Related Experiment Video
Updated: Feb 3, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Liraglutide and Glycaemic Outcomes in the LEADER Trial
Bernard Zinman1, Michael A Nauck2, Heidrun Bosch-Traberg3
1Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada. zinman@lunenfeld.ca.
Insights
Liraglutide significantly improved glycemic control in type 2 diabetes patients at high cardiovascular risk, reducing HbA1c and delaying glycemic deterioration compared to placebo. However, progressive loss of glycemic control was observed in both groups over time.
Area of Science:
- Cardiology
- Endocrinology
- Metabolic Diseases
Background:
- The LEADER trial assessed cardiovascular outcomes in type 2 diabetes patients at high CV risk, comparing liraglutide to placebo.
- This post hoc analysis specifically investigated glycemic outcomes in these patient groups.
Purpose of the Study:
- To evaluate the efficacy of liraglutide in improving glycemic control in high-risk type 2 diabetes patients.
- To compare the incidence of glycemic deterioration between liraglutide and placebo treatment arms.
Main Methods:
- HbA1c levels were measured serially throughout the study.
- Cox regression analysis was used to assess time to glycemic deterioration, defined by HbA1c changes or medication intensification.
- Individual components of glycemic deterioration were also analyzed.
Main Results:
- Liraglutide demonstrated a greater reduction in HbA1c compared to placebo, with an estimated treatment difference of -0.40% at 36 months.
- Fewer patients on liraglutide experienced glycemic deterioration (68.6%) versus placebo (85.4%).
- The risk of glycemic deterioration was significantly lower with liraglutide (HR 0.50; P < 0.001).
Conclusions:
- Liraglutide treatment led to superior HbA1c reductions and less glycemic deterioration in high-risk type 2 diabetes patients compared to placebo.
- Despite improvements, progressive loss of glycemic control was noted in both treatment groups.
- Liraglutide was associated with a lower risk of hypoglycaemia and less need for medication intensification.
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 (HbA1c) 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 HbA1c 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. HbA1c 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 HbA1c, 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.
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