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

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.