Insulin degludec/liraglutide (IDegLira) maintains glycaemic control and improves clinical outcomes, regardless of pre-trial insulin dose, in people with type 2 diabetes that is uncontrolled on basal insulin

L Meneghini, A Doshi, D Gouet, T Vilsbøll, K Begtrup, P Őrsy, M F Ranthe, I Lingvay, L Meneghini, A Doshi, D Gouet, T Vilsbøll, K Begtrup, P Őrsy, M F Ranthe, I Lingvay

Abstract

Aims: To assess whether people with type 2 diabetes transferring from higher basal insulin doses (> 20 units) to a starting dose of 16 units of insulin degludec/liraglutide (IDegLira) benefit from IDegLira with/without transient loss of glycaemic control.

Methods: Post hoc analysis of DUAL V and VII assessed fasting self-measured blood glucose (SMBG) over weeks 1-8, changes in HbA1c, body weight and mean insulin dose over 26 weeks, and percentage of participants achieving HbA1c < 53 mmol/mol (7.0%) by end of trial in participants with type 2 diabetes uncontrolled with basal insulin. IDegLira was compared with continued up-titration of insulin glargine (IGlar U100) in DUAL V, or switching to basal-bolus therapy in DUAL VII (IGlar U100 and insulin aspart), across pre-trial insulin dose groups (20-29, 30-39 and 40-50 units/day).

Results: In all subgroups, participants treated with IDegLira experienced significant improvements in HbA1c by end of trial, which were greater than with IGlar U100 up-titration (estimated treatment difference -5.86, -6.59 and -6.91 mmol/mol for pre-trial insulin doses of 20-29, 30-39 and 40-50 units/day, respectively) and similar to basal-bolus therapy (estimated treatment difference -0.16, -1.0 and -0.01 mmol/mol for pre-trial insulin doses of 20-29, 30-39 and 40-50 units/day, respectively). Compared with IGlar U100 and basal-bolus therapy, IDegLira participants experienced weight loss vs. weight gain, lower rates of hypoglycaemia and a lower mean end of trial total daily insulin dose. In both trials, mean fasting SMBG decreased from weeks 1 to 8 across all subgroups, despite a temporary increase in mean fasting SMBG in the 40-50 units pre-trial insulin dose group during week 1 [mean increase (sd) +1.1 (2.0) mmol/l for DUAL V and +1.1 (2.1) mmol/l for DUAL VII], which reverted to baseline by week 4.

Conclusions: Regardless of pre-trial insulin dose, IDegLira resulted in improved clinical outcomes, even in participants transferring from 40-50 units of basal insulin, despite a transient (< 4 weeks), clinically non-relevant, elevation in pre-breakfast SMBG. (Clinical Trial Registry Number NCT01952145 and NCT02420262).

© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Figures

Figure 1
Figure 1
Change in HbA1c by pre‐trial insulin dose group in the (a) DUAL V and (b) DUAL VII trials. Data are observed means based on the full analysis set using either last observation carried forward imputed data for DUAL V or observed data with no imputation for DUAL VII. In DUAL V, change in HbA1c was analysed using an analysis of covariance (ANCOVA) model (including the variables: subgroup, treatment, interaction between subgroup and treatment and region as fixed factors and baseline response as covariates). In DUAL VII, the mixed model of repeated measures (MMRM) included subgroup, treatment, visit and region as fixed factors and baseline response as covariate and the interactions subgroup × treatment × visit, region × visit, baseline response × visit. Mean value (± SEM) at EOT. *P ≤ 0.0001. N† is the number of participants with a recorded absolute change in HbA1c. There was no significant interaction between pre‐trial insulin dose groups and treatment arm in either the DUAL V (P = 0.85) or DUAL VII (P = 0.86) trials in HbA1c from baseline to end of trial. EOT, end of trial; ETD, estimated treatment difference (with 95% confidence intervals); IAsp, insulin aspart; IDegLira, insulin degludec/liraglutide; IGlar U100, insulin glargine 100 units/ml.
Figure 2
Figure 2
Percentage of participants reaching HbA1c < 53 mmol/mol (7.0%) at end of trial in the (a) DUAL V and (b) DUAL VII trials. Data are percentages based on the full analysis set using either observed data with last observation carried forward imputed data for DUAL V or observed data with no imputation for DUAL VII. IAsp, insulin aspart; IDegLira, insulin degludec/liraglutide; IGlar U100, insulin glargine 100 units/ml.
Figure 3
Figure 3
Fasting SMBG by pre‐trial insulin dose group in the first 8 weeks. Participants in the (a) DUAL V and (b) DUAL VII trials receiving 20–29 units/day; participants in the (c) DUAL V and (d) DUAL VII trials receiving 30–39 units/day; participants in the (e) DUAL V and (f) DUAL VII trials receiving 40–50 units/day. Data are based on the full analysis set using either observed data with last observation carried forward imputed data for DUAL V or observed data with no imputation for DUAL VII. IAsp, insulin aspart; IDegLira, insulin degludec/liraglutide; IGlar U100, insulin glargine 100 units/ml; SMBG, self‐measured blood glucose.
Figure 4
Figure 4
Total actual daily insulin dose over time by pre‐trial insulin dose group. Participants in the (a) DUAL V and (b) DUAL VII trials receiving 20–29 units/day; participants in the (c) DUAL V and (d) DUAL VII trials receiving 30–39 units/day; participants in the (e) DUAL V and (f) DUAL VII trials receiving 40–50 units/day. Data are observed data based on the full analysis set using either last observation carried forward imputed data for DUAL V or observed data with no imputation for DUAL VII. IAsp, insulin aspart; IDegLira, insulin degludec/liraglutide; IGlar U100, insulin glargine 100 units/ml.
Figure 5
Figure 5
Change in body weight by pre‐trial insulin dose group in the (a) DUAL V and (b) DUAL VII trials. Data are observed means based on the full analysis set using either last observation carried forward imputed data for DUAL V or observed data with no imputation for DUAL VII. In DUAL V, change in body weight was analysed using an analysis of covariance (ANCOVA) model (including the variables: subgroup, treatment, interaction between subgroup and treatment and region as fixed factors and baseline response as covariates). In DUAL VII, the mixed model of repeated measures (MMRM) included subgroup, treatment, visit and region as fixed factors and baseline response as covariate and the interactions subgroup × treatment × visit, region × visit, baseline response × visit. *P ≤ 0.0001. There was no significant interaction between pre‐trial insulin dose groups and treatment arm in the DUAL V (P = 0.17) trial; however, there was a significant interaction in DUAL VII (P = 0.03) in participants’ body weight. ETD, ETD, estimated treatment difference; IAsp, insulin aspart; IDegLira, insulin degludec/liraglutide; IGlar U100, insulin glargine 100 units/ml.

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