Ketan Dhatariya1,2, Stephen C Bain3, John B Buse4, Richard Simpson5, Lise Tarnow6, Margit Staum Kaltoft7, Michael Stellfeld7, Karen Tornøe7, Richard E Pratley8. 1. Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, U.K. ketan.dhatariya@nnuh.nhs.uk. 2. Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, U.K. 3. Institute of Life Science, Swansea University Medical School, Swansea, U.K. 4. University of North Carolina School of Medicine, Chapel Hill, NC. 5. Eastern Health Clinical School, Monash University, Box Hill, Victoria, Australia. 6. Nordsjællands Hospital, Hillerød, Denmark. 7. Novo Nordisk A/S, Søborg, Denmark. 8. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL.
Abstract
OBJECTIVE:Diabetes-related foot ulcers (DFUs) and their sequelae result in large patient and societal burdens. Long-term data determining the efficacy of individual glucose-lowering agents on DFUs are lacking. Using existing data from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, we conducted post hoc analyses assessing the impact of liraglutide versus placebo in people with type 2 diabetes and at high risk of cardiovascular (CV) events on the incidence of DFUs and their sequelae. RESEARCH DESIGN AND METHODS: The LEADER trial (NCT01179048) was a randomized, double-blind, multicenter, CV outcomes trial assessing liraglutide (1.8 mg/day) versus placebo, in addition to standard of care, for up to 5 years. Information on DFUs was collected systematically during the trial, and DFU complications were assessed post hoc through reviewing case narratives. RESULTS: During a median of 3.8 years' follow-up, similar proportions of patients reported at least one episode of DFU in the liraglutide and placebo groups (3.8% [176/4,668] versus 4.1% [191/4,672], respectively; hazard ratio [HR] 0.92 [95% CI 0.75, 1.13; P = 0.41]). Analysis of DFU-related complications demonstrated a significant reduction in amputations with liraglutide versus placebo (HR 0.65 [95% CI 0.45, 0.95; P = 0.03]). However, no differences were found for foot infections, involvement of underlying structures, or peripheral revascularization in the main analysis. CONCLUSIONS: Treatment with liraglutide in patients with type 2 diabetes and at high risk of CV events in the LEADER trial did not increase the risk of DFU events and was associated with a significantly lower risk of DFU-related amputations compared with placebo. This association, possibly due to chance, needs further investigation.
RCT Entities:
OBJECTIVE:Diabetes-related foot ulcers (DFUs) and their sequelae result in large patient and societal burdens. Long-term data determining the efficacy of individual glucose-lowering agents on DFUs are lacking. Using existing data from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, we conducted post hoc analyses assessing the impact of liraglutide versus placebo in people with type 2 diabetes and at high risk of cardiovascular (CV) events on the incidence of DFUs and their sequelae. RESEARCH DESIGN AND METHODS: The LEADER trial (NCT01179048) was a randomized, double-blind, multicenter, CV outcomes trial assessing liraglutide (1.8 mg/day) versus placebo, in addition to standard of care, for up to 5 years. Information on DFUs was collected systematically during the trial, and DFU complications were assessed post hoc through reviewing case narratives. RESULTS: During a median of 3.8 years' follow-up, similar proportions of patients reported at least one episode of DFU in the liraglutide and placebo groups (3.8% [176/4,668] versus 4.1% [191/4,672], respectively; hazard ratio [HR] 0.92 [95% CI 0.75, 1.13; P = 0.41]). Analysis of DFU-related complications demonstrated a significant reduction in amputations with liraglutide versus placebo (HR 0.65 [95% CI 0.45, 0.95; P = 0.03]). However, no differences were found for foot infections, involvement of underlying structures, or peripheral revascularization in the main analysis. CONCLUSIONS: Treatment with liraglutide in patients with type 2 diabetes and at high risk of CV events in the LEADER trial did not increase the risk of DFU events and was associated with a significantly lower risk of DFU-related amputations compared with placebo. This association, possibly due to chance, needs further investigation.
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