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

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: ‐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 A1c 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 longterm diabetes-related complications or death. Interpretation: Rapid- and long-acting insulin analogues offer little benefit relative to conventional insulins in terms