clinical medication. Methods: The FAERS database was retrospectively queried to extract reports associated with SG from April 2020 to March 2023. To identify and evaluate potential AEs in patients receiving SG, various disproportionality analyses such as reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed. Results: Overall, 2069 reports of SG as the "primary suspect" were identified. Noteworthy, SG was significantly associated with an increased risk of blood lymphatic system disorders (ROR, 7.18; 95% CI, 6.58-7.84) and hepatobiliary disorders (ROR, 2.68; 95% CI, 2.17-3.30) at the System Organ Class (SOC) level. Meanwhile, 61 significant disproportionality preferred terms (PTs) simultaneously complied with all four algorithms were adopted. Therein, anemia, thrombocytopenia, neutropenia, leukopenia, diarrhea, asthenia, alopecia, and electrolyte imbalance were consistent with the common AEs described in the clinical trials and specification of SG. Furthermore, unexpected significant AEs include colitis (ROR, 12.09; 95% CI, 9.1-16.08), heart rate increased (ROR, 5.11; 95% CI, 3.84-6.79), sepsis (ROR, 4.77; 95% CI, 3.59-6.34), cholestasis (ROR, 6.28; 95% CI, 3.48-11.36), blood bilirubin increased (ROR, 4.65; 95% CI, 2.42-8.94) and meningitis (ROR, 7.23; 95% CI, 2.71-19.29) were also be detected. The median time to onset of SG-related AEs was 14 [interquartile range (IQR), 7-52] days, with the majority occurring within the initial month of SG treatment. Conclusion: Our study validates the commonly known AEs and also found some potentially emerging safety issues related to SG in real-world clinical practice, which could provide valuable vigilance evidence for clinicians and pharmacists to manage the safety issues of SG.

Project description:IntroductionThis long-term post-marketing surveillance (SAPPHIRE) collected information on the safety and effectiveness of canagliflozin (approved dose 100 mg) prescribed to patients with type 2 diabetes mellitus (T2DM) in real-world practice in Japan.MethodsPatients with T2DM who were prescribed canagliflozin between December 2014 and September 2016 were registered and observed for up to 3 years. Safety was evaluated in terms of adverse drug reactions (ADRs). Effectiveness was assessed in terms of glycaemic control. Data were also analysed across age subgroups (< 65, ≥ 65 to < 75, and ≥ 75 years old) and the estimated glomerular filtration rate (eGFR) categories for chronic kidney disease (G1-G5 based on eGFR) at baseline.ResultsA total of 12,227 patients were included in the safety analyses and 11,675 in effectiveness analyses. Overall, 7104 patients were treated with canagliflozin for ≥ 3 years. The mean age, haemoglobin A1c (HbA1c), and eGFR at baseline were 58.4 ± 12.5 years, 8.01 ± 1.49%, and 80.04 ± 21.85 mL/min/1.73 m2, respectively. There were 1836 ADRs in 1312 patients (10.73%) and 268 serious ADRs in 225 patients (1.84%). The most common ADRs were those related to volume depletion (1.39%), genital infection (1.34%), polyuria/pollakiuria (1.23%), and urinary tract infection (1.19%). The frequencies of ADRs tended to increase with age and stage of chronic kidney disease. The reductions in mean HbA1c after starting canagliflozin were maintained for up to 3 years with a mean change of - 0.68% (n = 6345 at 3 years). Maintained reductions in mean HbA1c were observed in each age subgroup and in patients with G1-G3b renal function.ConclusionThis surveillance in real-world clinical practice showed that canagliflozin provides sustained glucose-lowering effects in patients with T2DM, including elderly patients and patients with moderate renal impairment, without new safety concerns beyond those already described in the Japanese package insert.Trial registrationJapicCTI-153048.

Project description:BackgroundNivolumab has been approved for treating ≥ 10 cancer types. However, there is limited information on the incidence of rare, but potentially serious, treatment-related adverse events (TRAEs), as well as notable TRAEs in patients with certain medical disorders or older patients in Japan.MethodsWe performed pooled analyses of data from published post-marketing surveillance in Japan of nivolumab monotherapy for patients with malignant melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancer, and gastric cancer to determine the frequencies of 20 categories of TRAEs of special interest overall and in patient groups with higher perceived safety risks (history of autoimmune disease, interstitial lung disease, tuberculosis, or hepatitis B/C; patients vaccinated during nivolumab treatment; and older patients [≥ 75 years]).ResultsThe overall population comprised 7421 patients treated with nivolumab. TRAEs were reported in 49.1% of patients, with grade ≥ 3 TRAEs in 16.7%. Endocrine disorders (14.4%), hepatobiliary disorders (10.9%), and interstitial lung disease (7.0%) were the three most common categories (any grade). The incidences of rare TRAEs with high risk of becoming serious, which occurred in < 1% of patients, were consistent with those in previous reports. The frequencies of TRAEs were not markedly increased in the specified patient groups relative to the overall population.ConclusionTo our knowledge, this is the largest study examining the safety of nivolumab-treated patients in real-world clinical practice including rare but potentially serious TRAEs. We found no new signals in the safety of nivolumab among the patient groups relative to the overall population, and no additional safety measures are required in these groups. Trial registration UMIN000048892 (overall analysis), JapicCTI-163272 (melanoma), Japic-163271 (non-small cell lung cancer), JapicCTI-184071 (head and neck cancer), JapicCTI-184070 (gastric cancer), and JapicCTI-184069 (renal cell cancer).

Dataset Information

Long-Term Safety and Efficacy of Sitagliptin for Type 2 Diabetes Mellitus in Japan: Results of a Multicentre, Open-Label, Observational Post-Marketing Surveillance Study.

Introduction

Methods

Results

Conclusion

Publications

Long-Term Safety and Efficacy of Sitagliptin for Type 2 Diabetes Mellitus in Japan: Results of a Multicentre, Open-Label, Observational Post-Marketing Surveillance Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets