Aim: Postprandial release of intact proinsulin (IP) is an independent marker for β‐cell dysfunction in patients with type 2 diabetes. This open‐label, parallel‐group, two‐arm, pilot study compared the β‐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/m2) 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 β‐cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces β‐cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.