Once‐weekly glucagon‐like peptide receptor agonist polyethylene glycol loxenatide protects against major adverse cardiovascular events in patients with type 2 diabetes: a multicenter ambispective cohort study (FLYING trial)

Abstract This study aimed to determine the effects of polyethylene glycol loxenatide (PEG‐Loxe), a glucagon‐like peptide‐1 receptor agonist, on a three‐point major adverse cardiovascular event (3P‐MACE) in patients with type 2 diabetes mellitus (T2DM). The study was conducted in six tertiary hospitals in three cities in China. Large language models were used to retrospectively screen and include 12,341 patients with T2DM who had either cardiovascular disease or cardiovascular risk factors. The patients were divided into the PEG‐Loxe cohort (treated with PEG‐Loxe, n = 1282) and the control cohort (treated with incretin glucose‐lowering agents, n = 11,059). After a median follow‐up of 4.0 years, 3P‐MACE occurred in 51 (4.0%) and 1263 (11.4%) patients in PEG‐Loxe and control cohorts, respectively (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49–0.94; p = 0.019). In the PEG‐Loxe versus control cohorts, 21 (1.6%) versus 476 (4.3%) patients experienced nonfatal stroke (HR 0.63; p = 0.041), whereas 22 (1.7%) versus 545 (4.9%) experienced nonfatal myocardial infarction (HR 0.66; p = 0.058), and the incidence of cardiovascular death was 8 (0.6%) versus 240 (2.2%), respectively (HR 0.56; p = 0.118). We found a significantly lower incidence of first nonfatal myocardial infarction, nonfatal stroke, or cardiovascular deaths in the PEG‐Loxe cohort than the control cohort.