Insulin delivery with a needle-free insulin injector versus a conventional insulin pen in Chinese patients with type 2 diabetes mellitus: A 16-week, multicenter, randomized clinical trial (the FREE study)

Linong Ji, Leili Gao, Liming Chen, Yangang Wang, Zhongshu Ma, Xingwu Ran, Zilin Sun, Xiangjin Xu, Guixia Wang, Lixin Guo, Zhongyan Shan, Linong Ji, Leili Gao, Liming Chen, Yangang Wang, Zhongshu Ma, Xingwu Ran, Zilin Sun, Xiangjin Xu, Guixia Wang, Lixin Guo, Zhongyan Shan

Abstract

Background: Insulin therapy is poorly accepted by patients with type 2 diabetes mellitus (T2DM). A needle-free insulin injector has been developed for patients who fear injections or are reluctant to initiate insulin therapy when it is clearly indicated. The objective of this trial was to evaluate the glucose-lowering effect, tolerability, patient satisfaction and compliance with insulin treatment via a needle-free insulin injector (NFII) compared with insulin treatment via a conventional insulin pen (CIP) in patients with T2DM.

Methods: A total of 427 patients with T2DM were enrolled in a prospective, multicenter, randomized, open-label study, and were randomly assigned 1:1 to receive 16 weeks' treatment with basal insulin or premixed insulin administered either by a NFII or CIP.

Trial registration: ClinicalTrials.gov (NCT03243903).

Findings: In the 412 patients who completed the study, the adjusted mean reduction of HbA1c from baseline at week 16 in the NFII group was 0.55% (95% CI -0.71, -0.39), which was non-inferior and statistically superior to the HbA1c reduction in the CIP group (0.26%, 95% CI -0.42, -0.11). Patients in the NFII group showed significantly higher treatment satisfaction scores than those in the CIP group (mean scores, 8.17 ± 1.78 vs. 7.21 ± 2.22, respectively; p<0.0001). The occurrence of hypoglycemia was similar in the two groups, and the NFII group showed reduced incidences of skin scratches, indurations and lower VAS pain scores.

Interpretation: Insulin therapy through needle-free injector showed a non-inferior glycemic-lowering effect and a significantly enhanced level of patient satisfaction with insulin treatment compared with conventional insulin therapy through needle injections. In addition, the needle-free injector also had a better safety profile.

Funding: This study were funded by Beijing QS Medical Technology Co., Ltd, as well as The Major Chronic Non-communicable Disease Prevention and Control Research.

Keywords: Diabetes Mellitus; Efficacy; HbA1c; Insulin; Needle-free injector; Safety; Type 2.

Conflict of interest statement

Linong Ji receives consulting fees from Beijing QS Medical Technology Co. He also reports grants and personal fees from Novo Nordisk, Merck, Bristol-Myers Squibb, Novartis, Sanofi, MSD, AstraZeneca, and Roche, and personal fees from Eli Lilly, Takeda, Bayer, and Boehinger Ingelheim, outside the submitted work. Leili Gao reports grants from Beijing QS Medical Technology Co. Ltd, China, and grants from the Major Chronic Non-communicable Disease Prevention and Control Research during the conduct of the study. The other authors report grants from Beijing QS Medical Technology Co. Ltd during the conduct of the study.

© 2020 Published by Elsevier Ltd.

Figures

Fig. 1
Fig. 1
Flow of patients in the trial. NFII = needle-free insulin injector; CIP = conventional insulin pen.
Fig. 2
Fig. 2
HbA1c decline from baseline (%) in the two groups after 16 weeks’ treatment. NFII = needle-free insulin injector, CIP = conventional insulin pen. Data are presented as mean values ± SEM. **p<0.01 between the two groups.
Fig. 3
Fig. 3
7-point SMBG values (mmol/L) and insulin dosages in the two groups from baseline to the end of trial. BG = blood glucose concentration; CIP = conventional insulin pen; NFII = needle-free insulin injector. Data are presented as mean values ± SEM.
Fig. 4
Fig. 4
Treatment satisfaction scores in the two groups at the end of the trial. CIP = conventional insulin pen; NFII = needle-free insulin injector. Data are presented as mean values ± SEM. ***p<0.01 between the groups.

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