Long-term Effects of Mitiglinide in Japanese Diabetics Inadequately Controlled with DPP-4 Inhibitor or Biguanide Monotherapy

Abstract

IntroductionThe goal of treatment in diabetes is to control hyperglycemia to near-normal glucose levels, which is important to prevent the progression of microvascular and macrovascular complications. Mitiglinide is a rapid- and short-acting insulinotropic sulfonylurea receptor ligand that is known to improve postprandial hyperglycemia in patients with type 2 diabetes. The aim of this study was to investigate the long-term efficacy and safety of mitiglinide in Japanese type 2 diabetic patients inadequately controlled by dipeptidyl peptidase-4 (DPP-4) inhibitor or biguanide monotherapy.MethodsIn patients with type 2 diabetes mellitus (T2DM) receiving a stable monotherapy regimen with a DPP-4 inhibitor or biguanide added to dietary therapy, an additional 10 mg mitiglinide was administered for 52 weeks. The efficacy end points were postprandial plasma glucose (PPG) (30 min, 1 h, 2 h), postprandial insulin (30 min, 1 h, 2 h), insulinogenic index, 1,5-anhydroglucitol (1,5-AG), glycated hemoglobin (HbA1c), and fasting plasma glucose. The safety end points included the incidence and types of adverse events and adverse drug reactions.ResultsA total of 136 patients with T2DM were eligible for enrollment in this study and received mitiglinide. The average HbA1c before the start of mitiglinide administration (baseline) was 7.47% in the DPP-4 inhibitor combined treatment group (DPP-4 inhibitor CTG) and 7.50% in the biguanide combined treatment group (biguanide CTG), and the 2 h PPG was 248.1 and 243.3 mg/dL, respectively. Following the addition of mitiglinide to the treatment regimen for 52 weeks, the early postprandial decrease in insulin secretion improved and PPG improved in both the DPP-4 inhibitor CTG and biguanide CTG. At final evaluation, the HbA1c <7.0% achievement rate was 57.4% in the DPP-4 inhibitor CTG and 29.2% in the biguanide CTG. The incidence of hypoglycemia in the DPP-4 inhibitor CTG and biguanide CTG was 3.0% (2/67 patients) and 2.9% (2/69 patients), respectively. The hypoglycemic symptoms were mild in all cases.ConclusionCombination therapy with mitiglinide and DPP-4 inhibitors or biguanides improved glycemic control over the long term without increasing risks to safety due to events such as hypoglycemia, and this is a clinically promising therapeutic strategy in T2DM.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0051-5) contains supplementary material, which is available to authorized users.