Improved glycaemic control with insulin glargine plus insulin lispro: a multicentre, randomized, cross-over trial in people with Type 1 diabetes.
OBJECTIVE
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.
University of Newcastle upon Tyne, Newcastle upon Tyne, UK. s.g.ashwell@ncl.ac.uk
S G
SG
Ashwell
S A
SA
Amiel
R W
RW
Bilous
U
U
Dashora
S R
SR
Heller
D A
DA
Hepburn
S D
SD
Shutler
J W
JW
Stephens
P D
PD
Home
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000069036:Insulin Glargine; D061268:Insulin Lispro; D007336:Insulin, Isophane / Q000009:adverse effects / Q000627:therapeutic use; D049528:Insulin, Long-Acting; D008297:Male; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D061268:Insulin Lispro; D007336:Insulin, Isophane; D049528:Insulin, Long-Acting