Metformin does not prevent glucose intolerance but improves renal function and reduces oxidative stress in type 1 diabetes.

Master of Science in Pharmaceutical Sciences. University of KwaZulu-Natal, Durban 2016.Type 1 diabetes (T1D) is a chronic condition caused by the complete destruction of insulin producing pancreatic β-cells. Increased oxidative stress and impaired antioxidant capacity are associated with the development of diabetic complications such as diabetic nephropathy. Metformin, a drug commonly used in the treatment of type 2 diabetes, has been suggested to have antioxidant capacity. We hypothesise that metformin, when used as an adjunct to insulin in T1D may help prevent the development of diabetic nephropathy by decreasing oxidative stress. Sprague-Dawley rats (230-250g) were divided into 5 groups, (Group A: untreated controls, B: diabetic control, C: T1D + insulin (4U/kg twice daily), D: T1D + metformin (250mg/kg via oral gavage), E: T1D + metformin + insulin). Diabetes was induced in groups B-E by intraperitoneal streptozotocin injection at a dose of 65mg/kg body weight and diabetes was confirmed 48 hours later. Glucose tolerance test, serum and urinary electrolytes (K+,Cl- ,Na+), creatinine, urea, superoxide dismutase activity, glutathione concentration and malondialdehyde concentration were analysed. Metformin alone did not improve glucose intolerance. Both the diabetic control group as well as the group treated with metformin alone experienced hyperglycemia, polydipsia, polyuria, weight loss and impaired glucose tolerance. However, when metformin was added to insulin there was a significant increase in electrolyte excretion and also greatly improved creatinine clearance when compared to the diabetic control group. Metformin with insulin further reduced superoxide dismutase activity compared to the diabetic control, increased glutathione concentration as well as reduced malondialdehyde concentrations in both plasma and renal tissue. In conclusion, metformin has positive additive effects on oxidative stress and renal function when used as an adjunct therapy to insulin for T1D