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 - PubMed (original) (raw)

Clinical Trial

. 2015 Oct;17(10):965-73.

doi: 10.1111/dom.12498. Epub 2015 Jul 1.

Affiliations

Clinical Trial

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

S C L Gough et al. Diabetes Obes Metab. 2015 Oct.

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.

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Figures

Figure 1

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 (‐‐):

A

merican

D

iabetes

A

ssociation

HbA1c

target <7.0%;

I

nternational

D

iabetes

F

ederation

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

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

A

merican

D

iabetes

A

ssociation and

HbA1c

target ≤6.5% (48 mmol/mol) is from the

I

nternational

D

iabetes

F

ederation. (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

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.

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