Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes

Abstract

Introduction: We compared the efficacy and safety of human regular insulin (HRI) versus rapid-acting insulin (RAI) in a type 2 diabetes population already using the V-Go insulin delivery device.

Research design and methods: This was a 14-week, multicenter, randomized, open-label, parallel-group, phase IV, non-inferiority study. Patients ≥21years of age, with inadequately controlled type 2 diabetes who were currently using the V-Go insulin delivery system with RAI, with glycated hemoglobin (HbA1c) ≥6.5% (≥48 mmol/L) to ≤12.5% (≤108 mmol/L) were randomized 1:1 to RAI continuation or switch to HRI. The primary outcome was estimated treatment difference (ETD) in HbA1c least-squares mean change from baseline at 14 weeks (prespecified non-inferiority hypothesis with 95% CI upper limit <0.4%). Primary analysis was by per protocol (PP); safety analysis was by intention to treat.

Results: We randomized 136 patients to continued RAI treatment (n=67) or HRI (n=69); 113 patients were included in the PP analysis (RAI, n=54; HRI, n=59). Mean change in HbA1c from baseline to study end was -0.60±1.1% (95% CI -0.90 to -0.29); -6.6±12.0 mmol/mol (95% CI -9.8 to -3.2) with HRI treatment and -0.38±1.3% (95% CI -0.70 to -0.05); -4.2±14.2 mmol/mol (95% CI -7.7 to -0.5) with RAI treatment, with ETD of -0.22% (95% CI -0.67 to 0.22); -2.4 mmol/mol (95% CI -7.3 to 2.4), p=0.007, confirming non-inferiority of HRI to RAI. No between-group differences in changes in total daily insulin doses, number of hypoglycemic values (≤70 mg/dL (≤39 mmol/L) or body weight were observed. No severe hypoglycemic events were reported. Direct pharmacy cost savings (-US$265.85; 95% CI -US$288.60 to -US$243.11; p<0.0001) were observed with HRI treatment.

Conclusions: Individuals with type 2 diabetes requiring insulin can be treated with V-Go wearable insulin delivery device using HRI, safely and effectively, and potentially at a much lower cost compared with RAI, which can lead to improved access to insulin therapy for these individuals.

Trial registration number: NCT03495908.

Keywords: costs and cost analysis; diabetes mellitus; insulin; insulin infusion systems; type 2.

Conflict of interest statement

Competing interests: PFM reports grants from Valeritas, Inc., and consulting fees from Janssen Pharmaceuticals, Novo Nordisk and Merck. DRS received grants from Valeritas during the conduct of the study; consulting fees from Valeritas, Novo Nordisk, Lilly USA, Boehringer Ingelheim, Janssen, AbbVie, Amarin. AG reports grants from Valeritas during the conduct of the study; consulting fees from Valeritas, Inc., Janssen Pharmaceuticals, Novo Nordisk and Merck. BB reports grants from Valeritas, Inc. acquired by Zealand Pharma during the conduct of the study; consulting fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Valeritas Eli Lilly, Amarin, Senseonics. RFG reports no financial disclosures. CN and JS II are employees of Zealand Pharma. BA-H reports consulting fees from Valeritas, Inc. acquired by Zealand Pharma during the conduct of the study.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Disposition of study participants. HbA1c, glycated hemoglobin; HRI, human regular insulin; ITT, intent-to-treat; PP, per protocol; RAI, rapid acting insulin; SMBG, self-monitoring of blood glucose.

Figure 2

Changes in HbA1c in the PP population. Changes and ETD in HbA1c from baseline. ETD are mean change (95% CI) derived from a mixed model analysis. Upper limit of 95% CI is

Figure 3

Pharmacy budget impact in PP population. Baseline and 14-week insulin costs per patient. Insulin cost is based on 30-day costs for HRI and RAI using published wholesale acquisition costs from ProspectoRx (database online). Elsevier, 2020, Tampa, Florida, USA (https://prospectorx.com/Home.aspx). Accessed November 28, 2019. At baseline, RAI was used to fill V-Go by both cohorts. ETD, estimated treatment difference; HRI, human regular insulin; PP, per protocol; RAI, rapid acting insulin.