Background: Oxidative stress and impaired antioxidant capacity in diabetes are associated
with diabetic nephropathy. Metformin, as an adjunct to insulin could decrease oxidative
stress and may therefore improve renal function in type 1 diabetes (T1D).
Objectives: To investigate the effects of metformin as adds-on therapy to insulin on renal
dysfunction in T1D.
Materials and Methods: Male Sprague-Dawley rats (230-250 g) were divided into 5 groups
(n =7). Rats in groups A and B were orally treated with 3.0 mL/kg body weight (BW) of
distilled water, while those in groups C and D were treated with insulin (4.0 U/kg BW
bid) or oral metformin (250 mg/kg BW), respectively. Group E rats were similarly treated
with both metformin and insulin. Groups B-E were rendered diabetic by intraperitoneal
injections of 65 mg/kg BW of streptozotocin. Fasting blood glucose concentrations and
glucose tolerance tests were done. The animals were sacrificed by halothane overdose
after 56 days, blood taken by cardiac puncture and kidneys excised and stored at -80°C for
Results: Untreated diabetic rats exhibited significant weight loss, increased polydipsia and
polyuria, impaired glucose tolerance, electrolyte retention, reduced creatinine clearance
and urea excretion and increased oxidative stress compared to controls, respectively.
However, these were reversed by treatment with metformin and insulin.
Conclusions: Metformin does not improve glycemic control in TID but exerts renoprotective
effects by reducing oxidative stress in the presence of insulin. Metformin should therefore
be considered for adjunct therapy with insulin in TID.