The Effects of Anti-thyroid Drugs on Lipoproteins and Insulin Resistance in Graves’ Disease: A Randomized Clinical Trial

Abstract

Objective: Graves’ disease (GD) is characterized by thyroid overactivity. Anti-thyroid drugs (ATDs), such as propylthiouracil (PTU) and methimazole (MMI), are commonly used for GD treatment, and studies have suggested a link between these drugs and elevated lipoprotein levels. However, data on their effects on lipoproteins, insulin resistance, or low-density lipoprotein receptor (LDL-R) levels are lacking, both in Indonesia and in other countries. This study investigated changes in lipoproteins, LDL-R, and insulin resistance markers with ATD treatment. Methods: This study is a secondary analysis of a randomized clinical trial entitled “The Differential Effects of Propylthiouracil and Methimazole as Graves’ Disease Treatment on Vascular Atherosclerosis Markers” conducted in Jakarta, Indonesia. Thirty-seven newly diagnosed GD patients received MMI or PTU for 3 months. Results: After 3 months of ATD treatment, LDL-R levels significantly decreased compared to baseline (197 vs. 144 ng/mL, p<0.001), while most lipoproteins, including TC, LDL-C, HDL-C, non-HDL-C, the cholesterol ratio, and the LDL-C/HDL-C ratio, increased. Unexpectedly, neither the PTU nor MMI groups showed an increased dyslipidemia prevalence. Although body mass index increased significantly and fasting plasma glucose decreased slightly, no significant post-treatment change in insulin resistance was observed. The study received ethical approval from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (ref KET-784/ UN.2.F1/ETIK/PPM.00.02/2019) and was registered on clinicaltrials.gov (NCT05118542). Conclusion: ATD treatment for GD led to a significant increase in total cholesterol, LDL-cholesterol, and high-density lipoprotein-cholesterol levels, along with a reduction in LDL-R levels. Both PTU and MMI showed similar effects. These findings provide valuable insights into the effects of ATDs on lipoproteins and insulin resistance in GD patients.