Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide: a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study)

V. R. Aroda, T. S. Bailey, B. Cariou, S. Kumar, L. A. Leiter, Philip Raskin, J. Zacho, T. H. Andersen, A. Philis-Tsimikas

Research output: Contribution to journalArticle

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Abstract

Aim: To evaluate the efficacy and safety of adding insulin degludec (IDeg) to treatment in patients with type 2 diabetes receiving liraglutide and metformin and qualifying for treatment intensification because of inadequate glycaemic control. Methods: In this 26-week, double-blind trial, patients who still had inadequate glycaemic control after a 15-week run-in period with initiation and dose escalation of liraglutide to 1.8 mg in combination with metformin (≥1500 mg) were randomized to addition of once-daily IDeg (‘IDeg add-on to liraglutide’ arm; n = 174) or placebo (‘placebo add-on to liraglutide’ arm; n = 172), with dosing of both IDeg and placebo based on titration guidelines. Results: At 26 weeks, the mean change in glycated haemoglobin level was greater in the IDeg add-on to liraglutide arm (−1.04%) than in the placebo add-on to liraglutide arm (−0.16%; p <0.0001). Similarly, the mean fasting plasma glucose reduction was greater, and self-measured plasma glucose values were lower at all eight time points, with IDeg add-on versus placebo add-on (both p <0.0001). At 26 weeks, the IDeg dose was 51 U (0.54 U/kg). During the run-in period with liraglutide, body weight decreased by ∼3 kg in both groups. After 26 weeks, the mean change was +2.0 kg (IDeg add-on to liraglutide) and −1.3 kg (placebo add-on to liraglutide). Confirmed hypoglycaemia rates were low in both groups, although higher with IDeg than with placebo (0.57 vs. 0.12 episodes/patient-years of exposure; p = 0.0002). Nocturnal confirmed hypoglycaemia was infrequent in both groups, with no episodes of severe hypoglycaemia, and no marked differences in adverse events with either treatment approach. Conclusion: The addition of liraglutide and IDeg to patients sub-optimally treated with metformin and liraglutide and requiring treatment intensification was found to be effective and well-tolerated.

Original languageEnglish (US)
Pages (from-to)663-670
Number of pages8
JournalDiabetes, Obesity and Metabolism
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2016

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Glucagon-Like Peptide 1
Metformin
Type 2 Diabetes Mellitus
Randomized Controlled Trials
Placebos
Hypoglycemia
Therapeutics
insulin degludec
Liraglutide
Glucose
Glycosylated Hemoglobin A
Fasting
Body Weight
Guidelines

Keywords

  • GLP-1
  • glycaemic control
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide : a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study). / Aroda, V. R.; Bailey, T. S.; Cariou, B.; Kumar, S.; Leiter, L. A.; Raskin, Philip; Zacho, J.; Andersen, T. H.; Philis-Tsimikas, A.

In: Diabetes, Obesity and Metabolism, Vol. 18, No. 7, 01.07.2016, p. 663-670.

Research output: Contribution to journalArticle

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abstract = "Aim: To evaluate the efficacy and safety of adding insulin degludec (IDeg) to treatment in patients with type 2 diabetes receiving liraglutide and metformin and qualifying for treatment intensification because of inadequate glycaemic control. Methods: In this 26-week, double-blind trial, patients who still had inadequate glycaemic control after a 15-week run-in period with initiation and dose escalation of liraglutide to 1.8 mg in combination with metformin (≥1500 mg) were randomized to addition of once-daily IDeg (‘IDeg add-on to liraglutide’ arm; n = 174) or placebo (‘placebo add-on to liraglutide’ arm; n = 172), with dosing of both IDeg and placebo based on titration guidelines. Results: At 26 weeks, the mean change in glycated haemoglobin level was greater in the IDeg add-on to liraglutide arm (−1.04{\%}) than in the placebo add-on to liraglutide arm (−0.16{\%}; p <0.0001). Similarly, the mean fasting plasma glucose reduction was greater, and self-measured plasma glucose values were lower at all eight time points, with IDeg add-on versus placebo add-on (both p <0.0001). At 26 weeks, the IDeg dose was 51 U (0.54 U/kg). During the run-in period with liraglutide, body weight decreased by ∼3 kg in both groups. After 26 weeks, the mean change was +2.0 kg (IDeg add-on to liraglutide) and −1.3 kg (placebo add-on to liraglutide). Confirmed hypoglycaemia rates were low in both groups, although higher with IDeg than with placebo (0.57 vs. 0.12 episodes/patient-years of exposure; p = 0.0002). Nocturnal confirmed hypoglycaemia was infrequent in both groups, with no episodes of severe hypoglycaemia, and no marked differences in adverse events with either treatment approach. Conclusion: The addition of liraglutide and IDeg to patients sub-optimally treated with metformin and liraglutide and requiring treatment intensification was found to be effective and well-tolerated.",
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T1 - Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide

T2 - a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study)

AU - Aroda, V. R.

