Liraglutide improves peripheral perfusion and markers of angiogenesis and inflammation in people with type 2 diabetes and peripheral artery disease: An 18‐month follow‐up of a randomized clinical trial

Abstract

Abstract Aims In a six‐month randomized clinical trial, improved peripheral perfusion has been shown with liraglutide, associated with favourable vascular effects in people with type 2 diabetes and peripheral artery disease (PAD). We aimed to evaluate the durability of these benefits and to elucidate some mechanisms underlying liraglutide's effect over an 18‐month follow‐up. Methods STARDUST was a randomized clinical trial which compared liraglutide up to 1.8 mg/day with tailored therapeutic prescriptions to manage cardiovascular risk factors in 55 participants with type 2 diabetes and PAD. We report data of people who have reached the 18‐month follow‐up for the primary outcome (transcutaneous oxygen pressure, TcPO 2 ) and also for additional secondary outcomes (markers of inflammation, angiogenesis and kidney function), as well as glycemic and metabolic parameters. TcPO 2 was assessed with transcutaneous oximetry. Circulating levels of angiogenic progenitor cells and serum inflammation markers were evaluated by flow cytometry and enzyme‐linked immunosorbent assay, respectively. Results Compared with the control group, significant differences favouring the liraglutide group were observed at 18 months for TcPO 2 [estimated treated difference (95% CI), 10.9 mmHg (7.6 to 14.1 mmHg), p < 0.001]. At 18 months of follow‐up, participants in the liraglutide group, as compared with those in the control group, had a significant reduction in urine albumin to creatinine ratio (estimated difference, −103.9 mg/g Cr, 95%CI, −170.8 to −37.1, p = 0.003), C‐reactive protein (−0.5 mg/dL, 95%CI, −0.8 to −0.2, p = 0.002), as well as interleukin‐6 (−32.6 pg/mL, 95%CI, −54.6 to −10.5, p = 0.004). Compared with the control group, participants in the liraglutide group showed significantly higher concentrations of circulating progenitor cells and endothelial progenitor cells at both 6 and 18 months, for CD34 + , CD133 + , KDR + , CD34 + /KDR + and CD34 + /CD133 + /KDR + . Liraglutide was also associated with a higher increase in vascular endothelial growth factor A at 18 months (70.1 pg/mL, 95%CI, 44.7 to 95.4, p < 0.001). Conclusions In people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion, with amelioration of markers of angiogenesis and inflammation over an 18‐month follow‐up.