Efficacy and safety of the fixed-ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type 2 diabetes: A subgroup analysis of two phase III trials

Abstract

Aims/introduction: To assess efficacy and safety of insulin degludec/liraglutide (IDegLira) in Japanese participants with type 2 diabetes across different baseline characteristics.

Materials and methods: Data from two randomized controlled trials were used: DUAL I Japan (n = 819 insulin-naïve participants) and DUAL II Japan (n = 210 insulin-experienced participants). Outcomes were assessed according to baseline glycated hemoglobin ( HbA_1c ; <8.0%, ≥8.0-<9.0%, ≥9.0%), body mass index (<25, ≥25-<30, ≥30 kg/m² ) and age (<65, ≥65 years).

Results: In DUAL I Japan, reductions in HbA_1c with IDegLira versus degludec and liraglutide were observed across all subgroups (treatment differences: -0.48% to -0.72% vs degludec, -0.29% to -0.73% vs liraglutide). Results were similar with IDegLira versus degludec in DUAL II Japan (treatment differences: -0.82% to -1.61%). Treatment-by-subgroup interactions were significant for IDegLira versus liraglutide for baseline HbA_1c and age in DUAL I Japan, and for IDegLira versus degludec for baseline HbA_1c in DUAL II Japan. In DUAL I Japan, IDegLira was associated with less weight gain than degludec in most subgroups. In DUAL II Japan, IDegLira was associated with a small mean weight loss (except for baseline HbA_1c ≥9.0%) versus a small gain for degludec (except for age ≥65 years subgroup); treatment-by-subgroup interactions were not significant. Total daily insulin dose was lower with IDegLira versus degludec across all categories, except for age >65 years in DUAL II Japan.

Conclusions: IDegLira reduced HbA_1c in Japanese participants with type 2 diabetes across baseline HbA_1c , body mass index and age categories, without unexpected safety issues.

Keywords: Insulin degludec/liraglutide; Japan; Type 2 diabetes mellitus.

Figure 1

Change in glycated hemoglobin (HbA_1c) with insulin degludec/liraglutide (IDegLira), degludec and liraglutide according to (a,b) baseline glycated hemoglobin (HbA_1c), (c,d) baseline body mass index (BMI) and (e,f) age in DUAL I Japan and DUAL II Japan. Points represent the observed mean HbA_1c at baseline and the arrows represent the observed mean HbA_1c at end‐of‐trial. Changes from baseline in HbA_1c were analyzed using an analysis of covariance (ancova) model, which included treatment, pre‐trial diabetes treatment, subgroup (baseline HbA_1c, BMI or age), and interaction between treatment and subgroup as fixed factors. For analysis of change in HbA_1c, baseline HbA1c was included as a covariate. Missing data were imputed using last observation carried forward. From the model, treatment differences with 95% confidence intervals (95% CI) were estimated for each subgroup, and the treatment‐by‐subgroup interaction was tested to assess if the treatment effect was affected by the subgroups. ETD, estimated treatment difference.

Figure 2

Change in bodyweight with insulin degludec/liraglutide (IDegLira), degludec and liraglutide according to (a,b) baseline glycated hemoglobin (HbA_1c), (c,d) baseline body mass index (BMI) and (e,f) age in DUAL I Japan and DUAL II Japan. Bars represent the observed mean change from baseline to end‐of‐trial (EOT) in bodyweight. Changes from baseline in bodyweight were analyzed using an analysis of covariance (ancova) model, which included treatment, pre‐trial diabetes treatment, subgroup (baseline HbA_1c, BMI or age), and interaction between treatment and subgroup as fixed factors. For analysis of change in bodyweight, baseline bodyweight was included as a covariate. Missing data were imputed using last observation carried forward. From the model, treatment differences with 95% confidence intervals (95% CI) were estimated for each subgroup, and the treatment‐by‐subgroup interaction was tested to assess if the treatment effect was affected by the subgroups. ETD, estimated treatment difference.

Figure 3

End‐of‐trial (EOT) daily total insulin dose in insulin degludec/liraglutide (IDegLira)‐ and degludec‐treated participants according to (a,b) baseline glycated hemoglobin (HbA_1c), (c,d) baseline body mass index (BMI) and (e,f) age in DUAL I Japan and DUAL II Japan. Bars represent the observed mean EOT daily total insulin dose. EOT total daily insulin dose was analyzed using an analysis of covariance (ancova) model, which included treatment, pre‐trial diabetes treatment, subgroup (baseline HbA_1c, BMI or age), and interaction between treatment and subgroup as fixed factors. Baseline HbA_1c (both trials) and baseline insulin dose (DUAL II Japan only) were included as covariate(s). Missing data were imputed using last observation carried forward. From the model, treatment differences with 95% confidence intervals (95% CI) were estimated for each subgroup, and the treatment‐by‐subgroup interaction was tested to assess if the treatment effect was affected by the subgroups. ETD, estimated treatment difference.