@article {Singh385, author = {Sumeet R. Singh, BScPhm MSc and Fida Ahmad, MSc and Avtar Lal, MD PhD and Changhua Yu, MD MSc and Zemin Bai, MD MSc and Heather Bennett, BPharm PhD}, title = {Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis}, volume = {180}, number = {4}, pages = {385--397}, year = {2009}, doi = {10.1503/cmaj.081041}, publisher = {CMAJ}, abstract = {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 {\textquotedblleft}grey literature{\textquotedblright} 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 A1c, 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: {\textendash}0.09\%, 95\% confidence interval [CI] {\textendash}0.16\% to {\textendash}0.02\%; for insulin aspart: {\textendash}0.13\%, 95\% CI {\textendash}0.20\% to {\textendash}0.07\%). We observed similar outcomes among patients with type 2 diabetes (weighted mean difference for insulin lispro: {\textendash}0.03\%, 95\% CI {\textendash}0.12\% to {\textendash}0.06\%; for insulin aspart: {\textendash}0.09\%, 95\% CI {\textendash}0.21\% to 0.04\%). Differences between long-acting insulin analogues and neutral protamine Hagedorn insulin in terms of hemoglobin A1c were marginal among adults with type 1 diabetes (weighted mean difference for insulin glargine: {\textendash}0.11\%, 95\% CI {\textendash}0.21\% to {\textendash}0.02\%; for insulin detemir: {\textendash}0.06\%, 95\% CI {\textendash}0.13\% to 0.02\%) and among adults with type 2 diabetes (weighted mean difference for insulin glargine: {\textendash}0.05\%, 95\% CI {\textendash}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.}, issn = {0820-3946}, URL = {https://www.cmaj.ca/content/180/4/385}, eprint = {https://www.cmaj.ca/content/180/4/385.full.pdf}, journal = {CMAJ} }