Human regular U-500 insulin via continuous subcutaneous insulin infusion versus multiple daily injections in adults with type 2 diabetes: The VIVID study

Diabetes Obes Metab. 2020 Mar;22(3):434-441. doi: 10.1111/dom.13947. Epub 2020 Jan 26.

Abstract

Aim: To compare the safety and efficacy of U500-R delivered by a novel, specifically designed U500-R insulin pump with U-500R delivered by multiple daily injections (MDI).

Methods: The phase 3 VIVID study randomized people with type 2 diabetes to U-500R by continuous subcutaneous insulin infusion (CSII) or MDI. Participants (aged 18-85 years) had HbA1c ≥7.5% and ≤12.0% and a total daily dose of insulin >200 and ≤600 U/day. After a 2-week transition to three times daily injections of U-500R, participants were treated for 24 weeks with U-500R by CSII or MDI. Treatment arms were compared using mixed model repeated measures analysis.

Results: The study randomized 420 participants (CSII: 209, MDI: 211) with 365 completers. Mean changes from baseline were: HbA1c, -1.27% (-13.9 mmol/mol) with CSII and -0.85% (-9.3 mmol/mol) with MDI (difference - 0.42% [-4.6 mmol/mol], P <0.001); fasting plasma glucose, -33.9 mg/dL (-1.9 mmol/L) with CSII and 1.7 mg/dL (0.09 mmol/L) with MDI (difference - 35.6 mg/dL [-2.0 mmol/L], P <0.001); total daily dose, 2.8 U with CSII and 51.3 U with MDI (P < 0.001). Weight changes and rates of documented symptomatic and severe hypoglycaemia were similar between groups; the CSII group had a higher rate of nocturnal hypoglycaemia.

Conclusions: In type 2 diabetes requiring high doses of insulin, both methods of U-500R delivery lowered HbA1c. However, the CSII group attained greater HbA1c reduction with significantly less insulin. Individualized dose titration will be important to balance glycaemic control with hypoglycaemia risk.

Keywords: clinical trial; continuous subcutaneous insulin infusion; insulin resistance; insulin therapy; randomized trial; type 2 diabetes..

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Injections, Subcutaneous
  • Insulin / therapeutic use
  • Insulin Infusion Systems

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin