SUB-CHRONIC EFFECT OF CO-ADMINISTRATION OF METHFORMINE AND AMILODIPINE ON SOME HAEMATOLOGICAL INDICES IN EXPERIMENTAL ANIMAL
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1.1 Background of the study
Metformin, which belongs to the biguanide class, is one of themost generally used oral hypoglycemic agents. It has been used formore than 50 years and was approved by the US Food and DrugAdministration (FDA) in 1994 (American Diabetes Association, 2009). Currently, many clinicalpractice guidelines for patients with type 2 diabetes, including theAmerican Diabetes Association (ADA), the European Associationfor the Study of Diabetes (EASD), and the Korean DiabetesAssociation (KDA), recommend that metformin treatment shouldbegin at the time of diagnosis of diabetes with lifestyle modificationin the absence of contraindications.Metformin is now the most widely used anti-diabetic drug, withalmost all guidelines throughout the world recommendingmetformin as first-line treatment for patients with type 2 diabetesmellitus (T2DM). Metformin may also be used to treat otherconditions involving insulin resistance, such as polycystic ovarysyndrome (PCOS) (Boyleet al., 2010). Metformin has beneficial effects oncarbohydrate metabolism, weight loss, and vascular protection but also has important side effects. For example, patients onlong-term metformin therapy were found to be at risk of anaemia (Maidaet al., 2011). This may be due to a metformin related vitamin B12reduction. It is reported that, 30% of patients receiving long-termmetformin treatment experienced malabsorption of vitamin B12,with a decrease in serum vitamin B12 concentration of 14% to30% (Burcelin, 2014).
Vitamin B12 is a vital nutrient for health. It plays an importantrole in the functioning of the brain and nervous system, and in theformation of red blood cells. In addition to anemia, vitamin B12deficiency may increase the severity of peripheral neuropathy inpatients with T2DM (Owenet al., 2000; Stephenne et al., 2011). Furthermore, because vitamin B12participates in the most important pathway of homocysteine (Hcy)metabolism, a reduction in vitamin B12 would increase plasmaconcentrations of Hcy, which is strongly linked to cardiovasculardisease in patients with T2DM and PCOS (Saeediet al., 2008).Although some clinical studies have reported that metforminlowered vitamin B12 level, other studies have reported that it didnot. To date, no consensus has been reached on whethermetformin induces vitamin B12 reduction. It is therefore imperative to know the effect of metformin on the hematological parameters of experimental animal (Wistar Rats) so as to arrive at a conclusion if the vitamin B12 deficiency is as a result of Diabetes mellitus or due to metformin (anti-diabetic drug) (Leoneet al., 2014).