Basal‐bolus insulin therapy in Type 1 diabetes: comparative study of pre‐meal administration of a fixed mixture of insulin lispro (50%) and neutral protamine lispro (50%) with human soluble insulin

Aims To ascertain whether pre‐meal administration of 50% insulin lispro and 50% neutral protamine lispro (NPL), given as a fixed mixture (Humalog® Mix50™, Eli Lilly) (Mix50), provides satisfactory glycaemic control throughout the day compared with pre‐meal human soluble (regular) insulin as a basal‐bolus regimen in people with Type 1 diabetes. Both regimens included bedtime human isophane (NPH) insulin. Methods This was a multinational, multicentre, randomized, open‐label, two‐period crossover comparison of two insulin treatments for two 12‐week periods in 109 patients with Type 1 diabetes. The protocol provided preliminary evaluations of dose requirements and recommendations for insulin dose adjustment when switching regimens on the basis of blood glucose (BG) values. Eight‐point BG profiles, frequency of hypoglycaemia, HbA 1c , insulin dose, time of injection, and frequency of snacking were assessed during each treatment. Results Total daily insulin dose was similar for both treatments, but the total pre‐meal doses were higher ( P  < 0.001) and the bedtime dose of isophane was lower ( P  < 0.001) with Mix50. The pre‐meal dose before breakfast and lunch, although statistically different ( P  = 0.006 and P  < 0.001, respectively), was of similar magnitude, but the pre‐evening meal dose was higher with Mix50 ( P  < 0.001). Median (interquartile range) time of insulin injection before meals was: Mix50 4.2 (25th percentile = 1.0; 75th percentile = 6.3) min, human soluble insulin 24.6 (25th percentile = 16.6; 75th percentile = 30.0) min. Pre‐meal and bedtime BG concentrations did not differ between treatments. The BG 2 h after the evening meal was lower with Mix50 (8.40 ± 2.95 mmol/l vs. 9.60 ± 3.47 mmol/l) ( P  = 0.049). BG after breakfast and lunch, mean HbA 1c , frequency of hypoglycaemia, frequency of snacks, and body weight were not different. Conclusion The use of Mix50 in a basal‐bolus regimen achieved similar control of pre‐meal BG to human soluble insulin, and overall glycaemic control and hypoglycaemia risk were equivalent. This suggests that Mix50 can provide an adequate supply of insulin to control BG between meals while providing the convenience of injecting immediately before meals. Diabet. Med. 19, 917–923 (2002)