Continuous subcutaneous insulin infusion (CSII) or insulin pumps can consist of either conventional pumps, which deliver a bolus infusion of insulin based on the self-monitoring of blood glucose, or sensor-augmented pumps (SAP), which continuously measure interstitial glucose levels. A close-loop system involves SAP technology in conjunction with an algorithm that automatically adjusts insulin dosing based on blood glucose. In hybrid closed-loop systems, only basal insulin administration is automatically adjusted or advanced, and bolus infusions are also administered automatically.
Insulin pumps generally use rapid-acting insulin (RAI) formulations (i.e., insulin lispro, aspart, or glulisine); however, a drawback of RAI formulations is that they do not achieve adequate postprandial glucose control. To optimize glycemic control, attention has focused on the use of fast-acting insulin aspart and ultra-rapid lispro, which naturally mimic endogenous insulin secretion, resulting in more efficient glucose lowering and time in range (TIR). However, little is known about the overall efficacy and safety of these formulations in type 1 diabetes when used in CSII systems.
Investigators conducted a systematic review and meta-analysis based on studies retrieved from PubMed and Cochrane Central Registration of Controlled Trials through May 9, 2022. Inclusion criteria were randomized, controlled trials involving patients with type 1 diabetes who used CSII; insulin treatment duration of at least 2 weeks; and the use of ultra-rapid insulin analogues compared with RAIs.
The primary outcome was the percentage of time that the glucose was in target range (blood glucose of 70-180 mg/dL) throughout 24 hours (the TIR). Secondary outcomes included 24-hour percentage of time in hypoglycemia (<70 mg/dL) or hyperglycemia (>180 mg/dL), 2-hour postprandial glucose increment after a meal test, hemoglobin A1c values, and average number of units of insulin per day at study endpoint. Safety outcomes included the incidence of severe hypoglycemia, which was defined as the number of patients with at least one hypoglycemic episode that required assistance and events of unplanned infusion set changes.
The researchers identified nine articles involving 1,156 patients that met the study inclusion criteria. Of the six studies that examined TIR, ultra-rapid insulin analogues resulted in a higher nonsignificant 24-hour percentage of TIR (mean difference 1.1%; 95% CI, 0.11-2.11) and significantly less time spent in hypoglycemia (mean difference –0.47%; 95% CI, –0.63 to –0.30) compared with RAIs. There was no difference in time spent in hyperglycemia (mean difference –0.14; 95% CI, –1.22-0.94) between the two groups.
While hemoglobin A1c levels did not vary between the ultra-rapid insulin group and RAI group (mean difference –0.10%; 95% CI, –0.35-0.14), the former agents were associated with a significant decrease in both 1-hour (mean difference –23.71 mg/dL; 95% CI, –33.30 to –14.12) and 2-hour (mean difference –19.25 mg/dL; 95% CI, –27.30 to –11.19) postprandial glucose levels. There was no significant difference in average insulin dose for the ultra-rapid insulins and RAIs. The time spent in hypo- or hyperglycemia, 1- and 2-hour postprandial glucose levels and hemoglobin A1c, and the average insulin doses were similar in subgroup analyses (i.e., irrespective of the particular type of insulin administered, the study design, or the CSII system type).
Based on information from seven studies, there were 60% higher odds of significant differences in unplanned infusion set changes in the ultra-rapid insulin group compared with the RAI group (odds ratio [OR] 1.6; 95% CI, 1.26-2.03). This difference was attributable to the use of an SAP (OR 1.77; 95% CI, 1.37-2.29) rather than a hybrid closed-loop system (OR 0.89; 95% CI, 0.48-1.45). Subgroup analyses were similar for this parameter as well.
Severe hypoglycemia was uncommon in both the ultra-rapid and RAI groups and was not subject to meta-analysis.
This study provides pharmacists with reassurance regarding the effective use of ultra-rapid insulins in CSII and demonstrates that they provide better postprandial glucose control, although their use may result in more infusion set changes.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
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Published January 10, 2023