Geçen hafta FDA tarafından pankreatit ve kanser yapıcı yan etkileri yönünden incelemeye alınan bazı diyabet ilaçları EMEA (Avrupa İlaç Kurumu) tarafından da incemeye alındı. Yetkililer kısa sürede araştırma sonuçlarının açıklanacağını bildirmekte.
Bağımsız araştırmacılar tarafından yapılan çalışmada bazı diyabet ilaçlarının pankreatit ve pankreas kanseri yapmaları yönünden incelenmeye alındı (Byetta, Bydureon), liraglutide (Victoza), lixisenatide (Lyxumia), sitagliptin (Efficib, Januvia, Janumet, Ristaben, Ristfor, Tesavel, Velmetia, Xelevia), saxagliptin (Komboglyze, Onglyza), linagliptin (Jentadueto, Trajenta) and vildagliptin (Eucreas, Galvus, Icandra, Jalra, Xiliarx, Zomarist). Yapılan araştırmada (özeti aşağıda verilmiştir) bu ilaçları ( incretin mimemtic ilaçlar) kullananlarda kanser riskinin kullanmayanlar nazaran anlamlı olarak fazla olduğunu göstermiştir.
European Medicines Agency investigates findings on pancreatic risks with GLP-1-based therapies for type-2 diabetes
The European Medicines Agency is investigating findings by a group of independent academic researchers that suggest an increased risk of pancreatitis (inflammation of the pancreas) and precancerous cellular changes called pancreatic-duct metaplasia in patients with type-2 diabetes treated with so-called GLP-1-based therapies (glucagon-like-peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors).
GLP-1-based therapies are also known as incretin mimetics. In the EU they include exenatide(Byetta, Bydureon), liraglutide (Victoza), lixisenatide (Lyxumia), sitagliptin (Efficib, Januvia, Janumet, Ristaben, Ristfor, Tesavel, Velmetia, Xelevia), saxagliptin (Komboglyze, Onglyza), linagliptin (Jentadueto, Trajenta) and vildagliptin (Eucreas, Galvus, Icandra, Jalra, Xiliarx, Zomarist). These medicines act like hormones called incretins (hormones produced in the intestine) by increasing the amount of insulin released by the pancreas in response to food. They are authorised for use together with diet and exercise in patients with type-2 diabetes.
Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with increased Exocrine Pancreas Dysplasia and the potential for Glucagon-producing Neuroendocrine Tumors
. Alexandra E Butler1, Martha Campbell-Thompson2, Tatyana Gurlo1, David W Dawson3, Mark Atkinson2 and Peter C Butler1+
. 1Department of Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California
. 2College of Medicine, Departments of Pathology and Pediatrics, University of Florida, Gainesville, Florida 32610-0275.
. 3Department of Pathology and Laboratory Medicine, University of California Los Angeles, David Geffen School of Medicine, Los Angeles, California
Abstract
Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic β cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age matched organ donors with type 2 diabetes (DM) treated by incretin therapy (n=8) or other therapy (n=12) and non diabetic controls (n=14) reveals a ∼40% increased pancreatic mass in DM treated with incretin therapy with both increased exocrine cell proliferation (p<0.0001) and dysplasia (increased pancreatic intraepithelia neoplasia, p<0.01). Pancreas in DM treated with incretin therapy was notable for α cell hyperplasia and glucagon expressing microadenomas (3/8) and a neuroendocrine tumor. β cell mass was reduced by approximately 60% in those with DM, yet a 6 fold increase was observed in incretin treated subjects although diabetes persists. Endocrine cells co-staining for insulin and glucagon were increased in DM compared to non diabetic controls (p<0.05) and markedly further increased by incretin therapy (p<0.05). In conclusion, in humans, incretin therapy resulted in a marked expansion of the exocrine and endocrine pancreatic compartments, the former being accompanied by increased proliferation and dysplasia, the latter by α cell hyperplasia with the potential for evolution into neuroendocrine tumors.