Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes.

AIMS: To compare blood glucose control using insulin glargine + insulin lispro with that on NPH insulin + unmodified human insulin in adults with Type 1 diabetes managed with a multiple injection regimen. METHODS: In this 32-week, five-centre, two-way cross-over study, people with Type 1 diabetes (n = 56, baseline HbA1c 8.0 +/- 0.8%) were randomized to evening insulin glargine + mealtime insulin lispro or to NPH insulin (once- or twice-daily) + mealtime unmodified human insulin. Each 16-week period concluded with a 24-h inpatient plasma glucose profile. RESULTS: HbA1c was lower with glargine + lispro than with NPH + human insulin 7.5 vs. 8.0%, difference -0.5 (95% CI -0.7, -0.3) %, P < 0.001]. This was confirmed by an 8% lower 24-h plasma glucose area under the curve (AUC) (187 vs. 203 mmol l(-1) h(-1), P = 0.037), a 24% reduction in plasma glucose AUC > 7.0 mmol/l1 (47 vs. 62 mmol l(-1) h(-1), P = 0.017) and a 15% lower post-prandial plasma glucose AUC (75 vs. 88 mmol l(-1) h(-1), P = 0.002). There was no reduction in night-time plasma glucose AUC or increase in plasma glucose area < 3.5 mmol/l. Monthly rate of nocturnal hypoglycaemia was reduced by 44% with glargine + lispro (0.66 vs. 1.18 episodes/month, P < 0.001). CONCLUSIONS: Compared with NPH insulin + unmodified human insulin, the combination of insulin glargine with a rapid-acting insulin analogue as multiple-injection therapy for Type 1 diabetes improves overall glycaemic control as assessed by HbA1c and 24-h plasma glucose monitoring to a clinically significant degree, together with a reduction in nocturnal hypoglycaemia.