Long‐term efficacy and safety of combined insulin and glucagon‐like peptide‐1 therapy: Evidence from the LEADER trial

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.