Endocrinology · Medical Literature
Efficacy of methimazole combined with traditional Chinese medicine in the treatment of Graves' disease: a systematic review and network meta-analysis.
Abstract
Traditional Chinese Medicine (TCM) Combined with Methimazole (MMI) versus MMI Alone for Thyroid Function and Autoantibodies in Graves' Disease(GD). A systematic literature search was performed in PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, VIP, CBM, and Wanfang databases up to June 2025 for RCTs comparing TCM plus MMI versus MMI alone. Study risk of bias was evaluated using the Cochrane tool. We assessed transitivity to ensure intervention comparability, verified consistency via node-splitting analysis, and planned sensitivity analysis according to risk-of-bias classification. A network meta-analysis was conducted in Stata 15.1 using a random-effects model. Results are reported as mean differences (MD) or standardized mean differences (SMD) with 95% confidence intervals (CI), and treatment efficacy was ranked using SUCRA values. A network meta-analysis of 15 RCTs involving 1,317 GD patients and 14 TCM plus MMI regimens showed potential advantages over MMI alone in improving thyroid function indices and reducing selected autoantibodies, particularly TRAb and TPOAb. Adverse events were summarized descriptively because AE reporting was incomplete and heterogeneous across the included RCTs. Regarding SUCRA rankings, the Modified Huagan Decoction (MHD) + MMI ranked first for reducing FT3 (SUCRA = 93.4%), the Modified Xiaoyao Powder (MXYP) + MMI ranked first for reducing FT4 (SUCRA = 97.3%), and the Xiaoyao Powder (XYP) + MMI ranked first for regulating TSH (SUCRA = 96.3%). For decreasing TRAb, the MHD + MMI regimen ranked first (SUCRA = 88.2%), while for lowering TPOAb, the Huotan Jiangni Formula (HJF) + MMI showed the highest SUCRA ranking (SUCRA = 100%). TCM combined with MMI may have beneficial effects on thyroid function and selected autoantibody levels, particularly TRAb and TPOAb, in GD patients versus MMI alone. Among the evaluated regimens, MHD + MMI, MXYP + MMI, XYP + MMI, and HJF + MMI showed high SUCRA rankings for specific outcomes, including FT3, FT4, TSH, TRAb, and TPOAb. These findings suggest that TCM plus MMI may be a promising short-term adjunctive strategy for initial GD treatment, although safety evidence remains limited by incomplete and inconsistent AE reporting. https://www.crd.york.ac.uk/prospero/, identifier CRD420251151307.
Clinical relevance
Graves' disease affects a significant proportion of patients with hyperthyroidism, and methimazole (MMI) monotherapy is associated with high relapse rates and adverse effects, leaving a clinical gap for adjunctive strategies. This network meta-analysis addresses whether Traditional Chinese Medicine (TCM) formulations, when combined with MMI, can meaningfully improve thyroid function indices and autoantibody profiles compared to MMI alone. As integrative medicine approaches gain traction globally and a substantial portion of GD patients in East Asia already use TCM adjuncts, this evidence synthesis is timely and directly relevant to endocrinologists managing newly diagnosed or relapsing GD.
Key findings
1. The network meta-analysis included 15 RCTs with 1,317 GD patients evaluating 14 distinct TCM plus MMI combination regimens versus MMI alone, providing a broad comparative framework via random-effects modeling with results expressed as MD or SMD with 95% CIs. 2. Modified Huagan Decoction (MHD) + MMI ranked highest for reducing free triiodothyronine (FT3), achieving a SUCRA value of 93.4%, suggesting superior efficacy among all evaluated regimens for this outcome. 3. Modified Xiaoyao Powder (MXYP) + MMI ranked first for reducing free thyroxine (FT4) with a SUCRA of 97.3%, indicating a high probability of being the most effective regimen for normalizing FT4 levels. 4. Xiaoyao Powder (XYP) + MMI ranked first for TSH regulation with a SUCRA of 96.3%, implying a strong comparative advantage in restoring pituitary-thyroid axis feedback suppression. 5. For TRAb reduction — a key autoantibody driving GD pathophysiology — MHD + MMI ranked first (SUCRA = 88.2%), while Huotan Jiangni Formula (HJF) + MMI achieved the highest SUCRA of 100% for lowering TPOAb, the top ranking across all outcomes reported. 6. Adverse event data could not be pooled quantitatively due to incomplete and heterogeneous AE reporting across the included RCTs, precluding formal safety comparisons and representing a critical evidence gap.
Practice implications
Endocrinologists treating newly diagnosed GD patients — particularly those in integrative medicine settings or with patient preference for adjunctive therapies — may consider that specific TCM formulations (notably MHD, MXYP, XYP, and HJF) combined with standard MMI dosing appear to offer incremental benefits in normalizing FT3, FT4, TSH, TRAb, and TPOAb compared to MMI alone, though effect sizes should be interpreted cautiously given the network meta-analytic design and underlying RCT heterogeneity. Patient selection should currently be limited to those receiving MMI as part of initial short-term GD management, as the evidence is characterized as a 'promising short-term adjunctive strategy' with no robust long-term relapse or remission data available. Clinicians must exercise caution regarding safety: the inability to perform quantitative AE analysis due to incomplete reporting means that hepatotoxicity, agranulocytosis interactions, and herb-drug interactions remain uncharacterized, necessitating vigilant monitoring and pharmacovigilance until higher-quality safety data are available.