Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis

Background: Although insulin analogues are commonly prescribed for the management of diabetes mellitus, there is uncertainty regarding their optimal use. We conducted meta-analyses to compare the outcomes of insulin analogues with conventional insulins in the treatment of type 1, type 2 and gestational diabetes. Methods: We updated 2 earlier systematic reviews of the efficacy and safety of rapid- and long-acting insulin analogues. We searched electronic databases, conference proceedings and "grey literature" up to April 2007 to identify randomized controlled trials that compared insulin analogues with conventional insulins. Study populations of interest were people with type 1 and type 2 diabetes (adult and pediatric) and women with gestational diabetes. Results: We included 68 randomized controlled trials in the analysis of rapid- acting insulin analogues and 49 in the analysis of long-acting insulin analogues. Most of the studies were of short to medium duration and of low quality. In terms of hemoglobin A(1c), we found minimal differences between rapid- acting insulin analogues and regular human insulin in adults with type 1 diabetes (weighted mean difference for insulin lispro: -0.09%, 95% confidence interval [CI] -0.16% to -0.02%; for insulin aspart: -0.13%, 95% CI -0.20% to -0.07%). We observed similar outcomes among patients with type 2 diabetes (weighted mean difference for insulin lispro: -0.03%, 95% CI -0.12% to -0.06%; for insulin aspart: -0.09%, 95% CI -0.21% to 0.04%). Differences between long-acting insulin analogues and neutral protamine Hagedorn insulin in terms of hemoglobin A(1c) were marginal among adults with type 1 diabetes (weighted mean difference for insulin glargine: -0.11%, 95% CI -0.21% to -0.02%; for insulin detemir: -0.06%, 95% CI -0.13% to 0.02%) and among adults with type 2 diabetes (weighted mean difference for insulin glargine: -0.05%, 95% CI -0.13% to 0.04%; for insulin detemir: -0.13%, 95% CI 0.03% to 0.22%). Benefits in terms of reduced hypoglycemia were inconsistent. There were insufficient data to determine whether insulin analogues are better than conventional insulins in reducing long-term diabetes-related complications or death. Interpretation: Rapid- and long-acting insulin analogues offer little benefit relative to conventional insulins in terms of glycemic control or reduced hypoglycemia. Long-term, high-quality studies are needed to determine whether insulin analogues reduce the risk of long-term complications of diabetes.