Efficacy and Safety of Adjunctive Bile Acid Sequestrant Therapy for Thyrotoxicosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background:

Bile acid sequestrants have been reported to reduce serum thyroid hormone levels by binding T4 and T3 excreted into the intestinal lumen, preventing their reabsorption into the systemic circulation and interrupting the enterohepatic circulation of these hormones. This meta-analysis evaluates whether adjunctive bile acid sequestrants accelerate reductions in serum iodothyronine when added to standard hyperthyroidism therapy.

Methods:

A systematic review and meta-analysis were conducted and registered in PROSPERO (CRD42025643217). MEDLINE, Embase, Web of Science, and Cochrane databases were searched from March 1971 to September 2025 for randomized controlled trials (RCTs) assessing adult non-critically ill patients with hyperthyroidism treated with standard therapy (thionamides and beta-blocker) plus adjunctive bile acid sequestrants (cholestyramine or colestipol) versus standard therapy alone. Primary outcomes included a reduction in serum-free T4 and total T3. The secondary outcome was adverse effect frequency.

Results:

Initial search yielded 705 results. After removal of duplicates and title/abstract screening, 17 full-text articles were reviewed, and five RCTs met the inclusion criteria, totaling 173 adult patients: 93 (53.75%) received adjunctive therapy, and 80 (46.25%) were controls. Causes for thyrotoxicosis included Graves’ disease, toxic adenoma, and multinodular goiter. Doses ranged from cholestyramine 1 g twice a day to 4 g four times a day, and colestipol 20 g daily. At 2 weeks of treatment, bile acid sequestrants showed a non-significant reduction in serum total T3 (mean difference [MD] −0.44 nmol/L, 95% confidence interval [CI]: −1.2 to +0.32) and free T4 level (MD –0.55 ng/dL, CI: −1.15 to +0.04). At 4 weeks, there was a statistically significant reduction in total T3 (MD –1.59 nmol/L, CI: −2.90 to −0.27) and free T4 level (MD −1 ng/dL, CI: −1.74 to −0.25).

Conclusions:

Adjunctive bile acid sequestrants with standard hyperthyroidism therapy appear to enhance reductions in serum total T3 and free T4 at the mark of four weeks and were well tolerated. However, due to considerable heterogeneity and low quality of evidence, our results should be interpreted with caution. Larger, high-quality RCTs are needed to strengthen the evidence regarding the efficacy of adjunctive bile acid sequestrant therapy.