Efficacy, safety and acceptability of the new pen needle 34G × 3.5 mm: a crossover randomized non-inferiority trial; AGO 02 study

Abstract

Objective: Insulin injection aspects, such as fear of injection and pain, directly affect glycemic control, patient adherence and quality of life. Use of thinner and shorter needles could increase acceptance of injections. The aim of the study is to evaluate the non-inferiority of the new 34G × 3.5 mm needle compared to a 32G × 4 mm in patients with diabetes treated with insulin.

Methods: This is an open, randomized, two-period crossover, non-inferiority trial. Every treatment period lasted 3 weeks. Patients with type 1 or type 2 diabetes, treated with multiple daily insulin injections, were randomly assigned to receive a 34G × 3.5 mm or a 32G × 4 mm pen needle. The primary endpoint was the non-inferiority of the 34G × 3.5 mm in comparison with the 32G × 4 mm pen needle in terms of percentage absolute change of blood fructosamine (% |ΔFru|), using a non-inferiority margin of 20%.

Results: Overall 77 patients were randomized and 73 completed the study. Patients characteristics were: 52% male, 80.5% affected by type 1 diabetes, mean age 52 years (±14.6), mean BMI 24.5 kg/m² (±5.6), HbA1c 8% (±1.1) and baseline fructosamine level 350 µmol/l (±84). Mean fructosamine levels increased by 0.56 µmol/l with the 34G needle, while a reduction of 7.29 μmol/l was documented with the 32G needle. The difference between the two groups (7.84 μmol/l) was not statistically significant (p = .27). The % |ΔFru| between the two groups was 7.55% (95% CI 5.67–9.44), meeting the non-inferiority criterion. Glycemic variability, expressed as standard deviation of fasting blood glucose and post-prandial glucose, was not different between the two treatment groups (p = .63 and p = .77, respectively).

Conclusions: The 34G × 3.5 mm needle was non-inferior to the 32G × 4 mm needle regarding fructosamine levels and glycemic variability supporting the suitability of the 34G × 3.5 mm needle for insulin injection in patients with diabetes.

Clinical trial registration: NCT02690467

Keywords:

• Diabetes
• Insulin
• needle
• fructosamine
• crossover trial

Transparency

Declaration of funding

Pikdare SRL – Artsana Group SpA funded the study and supplied Pic Insupen 34G × 3.5 mm and 32G × 4 mm needles. Pikdare SRL – Artsana Group SpA did not interfere in the preparation of this article. The study design was inspired by the study of Hirsch et al.¹⁴.

Author contributions: A.N. and L.S. were involved in the conception and design of the study based on Hirsch et al.¹⁴; M.S. and G.L. performed data analysis; A.N., G.D.B., L.S., A.C.B., P.D’A. and G.M. were involved in the interpretation of the data; A.N., M.S. and G.D.B. were involved in the drafting of the paper; all the authors were involved in revising it critically for intellectual content; all authors gave the final approval of the version to be published and agree to be accountable for all aspects of the work.

Declaration of financial/other relationships

L.S. has disclosed that he has participated in an advisory panel for Pikdare SRL – Artsana Group SpA. A.C.B. has disclosed that he has participated in advisory panels for Lilly Italia Spa, Novo Nordisk Italia SpA, Johnson & Johnson SpA, Boehringer Ingelheim SpA, Pikdare SRL – Artsana Group SpA, Takeda SpA, Bayer SA, Sanofi SpA, AstraZeneca SpA and MSD Italia SpA. G.D.B., M.S., G.L., S.A., E.C., P.D’A., L.F., R.L., G.M. and A.N. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgements

The authors thank Stefano Signorini and Paolo Brambilla of the Department of Clinical Chemical Analyses, Hospital of Desio, Italy for central laboratory analyses.