Insulin Analogs vs Regular Human Insulin for Type 2 Diabetes

There are no clear benefits or harms to choosing short-acting insulin analogs over regular human insulin for nonpregnant, adult individuals with type 2 diabetes.

There are no clear benefits or harms to choosing short-acting insulin analogs over regular human insulin for nonpregnant adult individuals with type 2 diabetes, according to a literature review published in Cochrane Database of Systematic Reviews.

This systematic review compared the effects of short-acting insulin analogs (insulin aspart, insulin glulisine, and insulin lispro) with those of regular human insulin in adult nonpregnant individuals with type 2 diabetes. Data analyzed from randomized, controlled clinical trials published in all languages were found through searches of Cochrane Central Register of Controlled Trials,, Embase, MEDLINE, and the World Health Organization International Clinical Trials Registry Platform through October 31, 2018. Review authors extracted data and assessed bias risk independently.

In the 10 trials eligible for inclusion, 1388 participants received short-acting insulin analogs and 1363 received regular human insulin (N = 2751). Interventions lasted between 24 to 104 weeks (mean duration, 41 weeks). The trials showed a low incidence of severe hypoglycemic events and no clear differences between intervention arms. The glycosylated hemoglobin A1c mean difference change overall was -0.03% (95% CI, -0.16 to 0.09; P =.60 in 9 trials with 2608 participants), but with low-certainty evidence and 95% prediction ranging from -0.31% to 0.25%. The number of nonsevere hypoglycemic episodes overall was 0.08 events/participant/month (95% CI, 0.00-0.16; P =.05 in 7 trials with 2667 participants), but with very low-certainty evidence and 95% prediction ranging from -0.03 to 0.19.

Six of the trials (n = 2509) used different methods to assess severe hypoglycemia, so that the results could not be summarized with meta-analysis. No trials included all-cause mortality as a primary outcome or investigated long-term effects, and results concerning nocturnal hypoglycemic episodes were questionable. None of the trials were blinded, making risk of detection and performance bias very high, and several showed inconsistencies in how methods and results were reported.

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The researchers concluded that although no clear difference could be seen between the two treatment arms overall, the certainty of evidence was poor, with sparse evidence regarding patient-relevant outcomes such as diabetes complications and all-cause mortality. They suggested that patients and doctors should “look at the advantages and disadvantages of different medication regimes, and choose a cost-effective treatment, given the individual requirements of the patient.”

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Fullerton B, Siebenhofer A, Jeitler K, et al. Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2018;12:CD013228.