Endocrine Abstracts

Background: Presently, a great deal of attention is being paid to investigation of pleiotropic effects of oral antidiabetic drugs. Several recent animal studies have suggested that vildagliptin and metformin could play some positive role in preventing the evolvement of diabetic nephropathy.

Aim: This pilot study, concerned with high-fat fed heminephrectomized streptozotocin (STZ)-induced diabetic rats, aimed to evaluate and compare the effects of metformin, vildagliptin and their combination on kidney histopathology and routine renal function markers.

Methods: Three weeks following unilateral nephrectomy male Wistar rats were fed with either a normal diet (non-diabetic (ND) rats) or high-fat diet for 5 weeks. Diabetes in high-fat fed rats was induced by two-time intraperitoneal administration of STZ (30 mg/kg). 9 weeks later, rats in diabetic group were divided into three subgroups to receive metformin (300 mg/kg per day in drinking water (M)), vildagliptin (8 mg/kg per day in drinking water (V)), half-dose combination (vildagliptin 4 mg/kg per day + metformin 150 mg/kg perday (V+M)), or placebo (P) for another 8 weeks, n=5 each.

Results: Glycated haemoglobin (%) didn’t differ between diabetic treated groups (M=11.1±0.28, V=10.7±0.26, V+M=10.7±0.28, P≥0.05 each; P=12.8±0.35, P<0.05 each),and was markedly higher compared with ND (4.7±0.15, P<0.01 each). Although all antihyperglycaemic compounds ameliorated serum creatinine (umol/l) level (M=93.8±6.7, V=84.7±2.9, V+M=79.4±5.8; P=103.1±3.7, P<0.05 each), however, only vildagliptin monotherapy and combined treatment were able to considerably improve creatinine clearance (V=2.69±0.16 ml/min/kg; V+M=3.4±0.18; P=1.7±0.11, P<0.05 each), and reduce urinary albumin excretion ratio (V=10.5±1.07 mg/24 h, V+M=6.7±0.47; P=26.9±2.0, P<0.01 each). Moreover, nephroprotection in V and V+M groups was also associated with restoring morphological changes in kidney tissue.

Conclusion: We determined that vildagliptin alone, and in half-dose combination with metformin might attenuate diabetic nephropathy, in addition to hypoglycemic action. Furthermore, half-dose combined V+M treatment was more effective for this prevention.