Ursodeoxycholic Acid
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Ursodeoxycholic Acid
- Ursodeoxycholic Acid: From Gallstone Disease and Primary Biliary Cholangitis to Homozygous Familial Hypercholesterolemia
Ursodeoxycholic Acid: From Gallstone Disease and Primary Biliary Cholangitis to Homozygous Familial Hypercholesterolemia
One-Sentence Summary
Ursodeoxycholic acid (UDCA) was originally used to treat gallstone disease (cholelithiasis, cholecystolithiasis, choledocholithiasis) and primary biliary cholangitis. The TxGNN model predicts it may be effective for homozygous familial hypercholesterolemia, but no clinical trials and no publications currently support this prediction, so it is a computational prediction only. The best-supported alternative among the top 10 predictions is diabetic nephropathy, which has 7 publications (mostly preclinical) and one possible early human study.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Cholelithiasis, cholecystolithiasis, choledocholithiasis, primary biliary cholangitis, Reynolds syndrome (from the knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Homozygous familial hypercholesterolemia |
| TxGNN Prediction Score | 99.86% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, UDCA is a bile acid used in cholestatic and gallstone disorders. It reduces intestinal cholesterol absorption and hepatic cholesterol secretion, so a link to lipid handling is plausible.
However, homozygous familial hypercholesterolemia is driven by LDL receptor dysfunction. Bile acid modulation is unlikely to replace LDL-lowering therapy, so this link is speculative and not evidence-based. The high score (99.86%) reflects a network-based computational association only.
Other predicted indications (ranks 2-10)
| Rank | Predicted Indication | Score | Evidence Level | Comment |
|---|---|---|---|---|
| 2 | Brain small vessel disease 1 (COL4A1) | 98.31% | L5 | Hypothesis only: chemical-chaperone / ER-stress relief; no data |
| 3 | Familial hematuria-retinal arteriolar tortuosity-contractures syndrome (COL4A1-related) | 98.30% | L5 | Same speculative rationale; no data |
| 4 | Pseudo-von Willebrand disease | 97.21% | L5 | No clear mechanistic link |
| 5 | Primary release disorder of platelets | 97.07% | L5 | No plausible link |
| 6 | Primary hyperoxaluria | 96.89% | L5 | No known effect on oxalate synthesis |
| 7 | Diabetic nephropathy | 96.69% | L3 | Coherent preclinical rationale; one possible human study |
| 8 | Glanzmann thrombasthenia | 96.10% | L5 | No credible link |
| 9 | Familial combined hyperlipidaemia (obsolete term) | 96.05% | L5 | Tenuous rationale |
| 10 | Hypolipoproteinaemia | 96.04% | L5 | Only literature item is an unrelated case report |
Diabetic nephropathy is the only one of these with a coherent mechanistic story. Preclinical studies suggest UDCA/TUDCA relieves ER stress and oxidative stress in kidney cells, prevents podocyte apoptosis, reduces SGLT2 expression, and limits ER-stress-driven inflammasome activation.
Clinical Trial Evidence
Currently no related clinical trials registered for the top-ranked prediction (homozygous familial hypercholesterolemia). No registered trials were found for the other nine predictions either.
Literature Evidence
No literature is available for homozygous familial hypercholesterolemia. The table below covers the best-supported alternative, diabetic nephropathy (rank 7).
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 42857346 | 2026 | Human clinical study (proof-of-concept; design to be verified) | Front Endocrinol | Examines UDCA's effect on albuminuria in type 1 diabetes with diabetic kidney disease; results not verifiable from the available abstract |
| 27193377 | 2016 | Preclinical (animal/in vitro) | Biol Pharm Bull | UDCA, as an ER-stress inhibitor, reduced hyperglycaemia-related oxidative stress and improved nephropathy in db/db mice |
| 26999661 | 2016 | Preclinical (animal) | Lab Invest | UDCA and 4-PBA prevented ER-stress-induced podocyte apoptosis in diabetic nephropathy in db/db mice |
| 22429686 | 2012 | Preclinical (animal) | Diabetes Res Clin Pract | UDCA decreased renal SGLT2 expression and oxidative stress in diabetic rats |
| 18648192 | 2008 | Preclinical (in vitro) | Am J Nephrol | Taurine-conjugated UDCA reduced ER stress and apoptosis induced by advanced glycation end products in mouse podocytes |
| 23977286 | 2013 | Preclinical (mechanistic) | PLoS One | ER stress is involved in albuminuria-induced inflammasome activation in renal tubular cells (supports the mechanism) |
| 39384774 | 2024 | Observational metabolomic | Nutr Diabetes | Bile acid metabolism is altered step-wise in diabetic kidney disease (background association) |
The only literature item for hypolipoproteinaemia (PMID 26176881) is a case report on fibrinogen storage disease. It does not test UDCA and provides no evidence of benefit.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN05742P | URSOFALK CAPSULE 250 mg | Capsule | Not stated in the available data |
| SIN16918P | URSOSAN FORTE FILM-COATED TABLETS 500MG | Film-coated tablet | Not stated in the available data |
| SIN15883P | GRINTEROL HARD CAPSULE 250MG | Capsule | Not stated in the available data |
| SIN16926P | URSOSAN HARD CAPSULES 250 MG | Capsule | Not stated in the available data |
| SIN14545P | URSOFALK FILM-COATED TABLETS 500MG | Film-coated tablet | Not stated in the available data |
All five registrations are single-ingredient products, valid, and oral.
Safety Considerations
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for safety information.
Drug Interactions: The interaction screen returned 100 interacting drugs. Most have an unclassified severity. The entries reviewed include:
- Minor: cyclosporine, aluminium hydroxide, magaldrate (antacids containing aluminium may reduce UDCA absorption)
- Severity not classified: pravastatin, ramipril, lorazepam, tramadol, fluconazole, erythromycin, sildenafil, pantoprazole, citalopram, moxifloxacin, nelfinavir, indinavir, glimepiride, oseltamivir, cyanocobalamin, calcitriol, folic acid
The remaining entries were not reviewed here. A full interaction review is needed before any new use.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction (homozygous familial hypercholesterolemia) rests on a score alone, with no trials or publications, and a speculative mechanism. Nine of the ten predictions are at L5. Only diabetic nephropathy reaches L3, and that rests mainly on preclinical work plus one unverified human study. That is a research question rather than a basis for a go decision.
To proceed, the following is needed:
- Confirm the design, population, and results of the 2026 proof-of-concept study (PMID 42857346) in type 1 diabetes with kidney disease. If it holds up, consider re-evaluating diabetic nephropathy as the lead indication.
- Mechanism of action data for UDCA, which was not available for this report.
- Package insert warnings and contraindications from the Singapore regulator, which are required before safety screening.
- A search for registered trials in diabetic kidney disease.
- If the lipid indication is pursued, a rationale for how bile acid modulation could add to LDL-lowering therapy in a receptor-deficient disease.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.