Aims/hypothesis: Insulin glargine is a long-acting human insulin analogue often administered at bedtime to patients with type 2 diabetes. It reduces fasting blood glucose levels more efficiently and with less nocturnal hypoglycaemic events compared to human NPH insulin. Therefore, bedtime injections of insulin glargine and NPH insulin were compared overnight and in the morning.

Methods: In ten type 2 diabetic patients euglycaemic clamps were performed including [6,6']-²H₂ glucose to study the rate of disappearance (Rd) and endogeneous production (EGP) of glucose during the night. On separate days at bedtime (22:00), patients received a subcutaneous injection of insulin glargine, NPH insulin or saline in a randomized, double-blind fashion.

Results: Similar doses of both insulins had different metabolic profiles. NPH insulin had a greater effect on both Rd and EGP in the night compared to insulin glargine. By contrast, in the morning, insulin glargine was more effective increasing Rd by 5.8 (95% confidence interval 4.7 to 6.9) µmol kg^-1 min^-1 and by reducing EGP -5.7 (-5.0 to -6.4) compared to NPH insulin. Nearly 80% of glucose lowering effect in the morning was due to insulin glargine's reduction of EGP. Its injection was associated with one third lower morning glucagon levels compared to NPH insulin (p=0.021).

Conclusions/interpretation: Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycaemia and lower fasting glucose levels reported for insulin glargine compared to human NPH insulin.