Lower HbA1c achieved with CSII vs MDI for U-500R in type 2 diabetes
medwireNews: Continuous subcutaneous insulin infusion (CSII) of recombinant human regular U-500 insulin (U-500R) leads to greater glycated hemoglobin (HbA1c) reductions at a much lower dose than multiple daily injections (MDI) in people with type 2 diabetes, US research shows.
The phase 3 VIVID trial investigators found that, after 26 weeks of treatment, HbA1c fell from a mean baseline level of 8.8% (72.1 mmol/mol) to a mean of 7.5% (58.2 mmol/mol) in the 209 participants (mean age 58 years, 50% men) randomly assigned to receive U-500R via a specially-designed insulin pump.
George Grunberger (Grunberger Diabetes Institute, Bloomfield Hills, Michigan) and colleagues explain that the novel Omnipod DASHTM U-500 Insulin Management System (Insulet Corp., Acton, Massachusetts, USA) was developed to deliver U-500 insulin without the need for dose conversion that is typically required when using U-500 insulin with a U-100 pump.
For the 211 participants (mean age 57 years, 56% men) who were instead randomly assigned to receive U-500R via MDI, HbA1c fell from a mean of 8.8% (72.3 mmol/mol) at baseline to 7.9% (63.0 mmol/mol) at week 26, resulting in a significant 0.4% (4.6 mmol/mol) smaller reduction in HbA1c relative to CSII.
In addition, a significantly higher proportion of participants in the CSII group achieved HbA1c target values of either less than 7.0% (28.7 vs 18.4%) or less than 7.5% (52.6 vs 38.6%).
There was also a significant difference between the two groups in the change in fasting plasma glucose (FPG) over the course of the study. People using CSII demonstrated a mean fall of 33.9 mg/dL (1.9 mmol/L) whereas those using MDI experienced a mean increase of 1.7 mg/dL (0.1 mmol/L), resulting in a difference of 35.6 mg/dL (2.0 mmol/L).
Furthermore, Grunberger and co-authors report in Diabetes, Obesity & Metabolism that the greater improvements in HbA1c and FPG with CSII were achieved at a significantly lower total daily dose (TDD) of insulin.
Specifically, at week 26, the TDD was a mean 285 units (2.42 units/kg) in the CSII group and 333 units (2.90 units/kg) in the MDI group, which corresponded to increases of 2.8 and 51.3 units (0.09 and 0.42 units/kg), respectively, from baseline.
There were no significant differences between the two groups in bodyweight changes or in the rates of documented symptomatic and severe hypoglycemia, but people in the CSII group had a higher rate of nocturnal hypoglycemia events at both blood glucose cutoffs (<54 mg/dL and ≤70 mg/dL).
The researchers note that the nocturnal hypoglycemia rate in the CSII group was highest at week 8 but then decreased steadily until it converged with the rate in the MDI at week 23. Meanwhile, the TDD plateaued at around week 14.
“This suggests attainment of an insulin dose that allowed mitigation of nocturnal hypoglycemia without compromising glycemic control,” Grunberger et al remark.
They conclude: “With the obesity epidemic contributing to the prevalence of insulin resistance and rising insulin requirements among insulin-treated persons, the findings in this study provide timely confirmation about the efficacy and safety profile of U500-R MDI while also demonstrating U-500R CSII as a potential alternative delivery method.”
“Having these choices of delivery for U-500R could help overcome clinical challenges in this population related to injecting frequently or with large volumes to meet their insulin needs.”
By Laura Cowen
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