Hypoglycemia with Intensive Insulin Therapy: A Systematic Review and Meta-Analyses of Randomized Trials of Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections

Abstract

Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear. The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia. We searched electronic databases between 2002 and March 2008. We selected published randomized trials of CSII vs. MDI. Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events. 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. 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.