Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis
Open Access
- 14 April 2010
- journal article
- review article
- Published by Hindawi Limited in International Journal of Clinical Practice
- Vol. 64 (7), 984-990
- https://doi.org/10.1111/j.1742-1241.2010.02382.x
Abstract
Recent case reports of acute pancreatitis in patients with type 2 diabetes (T2DM) treated with incretin-based therapies have triggered interest regarding the possibility of a mechanism-based association between pancreatitis and glucagon-like peptide-1 mimetics or dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review was to describe the controlled preclinical and clinical trial data regarding the incidence of pancreatitis with sitagliptin, the first DPP-4 inhibitor approved for use in patients with T2DM. Tissue samples from multiple animal species treated with sitagliptin for up to 2 years at plasma exposures substantially in excess of human exposure were evaluated to determine whether any potential gross or histomorphological changes suggestive of pancreatitis occurred. Sections were prepared by routine methods, stained with haematoxylin and eosin and examined microscopically. A pooled analysis of 19 controlled clinical trials, comprising 10,246 patients with T2DM treated for up to 2 years, was performed using patient-level data from each study for the evaluation of clinical and laboratory adverse events. Adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 system. Incidences of adverse events were adjusted for patient exposure. Tissue samples from preclinical studies in multiple animal species did not reveal any evidence of treatment-related pancreatitis. The pooled analysis of controlled clinical trials revealed similar incidence rates of pancreatitis in patients treated with sitagliptin compared with those not treated with sitagliptin (0.08 events per 100 patient-years vs. 0.10 events per 100 patient-years, respectively). Preclinical and clinical trial data with sitagliptin to date do not indicate an increased risk of pancreatitis in patients with T2DM treated with sitagliptin.Keywords
This publication has 36 references indexed in Scilit:
- Glucagon-Like Peptide-1 Receptor Activation Modulates Pancreatitis-Associated Gene Expression But Does Not Modify the Susceptibility to Experimental Pancreatitis in MiceDiabetes, 2009
- Beneficial Endocrine but Adverse Exocrine Effects of Sitagliptin in the Human Islet Amyloid Polypeptide Transgenic Rat Model of Type 2 DiabetesDiabetes, 2009
- Increased Risk of Acute Pancreatitis and Biliary Disease Observed in Patients With Type 2 DiabetesDiabetes Care, 2009
- Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysisBMC Endocrine Disorders, 2008
- Incretin Receptors for Glucagon-Like Peptide 1 and Glucose-Dependent Insulinotropic Polypeptide Are Essential for the Sustained Metabolic Actions of Vildagliptin in MiceDiabetes, 2007
- Dipeptidyl Peptidase-4 Inhibition and the Treatment of Type 2 DiabetesDiabetes Care, 2007
- AGA Institute Technical Review on Acute PancreatitisGastroenterology, 2007
- Exenatide: An incretin mimetic for the treatment of type 2 diabetes mellitusClinical Therapeutics, 2006
- Metformin-Induced Pancreatitis: A possible adverse drug effect during acute renal failureDiabetes Care, 2006
- Metformin induced acute pancreatitis precipitated by renal failurePublished by Oxford University Press (OUP) ,2004