Reprotoxic activities of vildagliptin administration in male Wistar rats

Vildagliptin is an oral hypoglycemic agent used in the management of diabetes. Some oral antidiabetic drugs have been implicated in reproductive toxicity.The objective of this study was to investigate the effects of daily administration of vildagliptin at different dosages (0.35 mg/kg B.W., 0.70 mg/kg B.W. and 1.40 mg/kg B.W.) to male Wistar rats for 8 weeks. Sperm parameters, serum concentrations of testosterone, follicle stimulating hormone and luteinizing hormone and the histology of the testis of the rats were assessed. Another set of rats were also treated for 8 weeks and allowed to recover and the same parameters were assessed in them. Fertility study was conducted by determining their litter size. The results showed that vildagliptin administration significantly reduced sperm count and motility of the treated rats. It also significantly increased the number of abnormal sperms. Serum level of testosterone was significantly decreased while luteinizing hormone and follicle stimulating hormone levels showed no significant change. The histoarchitecture of the testis of the treated rats appeared visibly normal. The litter size was also significantly reduced. Most of the changes observed were dose dependent. However, these parameters were restored towards normal in the recovery group. Our results suggest that vildagliptin adversely affected sperm parameters, affected litter size and disrupted the pituitary - gonadal axis. These changes were however reversed upon cessation of drug administration.

Short-term renal and metabolic effects of low dose vildagliptin treatment added-on insulin therapy in non-proteinuric patients with type 2 diabetes: open-label randomized prospective study

ABSTRACT Objective The aim of this randomized comparative study was to assess renal and metabolic effects of vildagliptin in insulin-treated type 2 diabetes (T2DM) patients without overt chronic kidney disease. Subjects and methods We randomized 47 insulin-treated non-proteinuric patients with satisfactory controlled T2DM and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m 2 either to continue insulin therapy (control) or to receive combined insulin-vildagliptin treatment (VIG group). We assessed eGFR using serum creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys), and urinary creatinine-adjusted excretion of albumin (UACR), type IV collagen (uCol IV/Cr), and neutrophil gelatinase-associated lipocalin (uNGAL/Cr) at baseline and after 6 months of treatment. Results Study groups were comparable in terms of age and sex (60.1 ± 6.1 years and 42.9% men in control group vs. 60.8 ± 5.2 years and 39.1% in VIG group). After 6 months of treatment, there were no significant changes in main assessed parameters in control group. VIG group demonstrated significant decrease in HbA1c, diastolic blood pressure, frequency of hypoglycemia, and high-sensitivity C-reactive protein level as compared to the changes in control group. While eGFRcreat, UACR, and uNGAL/Cr showed no significant changes after vildagliptin addition, eGFRcys, eGFRcreat-cys, and uCol IV/Cr changed significantly in comparison with control group (+7.0% [3.7;13.3]; +5.1% [1.4;8.5]; -32,8% [-55.8;-24.4], respectively, p < 0.01 each). Correlation and regression analysis revealed glucose-independent pattern of these changes. Conclusion Addition of vildagliptin to ongoing insulin therapy in patients with T2DM was associated with a reduction in uCol IV/Cr and an increase in eGFRcys and eGFRcreat-cys, independent of T2DM control parameters.

Effectiveness, safety and tolerability of vildagliptin and vildagliptin+metformin in real-world setting in the Philippines--Results from the GUARD study

INTRODUCTION: GUARD (vildaGliptin clinical Use in reAl woRlD) was  a  multinational,  prospective,  observational  study that assessed the effectiveness,safety  and  tolerability of vildagliptin and vildagliptin+metformin in patients with type 2 diabetes mellitus (T2DM) under real-world conditions across four  geographical  regions  (Asia,  the  Middle  East,  Central  America and Africa). The current paper discusses the results of patients with T2DM enrolled in the Philippines.METHODS: Patients  with  T2DM  who  were  prescribed vildagliptin or vildagliptin+metformin combination therapy were enrolled and followed as per routine clinical practice for 24 ± six weeks. Primary endpoint was the change in HbA1c from  baseline  to  study  end  (week  24±6).  Key  secondary endpoints included proportion of patients reaching target HbA1c ?7.0%, incidence of hypoglycemic events, adverse events (AEs) and serious AEs (SAEs).RESULTS: A total of 1,117 patients were included in the final analysis, 280 on vildagliptin (of these, eight patients received additional oral antidiabetes medications) and 837 on vildagliptin+metformin. At baseline, the mean (±SD) age of the enrolled population was 54.1±11.5 years, BMI 26.3±4.7 kg/m2, HbA1c 8.0±1.2% and T2DM duration 2.3±4.0 years.At  study  end,  significant  mean  (±SE)  reductions  in  HbA1c of -1.2±0.1% (pCONCLUSION: Vildagliptin  and  vildagliptin+metformin significantly  reduced  HbA1c  with  good  weight  control and low incidence of hypoglycemia in patients with T2DM under real-world conditions in Philippines