One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial

Abstract

Aims: To confirm, in a 26-week extension study, the sustained efficacy and safety of a fixed combination of insulin degludec and liraglutide (IDegLira) compared with either insulin degludec or liraglutide alone, in patients with type 2 diabetes.

Methods: Insulin-naïve adults with type 2 diabetes randomized to once-daily IDegLira, insulin degludec or liraglutide, in addition to metformin ± pioglitazone, continued their allocated treatment in this preplanned 26-week extension of the DUAL I trial.

Results: A total of 78.8% of patients (1311/1663) continued into the extension phase. The mean glycated haemoglobin (HbA1c) concentration at 52 weeks was reduced from baseline by 1.84% (20.2 mmol/mol) for the IDegLira group, 1.40% (15.3 mmol/mol) for the insulin degludec group and 1.21% (13.2 mmol/mol) for the liraglutide group. Of the patients on IDegLira, 78% achieved an HbA1c of <7% (53 mmol/mol) versus 63% of the patients on insulin degludec and 57% of those on liraglutide. The mean fasting plasma glucose concentration at the end of the trial was similar for IDegLira (5.7 mmol/l) and insulin degludec (6.0 mmol/l), but higher for liraglutide (7.3 mmol/l). At 52 weeks, the daily insulin dose was 37% lower with IDegLira (39 units) than with insulin degludec (62 units). IDegLira was associated with a significantly greater decrease in body weight (estimated treatment difference, -2.80 kg, p < 0.0001) and a 37% lower rate of hypoglycaemia compared with insulin degludec. Overall, all treatments were well tolerated and no new adverse events or tolerability issues were observed for IDegLira.

Conclusions: These 12-month data, derived from a 26-week extension of the DUAL I trial, confirm the initial 26-week main phase results and the sustainability of the benefits of IDegLira compared with its components in glycaemic efficacy, safety and tolerability.

Keywords: diabetes therapy; hypoglycaemia; insulin degludec; liraglutide.

© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

(A) Mean glycated haemoglobin (HbA1c) concentration over time, by treatment group. Mean values with error bars [standard error of the mean (s.e.m.)] based on the full analysis set (FAS) and LOCF‐imputed data. p values from an analysis of covariance (ancova) model. Dashed lines (‐‐): American Diabetes Association HbA1c target <7.0%; International Diabetes Federation HbA1c target ≤6.5%. (B) Mean daily doses of insulin degludec and liraglutide components of treatment, over time. Mean values with error bars (s.e.m.) based on safety analysis set and LOCF‐imputed data; n for each treatment based on FAS; week 52 dose is observed dose based on FAS. (C) Change in mean body weight over time, by treatment group. Mean values with error bars (s.e.m.) based on FAS and LOCF‐imputed data. Estimated treatment differences and p values are from an ancova model. EOT, end of trial; IDeg, insulin degludec; IDegLira, insulin degludec/liraglutide combination; Lira, liraglutide. Results at 26 weeks are from the main phase of the DUAL I trial and have been reported previously 5).

Figure 2

(A) Percentage of subjects reaching a glycated haemoglobin (HbA1c) target of <7.0 or ≤6.5% at 26 and 52 weeks, by treatment group. Values based on full analysis set (FAS) and LOCF‐imputed data; p values are from a logistic regression model. HbA1c target <7.0% (53 mmol/mol) is from American Diabetes Association and HbA1c target ≤6.5% (48 mmol/mol) is from the International Diabetes Federation. (B) HbA1c reduction at 52 weeks by treatment group, stratified by baseline BMI. Data are mean from observed values based on FAS and LOCF‐imputed data; p values from ancova model. n, number of subjects contributing to the analysis. IDeg, insulin degludec; IDegLira, insulin degludec/liraglutide combination; Lira, liraglutide. Results at 26 weeks are from the main phase of the DUAL I trial and have been reported previously 5.

Figure 3

Fasting plasma glucose (FPG) from 0 to 52 weeks by treatment group. Mean values with error bars (standard error of the mean) based on full analysis set and LOCF‐imputed data; p value is from an analysis of covariance model. IDeg, insulin degludec; IDegLira, insulin degludec/liraglutide combination; Lira, liraglutide. Results at 26 weeks are from the main phase of the DUAL I trial and have been reported previously 5.