Adding insulin glargine vs. NPH insulin to metformin results in a more efficient postprandial β-cell protection in individuals with type 2 diabetes

AIM Postprandial release of intact proinsulin (IP) is an independent marker for beta-cell dysfunction in patients with type 2 diabetes. This open-label, parallel-group, two-arm, pilot study compared the beta-cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin. MATERIAL AND METHODS Overall, 28 insulin-naive type 2 diabetes subjects (mean +/- SD age, 61.5 +/- 6.7 years; diabetes duration, 9.8 +/- 6.5 years; HbA1c, 7.1 +/- 0.5%; BMI, 30.7 +/- 4.3 kg/m(2)) treated with metformin and sulfonylurea were randomized to add once-daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre- and postprandial blood sampling to measure plasma IP, total insulin and blood glucose (BG). RESULTS Insulin dose after 3 months was comparable in both groups (GLA vs. NPH: 23.6 +/- 13.4 vs. 23.3 +/- 12.7; p = NS ). Both treatments significantly reduced fasting BG levels (GLA: 158 +/- 19 to 121 +/- 23 mg/dl; NPH: 156 +/- 34 to 119 +/- 29 mg/dl; both p < 0.01 vs. baseline). Fasting and postprandial BG levels did not differ between groups. IP levels decreased in both groups (p < 0.05 at all timepoints). Although IP release after breakfast did not differ between treatments, GLA induced a greater reduction in IP release after lunch (p = 0.08) and dinner (p = 0.04). Total plasma insulin levels did not differ between groups. CONCLUSIONS Adding basal insulin to metformin reduces postprandial beta-cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces beta-cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.