Insulin Degludec
| Evidence Level: L1 | Predicted Indications: 6 |
Table of Contents
Insulin Degludec: From Diabetes Mellitus to Type 1 Diabetes Mellitus
One-Sentence Summary
Insulin degludec is an ultra-long-acting basal insulin analogue marketed in the US as Tresiba for diabetes treatment. The TxGNN model predicts it is effective for type 1 diabetes mellitus. This is an established, on-label use rather than true repurposing. The prediction is supported by 47 registered clinical trials and 20 publications, including several Phase 3 randomized trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the source data (all license indication fields are blank); basal insulin therapy for diabetes mellitus |
| Predicted New Indication | Type 1 diabetes mellitus |
| TxGNN Prediction Score | 99.44% |
| Evidence Level | L1 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 11 (all under BLA203314) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the source record. Based on known pharmacology, insulin degludec is a basal insulin analogue that binds the insulin receptor. After subcutaneous injection it is absorbed slowly and continuously, giving an ultra-long, stable action profile.
In type 1 diabetes, endogenous insulin is missing, and basal insulin replacement is the core of therapy. The mechanism therefore fits the predicted indication directly. The high TxGNN score is consistent with this known drug-disease relationship.
The source record has empty original-indication and mechanism fields. These are missing data, not a novel finding. The labeled indication should be confirmed against current regulatory documents.
Clinical Trial Evidence
The Evidence Pack lists 47 trials. The table shows the 10 most relevant to type 1 diabetes. In several of them, degludec is the background or comparator insulin rather than the main intervention.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02500706 | Phase 3 | Completed | 1108 | Faster-acting insulin aspart vs NovoRapid, both combined with degludec, in adults with T1D |
| NCT03214367 | Phase 3 | Completed | 1392 | PRONTO-T1D: LY900014 vs insulin lispro, combined with glargine or degludec, in adults with T1D |
| NCT05904743 | Phase 4 | Completed | 141 | INHALE-3: inhaled insulin (Afrezza) plus degludec vs usual care in adults with T1D |
| NCT03838783 | Phase 4 | Unknown | 30 | Degludec plus insulin pump in an untethered regimen in exercising T1D patients |
| NCT02536859 | Phase 1 | Completed | 60 | Steady-state PD/PK of degludec vs insulin glargine 300 U/mL in T1D (double-blind crossover) |
| NCT01868529 | Phase 1 | Completed | 63 | Pharmacodynamic response of insulin degludec vs insulin glargine at steady state in T1D |
| NCT05069545 | N/A (observational) | Completed | 411 | Glycaemic control in T1D using the NovoPen 6 smart pen with Tresiba and Fiasp |
| NCT02662114 | N/A (observational) | Completed | 2302 | EU-TREAT: retrospective effectiveness of Tresiba after basal insulin switch in T1D or T2D |
| NCT03557892 | N/A | Completed | 28 | Crossover of insulin pump plus CGM vs multi-injection therapy with degludec as basal insulin in T1D |
| NCT02360254 | N/A (observational) | Completed | 26 | Effects of switching from twice-daily glargine or detemir to once-daily degludec in T1D |
One trial (NCT02030600, SWITCH 2, Phase 3, 721 participants) was graded “A” in the source data. It actually enrolled type 2 diabetes patients, so it does not count as direct T1D evidence.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36623517 | 2023 | RCT | Lancet Diabetes Endocrinol | EXPECT: non-inferiority trial of degludec vs detemir (both with aspart) in pregnant women with T1D |
| 37863084 | 2023 | RCT | Lancet | ONWARDS 6: once-weekly icodec vs once-daily degludec in adults with T1D (phase 3a) |
| 39270686 | 2024 | RCT | Lancet | QWINT-5: once-weekly efsitora alfa vs once-daily degludec in adults with T1D (phase 3) |
| 34643020 | 2022 | RCT | Diabetes Obes Metab | HypoDeg: crossover trial of degludec vs glargine U100 for nocturnal hypoglycaemia in T1D |
| 36516429 | 2023 | RCT | Diabetes Technol Ther | ULTRAFLEXI-1: glargine 300 U/mL vs degludec 100 U/mL around spontaneous exercise in T1D |
| 34763071 | 2022 | RCT | Endocr Pract | BIGLEAP: degludec vs pump-delivered aspart in well-controlled T1D (crossover) |
| 36610544 | 2023 | RCT | Diabetes Res Clin Pract | INEOX: efficacy and safety of degludec 100 IU/mL vs glargine 300 IU/mL in adults with T1D |
| 36800034 | 2023 | Randomized study | Eur J Pediatr | Degludec and glargine vs NPH insulin in toddlers and preschoolers with T1D (60 children) |
| 36763996 | 2022 | Meta-analysis | Clin Ther | Efficacy and tolerability of degludec vs other long-acting basal analogues in T1D and T2D |
| 29477399 | 2018 | Network meta-analysis | Value Health | Relative efficacy and safety of basal insulin regimens in adults with T1D |
US Market Information
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| BLA203314 | Tresiba | Injection, solution | Novo Nordisk |
| BLA203314 | Insulin Degludec | Injection, solution | Novo Nordisk Pharma, Inc. |
| BLA203314 | Insulin Degludec | Injection, solution | A-S Medication Solutions |
| BLA203314 | Tresiba | Injection, solution | Novo Nordisk |
| BLA203314 | TRESIBA | Injection, solution | A-S Medication Solutions |
The approved-indication text is blank in the source data.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Degludec is already marketed and has direct T1D randomized evidence, including EXPECT, HypoDeg, INEOX and the Phase 3 comparator trials ONWARDS 6 and QWINT-5. The evidence is strong, but the prediction is an on-label use rather than a novel repurposing. Safety and label data are missing from the record.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- Confirmation of the labeled indication from current regulatory documents
- Mechanism of action data, to fill the empty MOA field
- Correction of the trial relevance grading (NCT02030600 is a T2D trial)
The other five predicted indications (autoimmune oophoritis, opsismodysplasia, thiamine-responsive dysfunction syndrome, classic stiff person syndrome, focal stiff limb syndrome) have no trials or literature. They are L5 and should be on Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.