AU - Bailey, T. S.

AU - Cariou, B.

AU - Kumar, S.

AU - Leiter, L. A.

AU - Raskin, Philip

AU - Zacho, J.

AU - Andersen, T. H.

AU - Philis-Tsimikas, A.

PY - 2016/7/1

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N2 - Aim: To evaluate the efficacy and safety of adding insulin degludec (IDeg) to treatment in patients with type 2 diabetes receiving liraglutide and metformin and qualifying for treatment intensification because of inadequate glycaemic control. Methods: In this 26-week, double-blind trial, patients who still had inadequate glycaemic control after a 15-week run-in period with initiation and dose escalation of liraglutide to 1.8 mg in combination with metformin (≥1500 mg) were randomized to addition of once-daily IDeg (‘IDeg add-on to liraglutide’ arm; n = 174) or placebo (‘placebo add-on to liraglutide’ arm; n = 172), with dosing of both IDeg and placebo based on titration guidelines. Results: At 26 weeks, the mean change in glycated haemoglobin level was greater in the IDeg add-on to liraglutide arm (−1.04%) than in the placebo add-on to liraglutide arm (−0.16%; p <0.0001). Similarly, the mean fasting plasma glucose reduction was greater, and self-measured plasma glucose values were lower at all eight time points, with IDeg add-on versus placebo add-on (both p <0.0001). At 26 weeks, the IDeg dose was 51 U (0.54 U/kg). During the run-in period with liraglutide, body weight decreased by ∼3 kg in both groups. After 26 weeks, the mean change was +2.0 kg (IDeg add-on to liraglutide) and −1.3 kg (placebo add-on to liraglutide). Confirmed hypoglycaemia rates were low in both groups, although higher with IDeg than with placebo (0.57 vs. 0.12 episodes/patient-years of exposure; p = 0.0002). Nocturnal confirmed hypoglycaemia was infrequent in both groups, with no episodes of severe hypoglycaemia, and no marked differences in adverse events with either treatment approach. Conclusion: The addition of liraglutide and IDeg to patients sub-optimally treated with metformin and liraglutide and requiring treatment intensification was found to be effective and well-tolerated.

AB - Aim: To evaluate the efficacy and safety of adding insulin degludec (IDeg) to treatment in patients with type 2 diabetes receiving liraglutide and metformin and qualifying for treatment intensification because of inadequate glycaemic control. Methods: In this 26-week, double-blind trial, patients who still had inadequate glycaemic control after a 15-week run-in period with initiation and dose escalation of liraglutide to 1.8 mg in combination with metformin (≥1500 mg) were randomized to addition of once-daily IDeg (‘IDeg add-on to liraglutide’ arm; n = 174) or placebo (‘placebo add-on to liraglutide’ arm; n = 172), with dosing of both IDeg and placebo based on titration guidelines. Results: At 26 weeks, the mean change in glycated haemoglobin level was greater in the IDeg add-on to liraglutide arm (−1.04%) than in the placebo add-on to liraglutide arm (−0.16%; p <0.0001). Similarly, the mean fasting plasma glucose reduction was greater, and self-measured plasma glucose values were lower at all eight time points, with IDeg add-on versus placebo add-on (both p <0.0001). At 26 weeks, the IDeg dose was 51 U (0.54 U/kg). During the run-in period with liraglutide, body weight decreased by ∼3 kg in both groups. After 26 weeks, the mean change was +2.0 kg (IDeg add-on to liraglutide) and −1.3 kg (placebo add-on to liraglutide). Confirmed hypoglycaemia rates were low in both groups, although higher with IDeg than with placebo (0.57 vs. 0.12 episodes/patient-years of exposure; p = 0.0002). Nocturnal confirmed hypoglycaemia was infrequent in both groups, with no episodes of severe hypoglycaemia, and no marked differences in adverse events with either treatment approach. Conclusion: The addition of liraglutide and IDeg to patients sub-optimally treated with metformin and liraglutide and requiring treatment intensification was found to be effective and well-tolerated.

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KW - glycaemic control

KW - type 2 diabetes

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