Clinical review: Hypoglycemia with intensive insulin therapy: a systematic review and meta-analyses of randomized trials of continuous subcutaneous insulin infusion versus multiple daily injections.

CONTEXT: Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear.

OBJECTIVE: The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia.

DATA SOURCES: We searched electronic databases between 2002 and March 2008.

STUDY SELECTION: We selected published randomized trials of CSII vs. MDI.

DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events.

DATA SYNTHESIS: We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2%; 95% confidence interval (CI), -0.3, -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95% CI, -0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; P(interaction) = 0.03). Outcomes were not different in patients with type 2 diabetes.

CONCLUSIONS: Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data.