Original article
Safety and Efficacy of Insulin Therapy Delivered via a 4mm Pen Needle in Obese Patients With Diabetes

Data Previously Presented: These data were presented in part at the 2013 American Diabetes Association annual meeting in Chicago, IL.
https://doi.org/10.1016/j.mayocp.2014.12.014Get rights and content

Abstract

Objective

To determine whether insulin delivered via a 4-mm × 32-gauge pen needle (PN) provides equivalent glycemic control as 8-mm × 31-gauge and 12.7-mm × 29-gauge PNs in obese (body mass index ≥30) patients with diabetes.

Patients and Methods

This prospective, multicenter, randomized, open-label, 2-period, crossover, equivalence, home-based study was conducted from October 26, 2010, through May 31, 2012. After a 3-week wash-in period, eligible patients aged 18 to 80 years with a hemoglobin A1c (HbA1c) level of 5.5% to 9.5% (37-80 mmol/mol) were randomized to compare either 4- vs 8-mm PNs or 4- vs 12.7-mm PNs, using each of the 2 assigned PNs for 12 weeks in random order. The primary outcome was change in HbA1c level, with equivalence limits of ±0.4%.

Results

The 274 patients randomized (mean ± SD age, 56.7±11.0 years) had a mean ± SD body mass index of 37.0±6.1 (range, 29.1-59.9) and took up to 350 U of insulin daily; 226 patients were included in the modified intention-to-treat analysis. Mean (95% CI) changes in HbA1c levels with the 4-mm PN were –0.08% (–0.21 to 0.06) and –0.10% (–0.19 to 0.00) vs the 8- and 12.7-mm PNs, respectively, within equivalence margins. The 4-mm PN was less painful than the larger PNs (P<.05), with similar leakage rates reported (4.1%-4.3%). Patients preferred the 4-mm PN over the 12.7-mm PN (P<.05) but not significantly vs the 8-mm PN. There were no differences between PNs in insulin doses and hypoglycemic or hyperglycemic adverse event rates.

Conclusion

The 4-mm × 32-gauge PN provides equivalent glycemic control as 8- and 12.7-mm PNs in obese patients with diabetes, with less pain and no increase in leakage. Shorter PNs should be considered in all insulin-requiring patients with diabetes, including those who are obese.

Trial Registration

clinicaltrials.gov Identifier: NCT01231984

Section snippets

Study Design

This was a prospective, multicenter, randomized, open-label, 2-period, crossover, equivalence, home-based study. It began with a 3-week wash-in phase in which patients followed their usual insulin regimen using each of 3 PNs—4-mm × 32-gauge, 8-mm × 31-gaugue, and 12.7-mm × 29-gauge PNs (BD)—for 1 week in random order. This was done to minimize dropouts during the subsequent study by ensuring that patients were comfortable with larger PNs and found them acceptable. After the wash-in, eligible

Patient Disposition and Demographic Characteristics

Of 380 patients screened, 293 entered the 3-week wash-in period, after which 274 (94%) were randomized into the study: 139 to the 4- vs 8-mm PN arm and 135 to the 4- vs 12.7-mm PN arm. Reasons for discontinuation and study flow are outlined in Figure 1. Most discontinuations (35 of 44) occurred in period 1, with 19 patients using the 4-mm PN and 16 using the longer PNs; the most common reasons were protocol violations/noncompliance (ie, changes to treatment regimens). No discontinuations were

Discussion

In this well-controlled, prospective, randomized crossover trial, use of the shortest PN currently available (4 mm) was reported for the first time in obese patients to provide equivalent glycemic control, as measured by HbA1c levels, compared with the most commonly used PN (8 mm) and the longest PN (12.7 mm). In addition, pain ratings and other patient-reported measures generally favored the 4-mm PN vs the longer PNs, and there was no increase in skin leakage rates. The incidences of

Conclusion

The 4-mm PN provides equivalent efficacy based on HbA1c levels as 8- and 12.7-mm PNs in obese patients taking large insulin doses, with no increase in skin leakage and with favorable findings related to pain, ease of use, and overall patient preference. Shorter PNs, such as 4 mm × 32 gauge, should be considered for all patients requiring insulin delivered via pens, including those who are obese. There seems to be no basis for continued use of 12.7-mm PNs (or insulin syringes) for subcutaneous

Acknowledgments

We thank all the BD employees and study staff members who made this study possible, especially Kenneth Kassler-Taub, MD, Jane Lawrence, Michelle Koon, Catherine L. Meyers, Lucille Leopardo-Tibbetts, and Bianca Zong. Writing support was provided by Dana Franznick, PharmD, of Complete Healthcare Communications Inc (Chadds Ford, PA) under the direction of the authors, funded by BD. Editorial assistance was provided by Maryann T. Travaglini, PharmD, of Complete Healthcare Communications Inc.

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    Grant Support: Park Nicollet Institute received a research grant on behalf of Richard M. Bergenstal MD from BD (Becton Dickinson and Company, Franklin Lakes, NJ) to conduct this trial.

    Potential Competing Interests: Dr Bergenstal has served on the advisory panel for Abbott Diabetes Care, AstraZeneca/Bristol-Myers Squibb, Bayer HealthCare, Boehringer Ingelheim, Eli Lilly, Halozyme Therapeutics, Hygieia, Johnson & Johnson, Medtronic, Novo Nordisk, Roche Pharmaceuticals, and Sanofi; has served as a consultant for Abbott Diabetes Care, AstraZeneca/Bristol-Myers Squibb, Bayer HealthCare, Becton Dickinson Medical Diabetes Care, Boehringer Ingelheim, Calibra Medical, Dexcom, Eli Lilly, Halozyme Therapeutics, Hygieia, Johnson & Johnson, Medtronic, Merck, Novo Nordisk, Roche Pharmaceuticals, Sanofi, and Takeda Pharmaceuticals; has received research support from AstraZeneca, Bayer HealthCare, Becton Dickinson Diabetes Care, Boehringer Ingelheim, Calibra Medical, Dexcom, Eli Lilly, Halozyme Therapeutics, Helmsley Charitable Trust, Hygieia, Johnson & Johnson, Medtronic, Merck, Novo Nordisk, Roche Pharmaceuticals, and Sanofi; and has inherited Merck stock. All contracts are with Dr Bergenstal’s nonprofit employer, Park Nicollet Institute; Dr Bergenstal receives no personal compensation. Dr Hirsch, Mr Gibney, and Mr Parvu are employees of BD (Becton, Dickinson and Company, Inc).

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