عنوان الدراسة
لمحة الأعراض الجانبية الضارة لمثبطات الأنزيم ببتايديز الثنائي-4 (ستاجلبتين وسكساجلبتين وفلداجلبتين وليناجلبتين): التنقيب عن البيانات للنسخة المعلنة لنظام الإبلاغ عن الأعراض الجانبية الضائرة التابع لإدارة الغذاء والدواء الأمريكية.
الخلفية
داء السكري النمط 2 (T2DM) هو الشكل الأكثر شيوعا لمرض السكري. الأدوية الفموية هي الدعامة الأساسية للعلاج الدوائي لـهذا المرض . تُعد مثبطات الإنزيم الأنزيم ببتايديز الثنائي-4 ومنها ستاجلبتين وسكساجلبتين وفلداجلبتين وليناجلبتين إضافة جديدة لطرق العلاج المضادة لمرض السكر وقد تم استخدامها على نطاق واسع وغير مقنن وعشاوائي. لهذه الأدوية هياكل كيميائية مختلفة بشكل كبير الأمر الذي يؤدي إلى اختلافات في خصائصها الحركية الدوائية والدوائية. ليس من الواضح تماما ما إذا كانت هذه الاختلافات قد تؤدي إلى اختلاف الأعراض الجانبية الضارة التي تسببها . اضافة الى ذلك قد تختلف سمات سلامة الأدوية في الممارسة السريرية عن التجارب السريرية المصممة جيدا. لذلك من الضروري استكشاف الأعراض السلبية التي تسببهامثبطات الإنزيم الأنزيم ببتايديز الثنائي-4 في بيئة العالم الحقيقي.تهدف أنظمة الإبلاغ العفويعن الأعراض الجانبيةقواعد بيانات كبيرة للتيقظ الدوائي والتي يمكن استخدامها في تقييمات السلامة بشأن استخدام الأدوية في الممارسة السريرية. تم إنشاء نظام الإبلاغ عن الأحداث الضائرة وهو قاعدة بيانات مفتوحة للمعلومات لخدمة برامج مراقبة ما بعد التسويق الخاصة بإدارة الغذاء والدواء الأمريكية للأدوية والمنتجات العلاجية. يتم تقييم التقارير العفويةعن الأعراض الجانبيةمن خلال خوارزميات الكشف عن الإشارات الكمية حيث تكون الإشارة مؤشرا لقضايا السلامة الحقيقية المحتملة. يعد الكشف عن الإشارات أحد الأدوات الأساسية للتيقظ الدوائي . كشفت دراسات التيقظ الدوائي السابقة عن الارتباط بين أدوية مثبطات الإنزيم الأنزيم ببتايديز الثنائي-4 وبعض الأحداث الضائرة الخاصة.
Background
Type 2 diabetes mellitus (T2DM) is the most common form of diabetes. Oral agents are the mainstay of pharmacological treatment for T2DM. Dipeptidyl peptidase-4 inhibitors (DPP-4is) are a valuable addition to the antidiabetic treatment modalities and have been widely used [1]. DPP-4is, sitagliptin, saxagliptin, linagliptin, vildagliptin, and alogliptin, have significantly different chemical structures, leading to differences in their pharmacokinetic and pharmacodynamic properties. It is not entirely clear if these differences may result in differing safety profiles [2]. The drugs’ safety profiles in clinical practice may differ from clinical trials that have been well-designed [3]. Therefore, it is necessary to explore adverse events (AEs) induced by DPP-4is in a real-world environment.
Spontaneous reporting systems (SRS) of AEs generate large pharmacovigilance databases, which can be used for safety assessments on drug utilization in clinical practice [4]. The FDA Adverse Event Reporting System (FAERS), an open information database, was established to serve the FDA’s post-marketing monitoring programs for drugs and therapeutic products. The AE reports are evaluated through quantitative signal detection algorithms, where a signal is an indicator of possible real safety issues [5]. Signal detection is one of the essential tools of pharmacovigilance [6].
Previous pharmacovigilance studies have revealed the association between DPP-4is and some particular adverse events [7–9]. To achieve the latest information about the safety profiles of DPP-4is, we queried an international SRS, namely FAERS, to characterize the reporting pattern of DPP-4is and map the entire spectrum of AEs by the pharmacovigilance approach.
الاستنتاجات
تمت مراجعة ملفات لمحة الأمان الخاصة بأدوية مثبطات الأنزيم ببتايديز الثنائي-4 ومنها ستاجلبتين (الجانوفيا) وسكساجلبتين (أونكلايزا) وفلداجلبتين (كالفص) وليناجلبتين (نسينا)
( sitagliptin , saxagliptin , linagliptin , vildagliptin) باستخدام نظام الإبلاغ عن الأعراض الجانبية المقدم لإدارة الغذاء والدواء الأمريكية
(FDA Adverse Event Reporting System) ومن بين أدوية السكري الأخرى من غير الأنسولين ، وقد لوحظ ارتباط مثبطات الأنزيم ببتايديز الثنائي-4 بزيادة ملحوظة في الإبلاغ عن الأعراض الجانبية المتعلقة بالجهاز الهضمي والتهاب البنكرياس والأورام الخبيثة والإلتهابات والجهاز العضلي الهيكلي والاضطرابات العامة وفرط الحساسية والجلد ، مما يدعم أدلة التجارب السريرية. علاوة على ذلك ، لم يتم الكشف عن إشارة لاعتلال القلب والكسور. النتائج التي توصلت إليها هذه الدراسة تحتاج إلى مزيد من التحقق من الصحة ويجب تفسيرها بحذر ، بالنظر إلى قيود التيقظ الدوائي. ومع ذلك ، بالنسبة للأطباء ، يجب أن يكونوا على دراية بهذه الارتباطات المحتملة ، ويجب أن يؤخذ في الاعتبار الأمراض المصاحبة للمريض وتاريخها والآثار الضارة المحتملة لهذه الأدوية. تحتاج الأبحاث المستقبلية إلى التركيز على مخاوف السلامة وخاصة تطور السرطان والتهاب البنكرياس. أخيرا توفر هذه الدراسة فهماً أفضل لموضوع سلامة هذه الأدوية وأهمية الإلتزام بمبدأ التيقظ الدوائي.
Conclusions
The safety profiles of sitagliptin, saxagliptin, linagliptin, and vildagliptin were reviewed using Adverse Event Reporting System AERs submitted to the FAERS FDA Adverse Event Reporting System (FAERS). Among non-insulin antidiabetics, DPP-4is are associated with higher AEs reporting of the gastrointestinal tract, pancreatitis, malignancies, infection, musculoskeletal system, general disorders, hypersensitivity and skin, corroborating clinical trial evidence. Furthermore, a signal is not detected for cardiopathy and fracture. Our findings need further validation and should be interpreted with caution, given the limitations of the pharmacovigilance. However, for physicians, these possible associations should be aware, and the patient’s comorbidities and history and potential adverse effects of the medicine must be taken into consideration. Future research needs to focus on safety concerns, especially the development of cancer and pancreatitis. Finally, our study provides a better understanding of the safety profiles of DPP-4i in a pharmacovigilance way.
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