Long-term efficacy and safety of combined insulin and glucagon-like peptide-1 therapy

Evidence from the LEADER trial

the LEADER Publication Committee on behalf of the LEADER Trial Investigators

Research output: Contribution to journalArticle

Abstract

Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long-term data are lacking. The aim was to assess the long-term efficacy of the GLP-1RA liraglutide in subgroups by insulin use in the LEADER trial. Materials and Methods: LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal-only insulin, other insulin or no insulin). Insulin was a non-random treatment allocation as part of standard of care therapy. Results: At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal-only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no-insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P <.001), and severe hypoglycaemia rate in the basal-only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal-only and no-insulin subgroups. Conclusions: In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.

Original languageEnglish (US)
JournalDiabetes, Obesity and Metabolism
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Glucagon-Like Peptide 1
Insulin
Safety
Therapeutics
Hypoglycemia
Type 2 Diabetes Mellitus
Placebos
Standard of Care
Insulins
Weights and Measures
Risk Reduction Behavior

Keywords

  • glucagon-like peptide-1 analogue
  • insulin analogues
  • insulin therapy
  • liraglutide
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Long-term efficacy and safety of combined insulin and glucagon-like peptide-1 therapy : Evidence from the LEADER trial. / the LEADER Publication Committee on behalf of the LEADER Trial Investigators.

In: Diabetes, Obesity and Metabolism, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long-term data are lacking. The aim was to assess the long-term efficacy of the GLP-1RA liraglutide in subgroups by insulin use in the LEADER trial. Materials and Methods: LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal-only insulin, other insulin or no insulin). Insulin was a non-random treatment allocation as part of standard of care therapy. Results: At baseline, 5171 (55{\%}) patients were not receiving insulin, 3159 (34{\%}) were receiving basal-only insulin and 1010 (11{\%}) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no-insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P <.001), and severe hypoglycaemia rate in the basal-only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal-only and no-insulin subgroups. Conclusions: In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.",
keywords = "glucagon-like peptide-1 analogue, insulin analogues, insulin therapy, liraglutide, type 2 diabetes",
author = "{the LEADER Publication Committee on behalf of the LEADER Trial Investigators} and Tack, {Cees J.} and Stephan Jacob and Desouza, {Cyrus V} and Bain, {Stephen C.} and Buse, {John B.} and Nauck, {Michael A.} and Petrie, {John R.} and Poulter, {Neil R.} and Pratley, {Richard E.} and Stegmann, {Helen Vanya B.K.} and Heidrun Bosch-Traberg and Elena Startseva and Bernard Zinman",
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T2 - Evidence from the LEADER trial

AU - the LEADER Publication Committee on behalf of the LEADER Trial Investigators

AU - Tack, Cees J.

AU - Jacob, Stephan

AU - Desouza, Cyrus V

AU - Bain, Stephen C.

AU - Buse, John B.

AU - Nauck, Michael A.

AU - Petrie, John R.

AU - Poulter, Neil R.

AU - Pratley, Richard E.

AU - Stegmann, Helen Vanya B.K.

AU - Bosch-Traberg, Heidrun

AU - Startseva, Elena

AU - Zinman, Bernard

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Y1 - 2019/1/1

N2 - Aim: Glucagon-like peptide-1 receptor agonist (GLP-1RA) and insulin combination therapy is an effective treatment option for type 2 diabetes, but long-term data are lacking. The aim was to assess the long-term efficacy of the GLP-1RA liraglutide in subgroups by insulin use in the LEADER trial. Materials and Methods: LEADER assessed cardiovascular (CV) safety and efficacy of liraglutide (1.8 mg) versus placebo (plus standard of care therapy) in 9340 patients with type 2 diabetes and high risk of CV disease, for up to 5 years. We analyzed CV events, metabolic parameters and hypoglycaemia post hoc in three subgroups by baseline insulin use (basal-only insulin, other insulin or no insulin). Insulin was a non-random treatment allocation as part of standard of care therapy. Results: At baseline, 5171 (55%) patients were not receiving insulin, 3159 (34%) were receiving basal-only insulin and 1010 (11%) other insulins. Insulin users had a longer diabetes duration and slightly worse glycaemic control (HbA1c) than the no-insulin subgroup. Liraglutide reduced HbA1c and weight versus placebo in all three subgroups (P <.001), and severe hypoglycaemia rate in the basal-only insulin subgroup. The need for insulin was less with liraglutide. CV risk reduction with liraglutide was similar to the main trial results in the basal-only and no-insulin subgroups. Conclusions: In patients on insulin, liraglutide improved glycaemic control, weight and need for insulin versus placebo, for at least 36 months with no increased risk of severe hypoglycaemia, while maintaining CV safety/efficacy, supporting the combination of liraglutide and insulin for management of type 2 diabetes.

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KW - insulin analogues

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KW - liraglutide

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