In this 24-week study of 515 patients with T2DM and moderate or severe RI, vildagliptin added to ongoing antidiabetic therapy had a safety profile similar to placebo. Further, relative to placebo, vildagliptin elicited a statistically and clinically significant decrease in A1C in patients with moderate or severe RI.

Aim:To assess the safety of vildagliptin versus all comparators (ACs) with regard to organs, systems or tissues of particular interest in type 2 diabetes (T2DM) and areas of potential concern with dipeptidyl peptidase-IV (DPP-4) inhibitors.Methods: Data were pooled from 38 studies where vildagliptin was given for ≥12 to >104 weeks in patients with T2DM. Absolute and exposure-adjusted incidence rates and Peto odds ratios (ORs) versus ACs with corresponding 95% confidence intervals (CI) were calculated.Results: There were >7000 subject-years of exposure (SYE) to vildagliptin 50 mg bid and >6500 SYE to ACs. For mild hepatic enzyme elevations with and without elevated bilirubin levels, the ORs for vildagliptin 50 mg bid were 1.24 (95% CI : Conclusions:The present meta-analyses indicate that vildagliptin was not associated with increased risk of hepatic events or hepatic enzyme elevations indicative of drug-induced liver injury, pancreatitis, infections or skin-related toxicity. Keywords: dipeptidyl peptidase-4, drug-induced liver injury, infections, pancreatitis, renal impairment, skin IntroductionThe safety of any new therapeutic entity is of great importance, particularly if it is indicated for a chronic and progressive disease such as type 2 diabetes mellitus (T2DM), that requires lifelong treatment. In the case of T2DM, the nature of the disorder itself imposes an increased risk for several organ-specific complications that could be exacerbated by drug treatment. These include drug-induced liver injury (DILI) resulting from high background rate of non-alcoholic fatty liver disease (NAFLD) [1,2] and the association with hepatitis C infection [3,4], pancreatitis [5,6], and a broad spectrum of cardiovascular disease [7,8]. T2DM is also a major risk factor for chronic kidney disease. It was therefore of interest to examine the overall safety of vildagliptin in patients with renal impairment, although at present there is no evidence of a doserelated increase in adverse events (AEs; comparing vildagliptin Correspondence to: Monica Ligueros-Saylan, MD, Novartis Pharmaceuticals Corporation, 180 Park Avenue, Bldg 105 2W132. Florham Park, NJ07932, USA E-mail: monica.ligueros@novartis.com 50 mg qd to 50 mg bid), and the major pathway for vildagliptin elimination is metabolism (i.e. hydrolysis) [9].In addition to the aforementioned areas of potential safety concern related to any and all antidiabetic treatments, some specific classes of drugs are associated with additional possible adverse experiences. For the dipeptidyl peptidase-IV (DPP-4) inhibitors, concern has been raised about potential effects on the immune system [10,11]. This concern arises from the fact that the DPP-4 enzyme, also known as the protein CD26, is expressed on activated T cells [12], and sitagliptin treatment was reported to significantly increase the incidence of nasopharyngitis [13]. However, the proteolytic activity of DPP-4/CD26 is not thought to be involved in its role in immune function [14], and DPP-4/CD26 knockout mice appear to be healthy...

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