Efficacy and safety of biphasic insulin aspart 70/30 in type 2 diabetes patients of different race or ethnicity (INITIATEplus trial)

Abstract

Objective:

To determine if self-titration using biphasic insulin aspart 70/30 (BIAsp 30) had a different impact on efficacy and safety across different racial/ethnic subgroups.

Research design/methods:

This was an exploratory, post hoc analysis by race (White vs. Black/African-American) and ethnicity (Hispanic/Latino vs. non-Hispanic/Latino) of data from the INITIATEplus trial. Participants were treated twice-daily with BIAsp 30 over 24 weeks.

Trial registration:

ClinicalTrials.gov identifier: NCT00101751.

Main outcome measures:

Efficacy endpoints included reductions in mean glycated hemoglobin (A1C) and fasting plasma glucose (FPG). Safety endpoints included hypoglycemia rates (events/patient-year) and adverse events. Body weight changes were also measured.

Results:

Glycemic control improved by a similar extent for all demographic groups. Observed mean decreases in A1C ranged from 2.4% to 2.6% after 24 weeks’ treatment. Baseline-adjusted mean A1C decreases for White vs. Black/African-American subjects were 2.56% and 2.13% (p < 0.0001), and for Hispanic/Latino vs. non-Hispanic/Latino subjects were 2.45% and 2.42% (p = 0.677), respectively. Final FPG values were similar among all groups (141–146 mg/dL [7.83–8.10 m mol/L]), and baseline-adjusted FPG decreases were not significantly different (p > 0.025) between groups. Hypoglycemia was low for White, Black/African-American, Hispanic/Latino, and non-Hispanic/Latino subjects (0.08, 0.04, 0.03, and 0.07 major events/patient-year, with 0.60, 0.30, 0.37, and 0.52 minor events/patient-year, respectively). Body weight increases were 3.17 and 3.06 kg (White vs. African-American) and 2.69 and 3.19 kg (Hispanic/Latino vs. non-Hispanic/Latino). Final weight-adjusted total daily insulin doses were 0.60U/kg for Black/African-American subjects vs. 0.78U/kg for White subjects (p < 0.0001), and 0.71U/kg for Hispanic/Latino subjects vs. 0.74U/kg for non-Hispanic/Latino subjects (p = 0.42).

Limitations:

The trial was not designed or powered for comparisons across racial or ethnic groups, subjects were not stratified for pre-baseline medication regimens between each race and ethnic group, and unequal subject numbers and baseline A1C disparities existed between the pairs of groups being compared.

Conclusions:

Diabetes self-management with BIAsp 30 using an easily followed self-titration algorithm produced low hypoglycemia rates. All subgroups achieved A1C reductions >2.1% and FPG declines >82 mg/dL that were similar across groups, demonstrating that self-titration of BIAsp 30 can successfully be pursued in a primary care setting by patients who had previously failed to meet ADA A1C targets under oral antidiabetes therapy, with race or ethnicity not an obstacle to achieving better glycemic control.

Keywords::

• BIAsp 30
• Biphasic insulin aspart 70/30
• Ethnicity
• Glucose control
• INITIATEplus
• NovoLog Mix 70/30
• Race
• Self-titration
• Type 2 diabetes

Transparency

Declaration of funding

Funding to support this study and the preparation of this manuscript was provided by Novo Nordisk Inc. Novo Nordisk provided clinical trial supplies, monitored the trial, performed the statistical analyses, and prepared the clinical trial report. The authors had full access to the data and take responsibility for the accuracy of the data and its analysis.

Author contributions: B.S.T., M.D.S., F.C.C., and A.B. conducted the research, contributed to discussions, and helped write, review, and revise the manuscript. J.B. and D.S.O. conducted the research, analyzed data, contributed to discussions, and helped write, review, and revise the manuscript. P-L.C. performed the statistical analyses, and helped review and revise the manuscript. The paper was prepared according to the ICMJE’s Uniform Requirements for Manuscripts Submitted to Biomedical Journals and the International Society for Medical Publication Professionals’ ‘Good Publication Practice for Communicating Company-Sponsored Medical Research: The GPP2 Guidelines.’

Declaration of financial/other relationships

B.S.T. has been a Novo Nordisk speakers’ bureau member and has received grant support from Novo Nordisk for clinical research. M.D.S. is affiliated with Novo Nordisk as a consultant, national speaker, researcher, recipient of grant support, and owns Novo Nordisk stock. F.C.C. has been a Novo Nordisk speakers’ bureau member and is a Novo Nordisk advisory board member. A.B. is a Novo Nordisk speakers’ bureau member and has received grant support from Novo Nordisk for clinical research. D.S.O. is a Novo Nordisk speakers’ bureau and advisory board member. J.B. and P-L.C. are employees of Novo Nordisk and own Novo Nordisk stock.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors acknowledge medical writing assistance from Dr Edward. S. Kimball of Novo Nordisk, who provided the authors with a first draft based on discussions, and also wish to thank MedVal Scientific Information Services, LLC for editorial assistance in preparing the manuscript for publication. The authors also gratefully acknowledge the participation of the members of the INITIATEplus Study Group.

Data from this study were presented at the American Diabetes Association 67th Scientific Sessions, June 22–26, 2007, Chicago, Illinois, USA.