Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naive elderly patients with type 2 diabetes

Aim: The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM). Methods: Study 1 was a 12-week, multicentre, randomized, double blind and placebo-controlled study of nateglinide monotherapy (120 mg, before meals) in 66 drug-naive patients with T2DM aged >= 65 years. Study 2 was a 104-week, multicentre, randomized, double blind and active-controlled study of nateglinide (120 mg, before meals) or glyburide (up to 5 mg bid) in combination with metformin (up to 1000 mg bid) in 69 treatment-naive patients with T2DM aged >= 65 years. HbA(1c), fasting and postprandial glucose levels, and safety assessments were made. Results: In Study 1, nateglinide significantly reduced HbA(1c) from baseline (7.6 +/- 0.1% to 6.9 +/- 0.1%; Delta = -0.7 +/- 0.1%, p < 0.001) and compared with placebo (between-group difference = -0.5%, p = 0.004 vs. nateglinide). No hypoglycaemia was reported. In Study 2, combination therapy with nateglinide/metformin significantly reduced HbA(1c) from baseline (7.8 +/- 0.2% to 6.6 +/- 0.1%; Delta = -1.2 +/- 0.2%, p < 0.001), as did glyburide/metformin (7.7 +/- 0.1% to 6.5 +/- 0.1%; Delta = -1.2 +/- 0.1%, p < 0.001). There was no difference between treatments (p = 0.310). One nateglinide/metformin-treated patient experienced a mild hypoglycaemic episode compared with eight episodes in eight patients on glyburide/metformin; one severe episode led to discontinuation. Target HbA(1c) (< 7.0%) was achieved by 60% of patients receiving nateglinide (Study 1) and 70% of nateglinide/metformin-treated patients (Study 2). Conclusions: Initial drug treatment with nateglinide, alone or in combination with metformin, is well tolerated and produces clinically meaningful improvements in glycaemic control in elderly patients with T2DM.