Twenty-two studies, in 21 publications, were included (n=1,414 patients); six were RCTs and 16 were before-and-after studies. Most studies had less than 10% withdrawals or discontinuations. No studies clearly reported blinding of the assessment of the severe hypoglycaemia rate. One RCT reported satisfactory concealment of allocation and a description of the randomisation method.
Compared with multiple daily insulin injections, severe hypoglycaemia was reduced with continuous subcutaneous insulin infusion. When pooling all the studies, the rate ratio was 4.19 (95% CI 2.86 to 6.13; 22 studies); when pooling RCTs it was 2.89 (95% CI 1.45 to 5.76; six RCTs); and when pooling before-and-after studies it was 4.34 (95% 2.87 to 6.56; 16 studies). Significant heterogeneity was observed when pooling all studies (I2=84.2%).
Meta-regression revealed that the greatest reduction in severe hypoglycaemia was seen in patients with the highest initial severe hypoglycaemia rate on multiple daily insulin injections (p<0.001). It also showed that severe hypoglycaemia during multiple daily insulin injections was significantly related to the diabetes duration (p=0.038) and was significantly greater in adults than in children (p=0.036).
There was better glycaemic control with continuous infusion, than with multiple daily injections, with a mean difference in HbA1c of 0.62% (95% CI 0.47 to 0.78; 22 studies). Significant heterogeneity was observed for this outcome (I2=83.8%).
Subgroup analyses, by study design, showed that the mean difference in HbA1c was significantly larger when pooling before-and-after studies compared with pooling RCTs (p=0.04), but the pooled rate ratios of severe hypoglycaemia from RCTs and from before-and-after studies were not significantly different.
No evidence of publication bias was found.