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Effects of liraglutide versus sitagliptin on circulating cardiovascular biomarkers, including circulating progenitor cells, in individuals with type 2 diabetes and obesity: Analyses from the LYDIA trial
Author(s) -
Ahmad Ehtasham,
Waller Helen L.,
Sargeant Jack A.,
Webb M'Balu A.,
Htike Zin Zin,
McCann Gerry P.,
Gulsin Gaurav,
Khunti Kamlesh,
Yates Tom,
Henson Joseph,
Davies Melanie J.,
Webb David R.
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14343
Subject(s) - sitagliptin , liraglutide , medicine , type 2 diabetes , saxagliptin , endocrinology , vascular endothelial growth factor , diabetes mellitus , adiponectin , insulin resistance , vegf receptors
Abstract The mechanisms behind the beneficial cardiovascular effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) compared with dipeptidyl peptidase‐4 inhibitors (DPP4is) remain largely unknown, despite both targeting the incretin pathway to improve glycaemic control. In these prespecified secondary analyses of the LYDIA trial, we examined the impact of the GLP‐1RA liraglutide (1.8 mg once‐daily) and the DPP4i sitagliptin (100 mg once‐daily) on circulating cardiovascular biomarkers associated with atherosclerotic risk, including circulating progenitor cells (CPCs). LYDIA was a 26‐week, randomized, active‐comparator trial in 61 adults with type 2 diabetes and obesity (mean ± SD: age 43.8 ± 6.5 years, body mass index 35.3 ± 6.4 kg/m 2 , HbA1c 7.5% ± 0.83% [58.5 ± 9.1 mmol/mol]). Vascular endothelial growth factor (VEGF) and stromal cell‐derived factor‐1‐alpha (SDF‐1ɑ), both of which are implicated in endothelial function, were higher at 26 weeks with liraglutide therapy compared with sitagliptin (mean between‐group difference [95% CI]: 77.03 [18.29, 135.77] pg/mL, p = .010; and 996.25 [818.85, 1173.64] pg/mL, p < .001, respectively). There were no between‐group differences in CPCs, nitric oxide, C‐reactive protein, interleukin‐6, tumour necrosis factor alpha and advanced glycation end‐products. These analyses suggest a favourable impact of liraglutide on VEGF and SDF‐1ɑ levels compared with sitagliptin. These factors may therefore be implicated in the differential cardiovascular effects observed between these agents in large cardiovascular outcome trials. However, these are secondary analyses from a previous trial and thus hypothesis‐generating. Purposive trials are required to examine these findings further.