Liraglutide and Glycaemic Outcomes in the LEADER Trial.

INTRODUCTION

The LEADER trial was a cardiovascular (CV) outcomes trial in patients with type 2 diabetes at high CV risk that compared liraglutide (n = 4668) with placebo (n = 4672) using a primary composite endpoint of 3-point major adverse CV events. The objective of this post hoc analysis was to investigate glycaemic outcomes across both treatment groups.

METHODS

Glycated haemoglobin (HbA) was measured at randomisation, month 3, month 6 and every 6 months thereafter. Cox regression was used to analyse time to a composite endpoint of glycaemic deterioration, defined as a specified change in HbA or a substantial intensification of insulin or oral antihyperglycaemic drug (OAD). The individual components of the composite were also analysed.

RESULTS

Baseline characteristics, including insulin and OAD use, were balanced between treatment groups. HbA decreased from baseline in both groups, but the reduction was greater with liraglutide [estimated treatment difference at month 36: - 0.40%; 95% confidence interval (CI) - 0.45, - 0.34] despite the addition of more OADs and higher insulin use in the placebo group. Fewer of the patients treated with liraglutide (n = 3202, 68.6%) experienced glycaemic deterioration compared with those administered the placebo (n = 3988, 85.4%; average hazard ratio: 0.50; 95% CI 0.48, 0.53; p < 0.001). Analysis of the individual components showed similar results (both p  < 0.001).

CONCLUSIONS

Type 2 diabetes patients at high risk of CV events who were treated with liraglutide achieved greater reductions in HbA, had a lower risk of hypoglycaemia and presented less glycaemic deterioration than similar patients who received the placebo. Nonetheless, progressive loss of glycaemic control occurred in both groups.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT01179048.

FUNDING

Novo Nordisk. Plain language summary available for this article.