Baseline nocturnal glucose change: A predictor of the treatment effect of bolus intensification in insulin-treated type 2 diabetes

Abstract

This post hoc analysis of an 18-week randomized trial explored the utility of calculating baseline glycated haemoglobin (HbA1c), postprandial glucose (PPG) increments and nocturnal glucose change in predicting efficacy and safety outcomes in response to bolus insulin intensification in people with type 2 diabetes (T2D). Analyses were conducted on 236 participants with T2D receiving metformin: 116 received fast-acting insulin aspart (faster aspart) basal-bolus therapy and 120 received basal-only insulin. Participants were grouped according to baseline HbA1c, PPG increments and nocturnal glucose change variables; analyses were performed on the end-of-trial treatment differences between "high" and "low" baseline values. The change from baseline in end-of-trial mean HbA1c and mean PPG increments was in favour of faster aspart across all subgroups. Significantly greater treatment differences were observed in participants with high (vs. low) baseline nocturnal glucose change and PPG increments. For baseline HbA1c, significantly greater treatment differences were observed for change in end-of-trial PPG increments, but not end-of-trial HbA1c. In conclusion, both nocturnal glucose change and PPG increments may be more useful than HbA1c for identifying subgroups of people with T2D who would most benefit from bolus intensification.

Keywords: clinical trial; insulin therapy; randomized trial; type 2 diabetes.

Conflict of interest statement

A.L.P. has served on advisory boards for Abbott Diabetes Care, Becton Dickinson, Bigfoot, Eli Lilly and Company, Lexicon, Livongo, Mannkind, Medscape, Merck, Novo Nordisk, Omada Health, Sanofi and Zafgen, has served on a speakers' bureau for Novo Nordisk and received research funding from AstraZeneca, Dexcom and Mannkind. M.P. has participated in advisory panels for Novo Nordisk, Boehringer Ingelheim and Eli Lilly. J.E. is an employee of and holds stock in Novo Nordisk. K.S.‐S. is an employee of and holds shares in Novo Nordisk. J.S. is an employee of and holds stock in Novo Nordisk. K.B. has participated in advisory panels for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Sanofi, Johnson & Johnson, and speakers' bureau for Novo Nordisk and Sanofi.

© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

Change from baseline in glycated haemoglobin (HbA1c) at week 18, stratified by baseline variables. *Negative values are in favour of fast‐acting insulin aspart (faster aspart). **Statistically significant difference between estimated treatment difference (ETD) reported in the “high” and “low” subgroups. CI, confidence interval; PPG, postprandial glucose

Figure 2

Change from baseline in mean postprandial glucose (PPG) increment at week 18, stratified by baseline variables. *Negative values are in favour of fast‐acting insulin aspart (faster aspart). **Statistically significant difference between estimated treatment difference (ETD) reported in “high” and “low” subgroups. CI, confidence interval; HbA1c, glycated haemoglobin