The effect of basal-bolus therapy varies with baseline 1,5-anhydroglucitol level in people with Type 2 diabetes: a post hoc analysis

Abstract

Aims: To investigate the impact of baseline 1,5-anhydroglucitol on the treatment effect of basal-bolus therapy in people with Type 2 diabetes.

Methods: Post hoc analysis of onset 3, an 18-week, randomized, phase 3 trial evaluating the efficacy and safety of fast-acting insulin aspart in basal-bolus therapy (n = 116) vs. basal insulin-only therapy (n = 120) in people with Type 2 diabetes. The estimated treatment difference in change from baseline in HbA1c was investigated for different cut-off values of baseline 1,5-anhydroglucitol (2, 3, 4, 5 and 6 μg/ml).

Results: The estimated treatment difference in change from baseline in HbA1c between basal-bolus therapy and basal insulin-only therapy was statistically significantly greater in participants with baseline 1,5-anhydroglucitol ≤3 μg/ml (n = 34) vs. >3 μg/ml (n = 198) [estimated treatment difference (95% CI): -1.53% (-2.12; -0.94) vs. -0.82% (-1.07; -0.57); P-value for interaction = 0.03]. The estimated treatment difference became more pronounced when comparing participants with 1,5-anhydroglucitol ≤2 μg/ml (n = 15) vs. >2 μg/ml (n = 217) [estimated treatment difference (95% CI): -2.26% (-3.15; -1.36) vs. -0.85% (-1.08; -0.62); P-value for interaction = 0.003]. For cut-off values ≥4 μg/ml, estimated treatment differences were numerically greater below the cut-off compared with above, although the interaction terms were not statistically significant.

Conclusion: This analysis indicates that people with Type 2 diabetes with low 1,5-anhydroglucitol have an added treatment benefit with basal-bolus therapy compared with people with higher 1,5-anhydroglucitol. Further research is needed to clarify any clinical utility of these findings. Clinical Trials Registry No: NCT01850615.

© 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Figures

Figure 1

Scatter plot of change from baseline in HbA1c after 18 weeks of randomized treatment against baseline 1,5‐AG. Penalized B‐spline scatter plot smoothing is used to depict the association between change from baseline in HbA1c and baseline 1,5‐AG. 1,5‐AG, 1,5‐anhydroglucitol; faster aspart, fast‐acting insulin aspart.

Figure 2

Estimated treatment difference in change from baseline in HbA1c above and below different 1,5‐AG cut‐off values. Change from baseline in HbA1c was analysed using an MMRM. The model included a treatment‐by‐subgroup interaction, alongside main effects of treatment, subgroup (above/below cut‐off value), region and strata, with baseline HbA1c and baseline 1,5‐AG as covariates. P‐values for the interaction term were used to evaluate if the ETD was different above vs. below the cut‐off values. Only participants with post‐baseline HbA1c data contributed to the MMRM analysis (n = 232). 1,5‐AG, 1,5‐anhydroglucitol; CI, confidence interval; ETD, estimated treatment difference; MMRM, mixed‐effects model for repeated measures; n, number of participants contributing to the analysis.