(A-178) The association between fibrate use and the risk of diabetic peripheral vascular disease in patients with type 2 diabetes mellitus: A nested case-control study

Background: Type 2 diabetes mellitus (T2DM) significantly increases the risk of diabetic peripheral vascular disease (PVD). Determining whether fibrate therapy reduces the risk of developing diabetic PVD may help target management strategies in this population.

Objectives: To investigate the association between fibrate use and the risk of developing diabetic PVD in patients with T2DM.

Methods: This study used an active comparator new-user design with a matched nested case-control study (1:4 propensity score matching by age and gender). The initial cohort consisted of patients with T2DM who were newly filled fibrates or statins (control group) between January 1, 2012, and December 31, 2022 and received at least two prescriptions in the 6-month baseline period were identified from the Yinzhou Regional Health Information Platform (YRHIP) in Ningbo, China. A nested case-control study cohort was subsequently derived from this initial cohort. After matching the inverse probability of treatment weighted (IPTW) Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between fibrate use and diabetic PVD incidence compared with statins. Subgroups with heterogeneous treatment effects were identified using the causal forest method, and predefined groupings were determined in conjunction with clinical expertise. Finally, subgroup analyses were performed based on baseline age, gender, BMI, history of dyslipidemia, history of peripheral vascular disease, fasting blood glucose levels, triglyceride, low-density lipoprotein levels, and duration of T2DM. Sensitivity analyses included competing risk analysis and extending the latency period.

Results: A total of 2,370 participants were included, comprising 193 new fibrate users and 2,177 new statin users. During the follow-up period, 474 new cases of diabetic PVD were identified, with incidence rates of 646.36 per 10,000 person-years in the fibrate group and 565.35 per 10,000 person-years in the statin group. Compared to statin use, IPTW Cox models indicated that fibrate use was associated with a reduced risk of diabetic PVD [HR:0.54, 95%CI: 0.32~0.93]. Subgroup analysis suggests that patients with a history of dyslipidemia benefit more from fibrate therapy. Sensitivity analyses were consistent with these primary findings.

Conclusions: Among patients with T2DM in Yinzhou, Ningbo, fibrate use may be associated with a reduced risk of diabetic PVD compared to statin use. These findings provide evidence for the potential use of lipid-lowering medications in the prevention and management of diabetic PVD in T2DM patients.