The SimpleMix study with biphasic insulin aspart 30: a randomized controlled trial investigating patient-driven titration versus investigator-driven titration

Abstract

Objective:

The study aimed to confirm the efficacy, through non-inferiority, of patient-driven versus investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) in terms of glycemic control assessed by HbA1c change.

Methods:

SimpleMix was a 20 week, open-label, randomized, two-armed, parallel-group, multicenter study in five countries (Argentina, China, India, Poland, and the UK). Patients with type 2 diabetes were randomized into either patient-driven or investigator-driven BIAsp 30 titration groups.

Results:

Non-inferiority of patient-driven vs. investigator-driven titration based on change in HbA1c from baseline to week 20 could not be demonstrated. Mean (SE) estimated change from baseline to week 20 was −0.72 (0.08)% in the patient-driven group and −0.97 (0.08)% in the investigator-driven group; estimated difference 0.25% (95% CI: 0.04; 0.46). Estimated mean change (SE) in fasting plasma glucose from baseline to week 20 was similar between groups: −0.94 (0.21) mmol/L for patient-driven and −1.07 (0.22) mmol/L for investigator-driven (difference non-significant). Both treatment arms were well tolerated, and hypoglycemic episode rates were similar between groups, with a rate ratio of 0.77 (95% CI: 0.54; 1.09; p = 0.143) for all hypoglycemic episodes and 0.78 (95% CI: 0.42; 1.43; p = 0.417) for nocturnal hypoglycemic episodes.

Conclusions:

Non-inferiority of patient-driven versus investigator-driven titration with regard to change from baseline to end-of-treatment HbA1c could not be confirmed. It is possible that a clinic visit 12 weeks after intensification of treatment with BIAsp 30 in patients with type 2 diabetes inadequately treated with basal insulin may benefit patient-driven titration of BIAsp 30. A limitation of the study was the relatively small number of patients recruited in each country, which does not allow country-specific analyses to be performed. Overall, treatment with BIAsp 30 was well tolerated in both treatment groups.

Trial registration: ClinicalTrials.gov identifier: NCT01427920.

Keywords::

• Biphasic insulin aspart 30
• HbA1c
• Titration

Transparency

Declaration of funding

The study was funded by Novo Nordisk A/S, Denmark.

Declaration of financial/other relationships

Y.G., C.L. and B.S. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. H.L. and H.A. have disclosed that they are employees of and hold stock in Novo Nordisk.

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

Acknowledgments

Editorial assistance was provided by Watermeadow Medical, financed by Novo Nordisk A/S.

Previous presentations: 49th Annual European Association for the Study of Diabetes Meeting, 23–27 September 2013, Barcelona, Spain; and International Diabetes Federation, The World Diabetes Congress, 2–6 December 2013, Melbourne, Australia.

Notes

*NovoMix 30 is a registered trade name of Novo Nordisk, Bagsvaerd, Denmark