Systematic review and meta-analysis of vildagliptin for treatment of type 2 diabetes

Abstract

This systematic review and meta-analysis provides an update on the efficacy and safety of vildagliptin for treatment of type 2 diabetes mellitus (T2DM). We searched MEDLINE, COCHRANE, EMBASE and the drug manufacturer's website for randomised controlled trials of vildagliptin in patients with T2DM. Sixty-nine studies (28,006 patients) were included in the meta-analysis. Compared with placebo vildagliptin reduced HbA1c (weighted mean difference WMD -0.69 %; 95 % CI -0.83 to -0.56 %; I (2) = 82 %), and it was as effective as other antidiabetic agents (WMD -0.01 %; 95 % CI -0.16 to 0.14 %; I (2) = 93 %), without increasing the risk for hypoglycemia (OR 0.83; 95 % CI 0.59 to 1.16; I (2) = 0 % vs. placebo, and OR 0.19; 95 % CI 0.15 to 0.24; I (2) = 78 % versus active comparators). However, it was associated with an increase in the incidence of arthralgia compared with other comparators (OR 1.23; 95 % CI 1.02 to 1.48; I (2) = 0 %). On the contrary, vildagliptin did not increase the incidence of pancreatitis (OR 0.97; 95 % CI 0.37 to 2.53; I (2) = 0 %), serious adverse events (OR 0.98; 95 % CI 0.88 to 1.09; I (2) = 0 %) or death (OR 1.10, 95 % CI 0.75 to 1.61; I (2) = 0 %). Finally, odds ratio (OR) for heart failure, and overall cardiovascular and cerebrovascular events was 0.77 (95 % CI 0.46 to 1.30; I (2) = 0 %) and 0.91 (95 % CI 0.73 to 1.14; I (2) = 0 %), respectively. Vildagliptin is an effective and safe therapeutic option for patients with T2DM, both as monotherapy and as add-on treatment.

Pancreatic safety of vildagliptin in patients with type 2 diabetes mellitus: A European, noninterventional, postauthorization safety study

“…Our data are in line with the results from a meta‐analysis of randomized studies for vildagliptin, a meta‐analysis for DPP‐4 inhibitors based on observational data only or of both, observational and RCTs and various noninterventional studies which reported no increased risk of acute pancreatitis compared to DPP‐4 inhibitor nonusers. In contrast, a recent noninterventional study and a meta‐analysis of three large randomized DPP‐4 inhibitor outcome trials (none of which included vildagliptin) reported an increased risk of pancreatitis.…”

Association between vildagliptin and risk of angioedema, foot ulcers, skin lesions, hepatic toxicity, and serious infections in patients with type 2 diabetes mellitus: A European multidatabase, noninterventional, postauthorization safety study

“…15 Furthermore, a recent meta-analysis of 69 RCTs revealed no association of vildagliptin with elevated hepatic enzymes (OR = 0.61; 95% CI: 0.28-1.36). 18 Similarly, no indication of an increased risk of serious infections was observed with vildagliptin. Safety data from a meta-analysis reported that the incidence of infections was comparable between vildagliptin and comparator groups.…”

“…This is in line with a pooled analysis of 38 RCTs which also showed no evidence of an increased risk for ALT/AST ≥ 3 × ULN accompanied by bilirubin for vildagliptin 50 mg bid relative to comparators (OR = 1.19; 95% CI: 0.29‐4.90; P = 0.999) . Furthermore, a recent meta‐analysis of 69 RCTs revealed no association of vildagliptin with elevated hepatic enzymes (OR = 0.61; 95% CI: 0.28‐1.36) …”

Vildagliptin-induced acute pancreatitis without enzyme elevation

“…However, improvement of abdominal pain and abdominal imaging despite continuation of medications except vildagliptin supports that vildagliptin is the only possible culprit in the development of AP. DPP-4 inhibitors are important drugs for the treatment of DM2, and they are generally considered safe and well tolerated (7). An AP risk has been previously noted with this class of medications, especially with sitagliptin.…”

“…Although DPP-4 inhibitors are generally considered safe, there were reports of severe pancreatitis in patients receiving sitagliptin, a DPP-4 inhibitor, which prompted the Food and Drug Administration (FDA) to issue an alert on this adverse reaction (6). A meta-analysis did not reveal an increased incidence of pancreatitis with the newer DPP-4 inhibitor, vildagliptin (7). However, there are recent reports of AP due to vildagliptin (8,9).…”