Efficacy and Safety of Rapid-Acting Insulin Analogs in Special Populations with Type 1 Diabetes or Gestational Diabetes: Systematic Review and Meta-Analysis

Abstract

IntroductionTo assess the efficacy and safety of three available rapid-acting insulin analogs (insulins lispro, aspart and glulisine, respectively) in pregnant women, children/adolescents and people using continuous subcutaneous insulin infusion (CSII) with type 1 diabetes.MethodsPubMed, EMBASE and Cochrane Reviews were searched electronically, and their bibliographies examined to identify suitable studies for review and inclusion in a meta-analysis. Eligible studies were randomized controlled trials that reported data on relevant clinical outcomes. A different reviewer abstracted data for each of the three subpopulations, and one reviewer abstracted data for all three. Any differences were resolved by consensus or by consulting a fourth reviewer.ResultsIn people on CSII, rapid-acting insulin analogs lowered postprandial plasma glucose post-breakfast to a greater extent than did regular human insulin (RHI) (mean difference: − 1.63 mmol/L [95% confidence interval − 1.71; − 1.54]), with a comparable risk of hypoglycemia and a trend for lower glycated hemoglobin. In the pediatric population, glycemic control was similar with rapid-acting insulin analogs and RHI, with no safety concerns. Meta-analysis indicated severe hypoglycemic events were comparable for rapid-acting insulin analogs versus RHI (risk difference: 0.00 [95% confidence interval − 0.01; 0.01]). In the pregnancy group, insulin lispro and insulin aspart were safe and effective for both mother and fetus, with glycemic control being at least as good as with RHI. There were no data on insulin glulisine during pregnancy.ConclusionRapid-acting insulin analogs appear generally safe and effective in these special populations; however, additional trials would be helpful.FundingNovo Nordisk A/S.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0411-7) contains supplementary material, which is available to authorized users.

Insulin Therapy in Adults with Type 1 Diabetes Mellitus: a Narrative Review

“…In the few trials that have studied the use of prandial insulins administered via CSII, similar or better HbA1c values and rates of hypoglycemic episodes were reported for aspart and lispro compared to regular human insulin [77,86]. A recent meta-analysis of patients with T1DM receiving CSII showed that rapid-acting insulin analogues reduced postprandial glucose better than did regular human insulin, with a similar risk of hypoglycemia and a trend toward lower HbA1c [87].…”

“…Treatment adherence is generally better with the pen than with the syringe/vial modality [90]. Among the rapid-acting prandial insulin analogues used in CSII, somewhat better efficacy was seen for aspart than lispro and glulisine in one trial [87], and in another trial aspart seemed to have greater stability in the pump and lower rates of infusion set occlusions [91]. However, a third trial found no significant differences among glulisine, aspart, and lispro for HbA1c, severe hypoglycemia, or infusion set occlusions [92].…”

Persistent heterogeneity in diabetes technology reimbursement for children with type 1 diabetes: The SWEET perspective

“…Intensive insulin treatment improves glycemic control and reduces the risk for acute and long‐term complications. The use of insulin analogs allows children to improve glycemic control with more flexibility in their daily lives, reducing the risk of nocturnal hypoglycemia and postprandial hyperglycemia compared to human regular and intermediate acting insulins . The current report shows a generally satisfactory reimbursement of all types of insulin in Europe for children with T1D, which illustrates the positive trend in insulin reimbursement in the last decade.…”

Insulin Therapy in Gestational Diabetes

“…The most important confounding factor is glycemic control. Although some case reports indicate an association between the use of insulin lispro and the risk of teratogenesis [63], another meta-analysis supports the fact that it is safe for use [64]. This risk could be explained by mitogenesis stimulation by binding with a higher affinity for IGF-1 receptors.…”