Severe hypoglycaemia - PUMP X Multiple Daily Injections

Review Article

Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta-analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion

J. C. Pickup and A. J. Sutton* Metabolic Unit, King’s College London School of Medicine, Guy’s Hospital, London and *Department of Health Sciences, University of Leicester, Leicester, UK Accepted 8 April 2008

Abstract

Aims Continuous subcutaneous insulin infusion (CSII) is a recommended treatment for reducing severe hypoglycaemia in Type 1 diabetes, but the change in hypoglycaemia compared with multiple daily insulin injections (MDI) is unclear. We therefore conducted a meta-analysis comparing severe hypoglycaemia and glycaemic control during CSII and MDI.

Methods Databases and literature (1996 – 2006) were searched for randomized controlled trials (RCTs) and before/after studies of ≥ 6 months’ duration CSII and with severe hypoglycaemia frequency > 10 episodes/100 patient years on MDI.

Results In 22 studies (21 reports), severe hypoglycaemia during MDI was related to diabetes duration (P = 0.038) and was greater in adults than children (100 vs. 36 events/100 patient years, P = 0.036). Severe hypoglycaemia was reduced during CSII compared with MDI, with a rate ratio of 2.89 (95% CI 1.45 to 5.76) for RCTs and 4.34 (2.87 to 6.56) for before/after studies [rate ratio 4.19 (2.86 to 6.13) for all studies]. The reduction was greatest in those with the highest initial severe hypoglycaemia rates on MDI (P < 0.001). The mean difference in glycated haemoglobin (HbA1c) between treatments was less for RCTs [0.21% (0.13–0.30%)] than in before/after studies [0.72% (0.55–0.90%)] but strongly related to the initial HbA1c on MDI (P < 0.001).

Conclusions The severe hypoglycaemia rate in Type 1 diabetes was markedly less during CSII than MDI, with the greatest reduction in those with most severe hypoglycaemia on MDI and those with the longest duration of diabetes. The biggest improvement in HbA1c was in those with the highest HbA1c on MDI.

Diabet. Med. 25, 765–774 (2008)

Keywords Hypoglycaemia, Type 1 diabetes mellitus, meta-analysis, insulin pump therapy, continuous subcutaneous insulin infusion, glycaemic control

Abbreviations B/A, before/after design; CI, confidence interval; CSII, continuous subcutaneous insulin infusion; HbA1c, glycated haemoglobin; MDI, multiple daily injections; RCT, randomized controlled trial; SE, standard error