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)

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. Objective 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. 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 greater 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. Trial registration: ClinicalTrials.gov (NCT03243903) Funding Statement: Beijing QS Medical Technology Co., Ltd, China. This work was also supported by Grants 2016YFC1305600, 2016YFC1305603 from the Major Chronic Non-communicable Disease Prevention and Control Research. Declaration of Interests: 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. The other authors have nothing to disclose. Ethics Approval Statement: Before the study was commenced, approval was received from the Ethics Committee of Peking University People’s Hospital, and the study was conducted in accordance with the moral, ethical, and scientific principles of the declaration of Helsinki and the provisions of good clinical practice (GCP) in China. Written informed consent was obtained from all participants.