Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease

Importance Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. Objective To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcP o 2 ) in individuals with type 2 diabetes and PAD. Design, Setting, and Participants This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania “Luigi Vanvitelli,” Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcP o 2 between 30 and 49 mm Hg were included. Interventions Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Main Outcomes and Measures Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcP o 2 from baseline in each group. Results Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A 1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcP o 2 of 40.3 (5.7) mm Hg. Transcutaneous P o 2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcP o 2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (−0.4 mg/dL; 95% CI, −0.7 to −0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (−119.4 mg/g; 95% CI, −195.0 to −43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). Conclusions and Relevance In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcP o 2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. Trial Registration ClinicalTrials.gov Identifier: NCT04881110