Can using ultra-rapid lispro in patients with type 1 diabetes using subcutaneous insulin infusion improve glucose control after meals?

This study compared the effectiveness and safety of ultra-rapid lispro (URLi; Lyumjev^TM) to lispro (Humalog) in patients with type 1 diabetes (T1D) on continuous subcutaneous insulin infusion (CSII). The authors concluded that URLi was similarly effective and provided improved postprandial glucose (PPG) control with reduced hypoglycemia in these patients.

Patients with T1D depend on insulin injections to control their blood glucose (sugar). They commonly need a basal insulin that slowly releases insulin throughout the day and rapid insulin injection such as lispro at mealtimes. CSII or insulin pump therapy is a wearable device that provides a steady stream of insulin in the body. It mimics normal physiological insulin secretion in patients with T1D.

After meals, glucose levels (postprandial glucose; PPG) tend to be very high. Therefore, rapid insulins need to lower this glucose in order to avoid severe diabetic complications such as ketoacidosis (a buildup of acids in the blood). URLi is an ultra-rapid-acting insulin with accelerated absorption. Compared to lispro, subcutaneous injections with URLi are shown to have a faster onset and earlier glucose-lowering effects. Accelerated absorption and good PPG control have been observed when URLi is given through CSII in adults with TD1.

However, whether URLi is at least similarly safe and effective to lispro in patients with T1D using CSII remains under investigation.

432 patients with T1D using CSII were included in this 16-week study. 215 patients were randomly assigned to receive URLi while 217 patients received lispro. HbA1c (blood glucose control over the past 2-3 months) changes from the beginning of the study to week 16 were measured to assess whether URLi produced the same benefit as lispro.

URLi achieved similar levels of HbA1c after 16 weeks. At 16 weeks, 18.9% of patients in the URLi group and 20.8% of the lispro group achieved a target HbA1c level below 7%. 1 hour and 2 hours after meals, there were significantly lower blood glucose levels in patients treated with URLi compared to lispro. The time patients spent with normal blood glucose levels was similar between groups.

Hypoglycemia (dangerously low blood glucose levels) during the night and after meals was significantly less common in the URLi group compared to the lispro group. Patients in the URLi group also spent significantly less time in hypoglycemia compared to the lispro group. However, side effects such as infusion reactions were more common with URLi (19.1%) compared to lispro (6.9%) or infusion site pain (15.8% with URLi vs 2.8% with lispro). 

The study found that URLi administration via CSII provided good glycemic control with acceptable safety and lower hypoglycemia rates compared to lispro in patients with T1D.

The follow-up period was very short. Longer-term studies are needed. This study was funded by Eli Lilly and Company, the manufacturer of URLi.