Oral combination therapy: repaglinide plus metformin for treatment of type 2 diabetes

Abstract

Type 2 diabetes is characterized by decreases in insulin secretion and insulin sensitivity. Several classes of oral antidiabetic medications are currently approved for the treatment of type 2 diabetes. A stepwise treatment approach from monotherapy to combination therapy is traditionally used; however, the frequency of treatment failure with monotherapy has resulted in a move towards earlier treatment with combination therapies that target the two principal defects in glycaemic control. One such combination regimen is repaglinide (a prandial glucose regulator that increases insulin release) plus metformin (an insulin sensitizer that inhibits hepatic glucose output, increases peripheral glucose uptake and utilization and minimizes weight gain). Findings from several clinical trials have shown that combination therapy with repaglinide plus metformin is well tolerated and results in greater reductions of haemoglobin A(1c) and fasting plasma glucose values compared with either monotherapy. Repaglinide may also provide a more suitable alternative to combination therapy with sulphonylureas and metformin because of its reduced propensity for hypoglycaemia. The combination regimen of repaglinide plus metformin should therefore be considered as a valuable option in the management of patients with type 2 diabetes when monotherapy is no longer adequate.

State of the art paper The role of nateglinide and repaglinide, derivatives of meglitinide, in the treatment of type 2 diabetes mellitus

“…No severe hypoglycemic episodes occurred in patients treated with repaglinide plus metformin in a randomized study in naive T2DM patients, and combination therapy with repaglinide plus metformin resulted in fewer hypoglycemias than combination therapy with sulfonylureas [ 63 , 64 ]. Repaglinide caused fewer hypoglycemias than glibenclamide also in elderly patients, as demonstrated by a small randomized crossover study in elderly patients [ 65 ].…”

Oral Hypoglycaemic Agents in the Management of Type Ii Diabetes Mellitus

“…61 Repaglinide, first clinically available insulin secretagogue, specifically enhances early-phase prandial insulin response by increasing the sensitivity of β-cells to elevated glucose levels, producing a greater insulin release under hyperglycaemic conditions. 62,63 In vitro, Repaglinide increases insulin release from β-cells only in the presence of glucose (As seen in the presence of 5 and 10 mmol/L of glucose), thus carries low risk of hypoglycaemia, whereas glibenclamide stimulates insulin secretion in the absence of glucose. 64 hence greater risk of hypoglycaemia.…”

Recomendaciones para el tratamiento farmacológico de la hiperglucemia en la diabetes tipo 2

“…Las glinidas constituyen una buena alternativa a las sulfonilureas en pacientes con inges-tas más irregulares por su corto periodo de acción, así como en pacientes alérgicos a sulfamidas o, en el caso de la repaglinida, en pacientes que presenten insuficiencia renal moderada 52 . En cuanto al riesgo de hipoglucemia e incremento de peso, pueden considerarse superponibles, con una potencia inferior a la de nateglinida 53 y bastante similar a la de repaglinida 54 . • Inhibidores de la DPP-4.…”