Subject-driven titration of biphasic insulin aspart 30 twice daily is non-inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open-label, parallel-group, multicenter trial

Abstract

Aims/introduction: The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID).

Materials and methods: In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group.

Results: Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively.

Conclusions: Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

Trial registration: ClinicalTrials.gov NCT01618214.

Keywords: Biphasic insulin aspart; Titration; Type 2 diabetes.

Figures

Figure 1

Subjects’ disposition.

Figure 2

Efficacy end‐points from baseline to the end of treatment. Changes of mean levels of (a) glycated hemoglobin (HbA1c), (b) fasting plasma glucose (FPG) and (c) postprandial glucose (PPG) increment with (d) last observation carried forward (full analysis set). (D) Eight‐point self‐measured plasma glucose profile at week 0 and week 20 with last observation carried forward (full analysis set); data are shown as mmol/mol (%) for HbA1c. (e) Percentages of patients achieving the HbA1c target of <7% at week 20, achieving HbA1c targets without confirmed hypoglycemic events in the last 12 months or throughout the trial (20 weeks; last observation carried forward, full analysis set). Triangle with solid line, subject‐driven group; circle with dash line, investigator‐driven group. B120, 120 min after breakfast; BB, before breakfast; BD, before dinner; BED, at bedtime; BL, before lunch; D120, 120 min after dinner; L120, 120 min after lunch.