Pharmacokinetics and pharmacodynamics of insulin glargine–insulin glulisine basal-bolus and twice-daily premixed analog insulin in type 1 diabetes mellitus patients during three standardized meals

Aims To evaluate the pharmacokinetics and pharmacodynamics of basal insulin glargine with mealtime insulin glulisine or twice daily 75/25 premixed neutral protamine insulin lispro and insulin lispro in individuals with type 1 diabetes during three standardized meals over a 24 hour duration and compare to physiologic insulin and glucose responses in healthy non-diabetic individuals. Methods Twelve healthy (4 male/8 female) and thirteen individuals with type 1 diabetes (8 male/5 female) were studied during three sequential standardized meals. Individuals with type 1 diabetes received either glargine and glulisine injected 5 minutes subcutaneously before each meal or premixed insulin lispro injected 5 minutes before breakfast and dinner in a randomized fashion separated by eight weeks. Results The incremental systemic insulin AUC, maximal insulin concentration, and rate of rise of systemic insulin (0-30 minutes) during all three meal intervals were similar between glargine/glulisine and healthy controls. Incremental glucose AUC with glargine/glulisine was similar to controls at lunch and dinner. With premix 75/25 insulin, insulin AUC was lower and incremental glucose AUC was greater at lunch compared to the healthy and glargine/glulisine. Hypoglycemic events before lunch were greater with premix insulin group than with glargine/glulisine (p < 0.0001). Conclusions Glargine/glulisine pharmacokinetics in type 1 diabetes can closely approximate physiologic insulin responses in healthy individuals during a day in which three standardized meals are consumed. Additionally, when glulisine is dosed only five minutes pre-meal, systemic insulin concentration rises as rapidly as prandial endogenous insulin levels. This present study compared glargine and glulisine administered in an approximate 50/50 proportion. Future studies of alternate meal times, meal content and differing premixed insulin preparations are indicated.