Table 1 Current status of research into thyroid-related therapeutic agents for MASLD
Compound | Mechanism | Objects | Main effects | Adverse reaction | Research status | References |
|---|---|---|---|---|---|---|
L-T4 | Direct regulation of hepatic cholesterol and triglyceride metabolism | NASH mouse models | Liver TAG↓ Liver Hyp↓ Liver Lipid Types↓ Fatty acid oxidation↑ | Adverse effects of high doses of TH on the heart and bones | Further clinical trials are still needed to validate the benefits of L-T4 supplementation in MASLD | [70] |
|  |  | SCH patients (363 persons) | Prevalence of MASLD↓ Serum AST↓ Serum TC↓ Weight and BMI↓ |  |  | [71] |
|  |  | Patients with T2DM combined with MASLD (47 persons) | IHLC↓ BMI↓ Visceral adipose tissue volume↓ Subcutaneous adipose tissue volume↓ |  |  | [69] |
3,5-diiodo-L-thyronine (T2) | To increase hepatic mitochondrial oxygen consumption and fatty acid metabolism | High-fat diet rat models | Weight↓ Fatty acid oxidation↑ SerumTAG↓,TC↓,ALT↓ Carnitine palmitoyltransferase activity↑ Serum TH and TSH are not affected | No adverse effects were observed at the cardiac level for the time being | Lack of larger trials; now focusing on the therapeutic potential of functional T2 analogs | |
|  |  | Subjects with normal thyroid function (2 persons) | RMR↑ Weight↓ Serum FT3,FT4,TSH are not affected |  |  | [75] |
TRC150094 | Functional T2 analog | High-fat diet rat models | Visceral adipose tissue volume↓ Fatty acid oxidation↑ | Adverse effects in subjects were not related to treatment | Phase III clinical trial underway | [76] |
|  |  | Dyslipidemic subjects (225 persons) | FPG↓ Fasting insulin↓ Mean arterial pressure↓ Non-HDL cholesterol↓ |  |  | [77] |
Sobetirome (GC-1) | Hepatic selective THR agonist | Cholesterol-Fed Rats and Crab-Eating Monkeys | Weight↓ Serum TC,TAG↓ Lp-a ↓ MVO2 ↑ | Some degree of TSH suppression was observed as well as reduced hepatic insulin sensitivity | Subsequent clinical trials were not performed due to decreased hepatic insulin sensitivity and increased endogenous glucose production | |
eprotirome (KB2115) | Liver-specific THR agonist | High-fat diet rat models | Liver TAG↓ Serum LDL↓ | Decreased glucose uptake in skeletal muscle; Potential for liver injury; cartilage damage in dogs | Phase III clinical trial terminated early due to cartilage damage identified in dog toxicology study | [80] |
|  |  | Patients with high cholesterol or overweight (24 persons) | Serum LDL↓ Serum TC↓ Serum apoB↓ Bile acid synthesis↑ |  |  | [59] |
|  |  | Familial high cholesterol patients ( 236 persons) | SerumLDL↓ Liver TAG↓ Bile acid synthesis↑ Transaminases, bilirubin↑ |  |  | [81] |
VK2809 (MB07811) | Prodrug for hepatic THRβ-selective active drug (MB07344) | Rabbits, dogs, monkeys | Serum TC↓ | No significant cardiovascular effects observed | Another Phase II clinical trial is underway | [83] |
|  |  | Mouse models of glycogen storage disease | Hepatic steatosis↓ Mouse liver mass↓ Intrahepatic TAG↓ Hepatic fatty acid oxidation↑ |  |  | [85] |
|  |  | High cholesterol and MASLD patients (45 persons) | Liver fat content↓ Hepatic steatosis↓ Hepatic fatty acid oxidation↑ |  |  | [86] |
TG68 | Novel selective agonist of THRβ | High-fat diet mouse model | Liver weight↓ Hepatic steatosis↓ Serum TAG↓ | No adverse reactions have been detected for the time being | More preclinical studies are lacking, but current evidence shows its therapeutic potential | [87] |
|  |  | DEN induction with high-fat-fed rat models | Liver weight↓ Hepatic steatosis↓ Serum TAG↓ Regression of pre-tumor lesions |  |  | [88] |
Resmetirom (MGL-3196) | Liver-directed, THRβ-selective agonist | NASH patients (348 persons) | Liver fat content↓ Liver TC↓ Indicators of Liver Injury and Liver Fibrosis↓ HRQL Improvement | Generally well tolerated | Further phase III clinical trials are underway | |
|  |  | NASH patients (1143 persons) | The majority of TEAEs were of mild to moderate severity Atherogenic lipid levels↓ |  |  | [91] |
|  |  | NASH patients (966 persons) | NASH resolution without worsening fibrosis Fibrosis improvement Low-density lipoprotein cholesterol↓ |  |  | [92] |
|  |  | Late-stage NASH mouse model | Liver fat content↓ Liver TC↓ Serum TAG↓ |  |  | [93] |