ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Thyroid Endocrinology
Risk Factors and Clinical Implications of Thyroxine Replacement Therapy on Major Adverse Cardiovascular Events in Type 2 Diabetes: A Retrospective Cohort Study
Provisionally accepted
- 1Linkou Chang Gung Memorial Hospital, Linkou, Taiwan
- 2Chang Gung University, Taoyuan, Taiwan
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Background: Thyroid hormone replacement therapy is widely used to treat hypothyroidism, but there is limited research on its effects in patients with diabetes mellitus (DM). Some studies indicate that this therapy might improve lipid profiles in DM patients, but even with normalized TSH levels from thyroxine replacement, LDL and total cholesterol levels remain higher than in people with normal thyroid function. Additionally, the effect of this therapy on major adverse cardiovascular events (MACE) in DM patients is still uncertain. Aim: This retrospective study investigated the occurrence of major adverse cardiovascular events (MACE) in participants receiving thyroxine with diabetes and compared the risk factors between the MACE and non-MACE groups. Methods: We used longitudinal claims data from 2008 to 2017 from the Chang Gung Research Database. Individuals with diabetes who used thyroxine were included. The primary outcome was the occurrence of MACE. The secondary outcomes were the differences between the two groups (MACE vs. no MACE). Results: After 1:1 group matching by propensity score between MACE and non-MACE group by sex, age, the interval of using thyroxine, there were 416 patients in each group. Patients with worse renal function (eGFR < 45 ml/min/1.73 m2), hypertension, history of diabetic microvascular complications, end stage renal disease (ESRD), coronary heart disease (CHD), heart failure, cerebrovascular accident (CVA) and diabetic foot infection had a higher risk of experiencing MACE. Free T4 had weak positive correlation with HDL, and TSH had weak positive correlation with LDL and negative correlation with HDL (correlation coefficient, p value: 0.131, 0.022; 0.124, 0.016; -0.157, 0.003, respectively). There’s no optimal cutoff points according to the Receiver operating characteristic (ROC) curve analysis of the best discrimination point between TSH/free T4/LDL and MACE attack. Conclusions: In participants receiving thyroxine with diabetes, patients with worse renal function, hypertension, history of diabetic microvascular complications, ESRD, CHD, heart failure, CVA and diabetic foot infection had a higher risk of experiencing MACE, but peripheral artery disease (PAD) was not a significant risk of MACE.
Keywords: Major adverse cardiovascular events, peripheral artery disease, Risk factors, thyroxine supplement, type 2 diabetes
Received: 10 Oct 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Hsu, Lin, Liu and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yi-Hsuan Lin
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