Sacubitril
| Evidence Level: L5 | Predicted Indications: 5 |
Table of Contents
- Sacubitril
- Pharmacist Assessment Report
- Sacubitril: Brain small vessel disease 1 with or without ocular anomalies
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Safety Considerations
- Conclusion and Next Steps
- Review Log
- Disclaimer
Sacubitril: Brain small vessel disease 1 with or without ocular anomalies
One-Sentence Summary
Sacubitril is a neprilysin inhibitor marketed in India, mainly as a combination with valsartan, and is used in cardiovascular disease. The TxGNN model predicts it may be effective for diabetic nephropathy, supported by 1 Phase 4 clinical trial and 15 publications, most of them preclinical studies or reviews.
Note: the top-ranked TxGNN prediction is a rare COL4A1-related small vessel disease. It has no relevant supporting evidence, so this report focuses on diabetic nephropathy, the best-supported prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Brain small vessel disease 1 with or without ocular anomalies |
| TxGNN Prediction Score | 0.9958 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (15 of 15) – CDSCO approval status is not included in this data |
| Number of Listed Products | 15 (valid: 15) |
| Recommended Decision | Hold (research question; see conclusion) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on the literature, sacubitril is a prodrug whose active metabolite inhibits neprilysin, an enzyme that breaks down natriuretic peptides (ANP/BNP). It is usually given with valsartan, an angiotensin receptor blocker.
Diabetic nephropathy is driven by glomerular hypertension, oxidative stress, inflammation and fibrosis. Raising natriuretic peptides while blocking the renin-angiotensin system could plausibly act on these pathways. Several rodent studies (db/db mice, Zucker obese rats, diabetic rats) report less glomerular and tubular injury with sacubitril/valsartan. These effects were linked to reduced NF-κB inflammation, NLRP3 inflammasome activity and oxidative stress. Compared with valsartan alone, the results were not uniform: one mouse study reported differing effects between models.
In humans, a secondary analysis of the PARADIGM-HF trial examined renal function in patients with type 2 diabetes and heart failure. This provides supportive context, but it is not direct proof of benefit in diabetic nephropathy.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06501651 | Phase 4 | Unknown | 297 | Randomized, controlled, multicenter 12-week study (2:1) of sacubitril/valsartan vs valsartan in essential hypertension with type 2 diabetic nephropathy (Hyper-Save). No results available. |
The other predicted indications have no registered clinical trials.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29661699 | 2018 | Secondary analysis of RCT (PARADIGM-HF) | Lancet Diabetes Endocrinol | Effect of neprilysin inhibition on renal function in type 2 diabetes with chronic heart failure |
| 37549515 | 2023 | Clinical study (randomized groups) | Int Immunopharmacol | 112 diabetic nephropathy patients with hypertension; nifedipine plus sacubitril/valsartan vs nifedipine plus valsartan |
| 40416927 | 2025 | Clinical imaging study | Diabetes Metab Syndr Obes | BOLD-MRI assessment of renal protection by sacubitril/valsartan in type 2 diabetes |
| 37625003 | 2023 | Review | Diabetes Care | Update on the pillars of therapy to slow diabetic nephropathy progression |
| 35165832 | 2022 | Review | Curr Hypertens Rep | Newer drugs for blood pressure and hypertensive target organ damage, including diabetic kidney disease |
| 35992034 | 2022 | Preclinical (rat) | Diabetes Metab Syndr Obes | Slowed early diabetic nephropathy via NLRP3 inflammasome inhibition |
| 36589853 | 2022 | Preclinical (mouse) | Front Endocrinol | Improved diabetic kidney disease and regulated gut microbiota |
| 32596035 | 2020 | Preclinical (rat) | PeerJ | Reduced oxidative stress, NF-κB inflammation and glomerulosclerosis |
| 33870733 | 2021 | Preclinical (mouse) | Am J Physiol Renal Physiol | Differing effects vs valsartan in db/db and KKAy mice |
| 30909895 | 2019 | Preclinical (rat) | Cardiovasc Diabetol | Attenuated glomerular and tubular injury in Zucker obese rats |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 34010 | CIDMUS 100mg Tablet (Dr Reddy’s) | Strip of 14 tablets | Not stated |
| 150736 | Neptaz 200mg Tablet (Mankind Pharma) | Strip of 7 tablets | Not stated |
| 233244 | Vymada 100mg Tablet (Novartis India) | Strip of 14 tablets | Not stated |
| 358 | Azmarda 200mg Tablet (J B Chemicals) | Strip of 7 tablets | Not stated |
| 233474 | Valsac 100 Tablet (Natco Pharma) | Bottle of 28 tablets | Not stated |
There are 15 valid registrations in total, all oral tablets, and none are cancelled.
Review correction (2026-11-06): Originally stated: “There are 15 valid single-ingredient registrations in total, all oral tablets, and none are cancelled.” Removed: it described the products as single-ingredient or combination products in a way that did not match the Indian medicine data (the Indian Medicine Dataset as of 2026-11-06). Source: Indian Medicine Dataset.
Safety Considerations
- Drug Interactions: Six moderate-level interactions were identified: nitisinone, rosuvastatin, simvastatin, cobicistat, revefenacin and alpelisib.
For other safety information, please refer to the package insert. Known class effects of sacubitril/valsartan (hypotension, hyperkalaemia, changes in kidney function) would need monitoring in a diabetic nephropathy population.
Conclusion and Next Steps
Decision: Hold (research question)
Rationale: Diabetic nephropathy is the only prediction with meaningful support, but the evidence is L3: mostly animal studies and reviews, plus one Phase 4 trial with unknown status and no results. The other four predictions (brain small vessel disease, the familial hematuria syndrome, rheumatoid arthritis and hemoglobinopathy) are model output only, with no relevant clinical or mechanistic evidence.
To proceed, the following is needed:
- Results or status confirmation for NCT06501651, and ideally an adequately powered Phase 3 RCT with renal outcomes (eGFR decline, albuminuria)
- Mechanism of action data and package insert warnings and contraindications for the Indian market products
- A safety plan covering hypotension, hyperkalaemia and renal function monitoring in diabetic patients
- Confirmation of the approved indications for the Indian registrations
Review Log
Below is the review log for this page: statements checked against official Indian medicine data (the Indian Medicine Dataset used by this site). Corrections are limited to basic factual statements; model predictions, evidence levels, and conclusions were not rewritten.
| Review date | Item | Action | Source |
|---|---|---|---|
| 2026-11-06 | Removed: “single-ingredient” | Corrected | Indian Medicine Dataset |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.