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Insulin Degludec Once-Daily in Type 2 Diabetes: Simple or Step-Wise Titration (BEGIN: Once Simple Use)

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Abstract

Introduction

Insulin degludec (IDeg) is a new basal insulin in development with a flat, ultra-long action profile that may permit dosing using a simplified titration algorithm with less frequent self-measured blood glucose (SMBG) measurements and more simplified titration steps than currently available basal insulins.

Methods

This 26-week, multi-center, open-label, randomized, treat-to-target study compared the efficacy and safety of IDeg administered once-daily in combination with metformin in insulin-naïve subjects with type 2 diabetes using two different patient-driven titration algorithms: a “Simple” algorithm, with dose adjustments based on one pre-breakfast SMBG measurement (n = 111) versus a “Step-wise” algorithm, with adjustments based on three consecutive pre-breakfast SMBG values (n = 111). IDeg was administered using the FlexTouch® insulin pen (Novo Nordisk A/S, Bagsværd, Denmark), with once-weekly dose titration in both groups.

Results

Glycosylated hemoglobin (HbA1c) decreased from baseline to week 26 in both groups (−1.09%, IDegSimple; −0.93%, IDegStep-wise). IDegSimple was non-inferior to IDegStep-wise in lowering HbA1c [estimated treatment difference (IDegSimple − IDegStep-wise): −0.16% points (−0.39; 0.07)95% CI]. Fasting plasma glucose was reduced (−3.27 mmol/L, IDegSimple; −2.68 mmol/L, IDegStep-wise) with no significant difference between groups. Rates of confirmed hypoglycemia [1.60, IDegSimple; 1.17, IDegStep-wise events/patient year of exposure (PYE)] and nocturnal confirmed hypoglycemia (0.21, IDegSimple; 0.10, IDegStep-wise events/PYE) were low, with no significant differences between groups. Daily insulin dose after 26 weeks was 0.61 U/kg (IDegSimple) and 0.50 U/kg (IDegStep-wise). No significant difference in weight change was seen between groups by week 26 (+1.6 kg, IDegSimple; +1.1 kg, IDegStep-wise), and there were no clinically relevant differences in adverse event profiles.

Conclusion

IDeg was effective and well tolerated using either the Simple or Step-wise titration algorithm. While selection of an algorithm must be based on individual patient characteristics and goals, the ability to attain good glycemic control using a simplified titration algorithm may enable patient empowerment through self-titration, improved convenience, and reduced costs.

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Acknowledgments

The study and article publication charge were sponsored by Novo Nordisk A/S (Bagsværd, Denmark). The authors thank the investigators, trial staff, and participants for their participation. The authors also thank Lisa Bonk, PharmD, MBA and Carolynne Van Houten, employees of Novo Nordisk, Inc., Princeton, NJ, USA, for providing medical writing and editorial assistance, and colleagues at Watermeadow Medical (sponsored by Novo Nordisk A/S) for copy editing, preparation of artwork, and submission assistance.

This full article has not been previously published nor is it currently submitted for consideration for publication elsewhere.

All authors contributed to design, conduct/data collection, analysis and interpretation of data and to the writing and final approval of this article.

Dr. Philis-Tsimikas is the guarantor for this article, and takes responsibility for the integrity of the work as a whole.

List of investigators

Finland: Arto Kuusisto, Vesa Järveläinen; Liisa Sorakivi, Sakari Sulosaari, Anne-Mari Helkkula; Germany: Thomas Behnke, Ralf Jordan, Karsten Milek, Rainer Paulus, Ludger Rose, Armin Sammler; Spain: Pedro Mezquita, Miguel Ángel Garcia, Santiago Tofé, Josefina Olivares, Esteban Jódar, Francisco Tinahones; USA: Alexander Murray, Marcus Merriweather, Dave Webster, Gary Bedel, Ileana Tandron, Jack Wahlen, Jeffrey Rothman, Jonathan Liss, Joshua Frame, Justen Rudolph, Michael Cooperman, Mohammed Bari, Norman Soler, Raul Gaona, Hubert Reyes and Steven Elliott, Elise Kwon, Teresa Sligh, Rakesh Patel, Ronald Gilman, Lon Lynn, David Deatkine, Athena Philis-Tsimikas, Joseph Risser, Peter Winkle, Saadat Ansari, Richard L. Murphy.

Conflict of interest

Athena Philis-Tsimikas has attended advisory boards for Novo Nordisk, Sanofi-Aventis and Merck and received research/education support from Takeda, Sankyo, Merck, Novo Nordisk, Sanofi-Aventis, Lilly, Amylin, Astra Zeneca and Pfizer. Meryl Brod has acted as a consultant to Forest Laboratories, Abbvie, Merck, Genentech and Novo Nordisk. Marcus Niemeyer is an employee of Novo Nordisk. Ann Marie Ocampo Francisco is an employee of Novo Nordisk and holds stock in the company. Jeffrey Rothman has received clinical trials support from Amylin (now Bristol-Myers-Squibb), Boehringer-Ingelheim, Intarcia, GSK, Merck, Novo Nordisk, NPS Pharmaceuticals, and Sanofi-Aventis; attended speakers’ bureaus for Boehringer-Ingelheim, Bristol-Myers-Squibb, Lilly, Sanofi-Aventis, Takeda; and acted as a consultant for NPS Pharmaceuticals, Takeda and Novo Nordisk.

Compliance with ethics guidelines

The study was conducted according to the Helsinki Declaration of 1975, as revised in 2000 and 2008 and ICH Good Clinical Practice (1996) guidelines, with prior approval by appropriate ethics committees and patient consent obtained in writing prior to the start of any study-related activities.

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Authors and Affiliations

  1. Scripps Whittier Diabetes Institute, 9894 Genesee Ave, La Jolla, CA, 92037, USA

    Athena Philis-Tsimikas

  2. The Brod Group, 219 Julia Ave, Mill Valley, CA, 94941, USA

    Meryl Brod

  3. Novo Nordisk A/S, Søborg, Denmark

    Marcus Niemeyer & Ann Marie Ocampo Francisco

  4. University Physicians Group-Research Division, 1460 Victory Blvd, Staten Island, NY, 10301, USA

    Jeffrey Rothman

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  1. Athena Philis-Tsimikas
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  2. Meryl Brod
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  5. Jeffrey Rothman
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Corresponding author

Correspondence to Athena Philis-Tsimikas.

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ClinicalTrials.gov #NCT01326026.

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Philis-Tsimikas, A., Brod, M., Niemeyer, M. et al. Insulin Degludec Once-Daily in Type 2 Diabetes: Simple or Step-Wise Titration (BEGIN: Once Simple Use). Adv Ther 30, 607–622 (2013). https://doi.org/10.1007/s12325-013-0036-1

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