Summary of Meta-Analyses and Systematic Reviews Comparing Rapid-Acting insulin Analogues to Short-Acting Regular Human Insulin

 

Reference	Studies	Results
Siebenhofer et al 20061	Studies published up to September 2005 Lispro (6 trials) Aspart (1 trial) No glulisine studies	HbA1c: no significant difference Hypoglycaemia: no significant difference
Singh et al 20092	Studies published up to 2007 Included premix formulations Lispro (11 trials) Aspart (4 trials) No glulisine studies	HbA1c: no significant difference Risk of hypoglycaemia: no significant difference
Mannucci et al 20093	Studies published up to January 2008 Lispro (7 trials) Aspart (4 trials) Glulisine (2 trials) Included premix formulations	HbA1c: -0.10% in favour of analogues [95% CI, -0.01 to -0.19]. In 3 studies, blood glucose was significantly lower with analogues after breakfast (by 0.7 mmol/L) and dinner (by 0.6 mmol/L) (both P < 0.001). Severe hypoglycaemia: no significant difference
Rys et al 20114	Studies published up to July 2009  Included premix formulations Only studies on aspart (6 trials) or BIAsp (4 trials)	HbA1c: no significant difference PPG: daily mean PPG lower by 1.18 mmol/L [95% CI,-1.88 to -0.47] with Aspart* Risk of hypoglycemia: no significant difference
Heller et al 20135	Patient-level data from trials comparing aspart with human insulin Trials in type 1 diabetes (6 trials, n. 1909), type 2 diabetes (3 trials, n. 219), and types 1 and 2 diabetes combined (1 trial, n. 110)	HbA1c: -0.10% in favour of Aspart [95% CI, -0.15 to -0.04], p<0.001 PPG: significantly lower by 0.47 mmol/L [95% CI, -0.70 to -0.25]; (p<0.001) with Aspart. Hypoglycaemia: no significant difference Nocturnal hypoglycaemia: significantly lower with Aspart: RR, 0.76 [95% CI, 0.67-0.85]; (p < 0.001)

BIAsp = biphasic insulin aspart; CI = confidence interval; HbA_1c = glycated haemoglobin; PPG = postprandial glucose.
*Including studies of aspart and BIAsp

References:

1. Siebenhofer A, Plank J, Berghold A, et al. Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus. In: Siebenhofer A, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2006:CD003287. doi:10.1002/14651858.CD003287.pub4.
2. Singh SR, Ahmad F, Lal A, Yu C, Bai Z, Bennett H. Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis. Can Med Assoc J. 2009;180(4):385-397. doi:10.1503/cmaj.081041.
3. Mannucci E, Monami M, Marchionni N. Short-acting insulin analogues vs. regular human insulin in type 2 diabetes: a meta-analysis. Diabetes, Obes Metab. 2009;11(1):53-59. doi:10.1111/j.1463-1326.2008.00934.x.
4. Rys P, Pankiewicz O, Łach K, Kwaskowski A, Skrzekowska-Baran I, Malecki MT. Efficacy and safety comparison of rapid-acting insulin aspart and regular human insulin in the treatment of type 1 and type 2 diabetes mellitus: A systematic review. Diabetes Metab. 2011;37(3):190-200. doi:10.1016/j.diabet.2010.12.003.
5. Heller S, Bode B, Kozlovski P, Svendsen AL. Meta-analysis of insulin aspart versus regular human insulin used in a basal-bolus regimen for the treatment of diabetes mellitus. J Diabetes. 2013;5(4):482-491. doi:10.1111/1753-0407.12060.