Efficacy, safety and acceptability of the new pen needle 33G × 4 mm. AGO 01 study

Abstract

Objectives:

Adherence to insulin therapy can be threatened by pain and needle fear. This cross-over randomized non-inferiority trial evaluated a new Pic Insupen 33G × 4 mm needle vs. a 32G × 4 mm needle in terms of metabolic control, safety and acceptability in patients with diabetes treated with insulin.

Research design and methods:

We used a centralized, permuted block randomization, stratified by center and maximum insulin dose per single injection. Subjects used the two needles in two 3 week treatment periods. The primary endpoint was the absolute percentage variation of the blood fructosamine between the two treatments (% |ΔFru|). Additional endpoints were: glycemic variability, total insulin doses, body weight, severe hypoglycemic episodes, leakage at injection sites and pain measured by visual analogue scale. Equivalent glycemic control was defined a priori as % |ΔFru| (including 95% CI) within 20%.

Results:

Of 87 subjects randomized, 77 completed the study (median age 53.1 [IR 42.3–61.2], median BMI 24.3 Kg/m² [IR 21.3–28.5], median duration of insulin therapy [in months] 141.4 (IR 56.3–256.9), median baseline HbA1c 7.9% [IR 7.2–8.8]). The % |ΔFru| was 7.93% (95% CI 6.23–9.63), meeting the non-inferiority criterion. The fasting blood glucose standard deviation was 46.2 (mean 154.6) with the 33G needle and 42.8 (mean 157.3) with the 32G needle (p = 0.42). Insulin daily dose and patients’ weight did not show any statistically significant variation. We observed 95 episodes of symptomatic hypoglycemia with the 33G needle and 96 with the 32G needle. One episode of severe hypoglycemia was documented in the latter group. As for insulin leakage we observed 37.55 episodes per 100 patient-days with the 33G needle and 32.21 episodes per 100 patient-days with the 32G needle (p = 0.31). Patients reported less pain with the 33G × 4 mm needle (p = 0.05).

Study limitations:

Study sample was mainly composed of adults with type 1 diabetes and study was not blinded.

Conclusions:

The 33G needle is not inferior to the 32G needle in terms of efficacy and safety, with reduced pain and no difference in insulin leakage.

Clinical trial registration:

NCT01745549.

Keywords: :

• Cross-over studies
• Diabetes
• Fructosamine
• Needle
• Pain

Transparency

Declaration of funding

Artsana SpA/Pic Solutions Division funded the study and supplied Pic Insupen 33G × 4 mm and 32 × 4 mm needles. Artsana SpA/Pic Solutions Division did not interfere in the preparation of this article.

Declaration of financial/other relationships

A.B. has disclosed that he has received grants from Eli Lilly and Johnson & Johnson, is on the speaker’s bureau for Novo Nordisk and Boehringer Ingelheim. A.C. has disclosed that she has received grants from Artsana. A.N. has disclosed that he has received grants from Novo Nordisk and Sanofi Aventis, and is a consultant for Novo Nordisk, Astrazeneca, Sanofi Aventis. M.V., M.S., F.B., A.C., A.G., S.L., E.M., F.P., A.P., L.R., L.S., and E.V. 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 1 and 2 have no relevant financial or other relationships to disclose. CMRO peer reviewer 3 has disclosed that he is an employee of Becton Dickinson and Company, Franklin Lakes, NJ, USA.