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 (supplied in New Zealand as the degludec/insulin aspart 70/30 co-formulation, Ryzodeg) is an ultra-long-acting insulin analogue originally used for diabetes mellitus and diabetic ketoacidosis. The TxGNN model predicts it may be effective for type 1 diabetes mellitus, with 40 clinical trials and 19 publications currently supporting this direction. This is essentially an established, on-label use of the drug rather than true repurposing, and the only New Zealand authorization on record is cancelled.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Diabetes mellitus; diabetic ketoacidosis (from the knowledge graph; no approved indication text is recorded in the New Zealand licence data) |
| Predicted New Indication | Type 1 diabetes mellitus |
| TxGNN Prediction Score | 99.44% |
| Evidence Level | L1 |
| New Zealand Market Status | Cancelled only |
| Number of Authorizations | 1 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the data compiled for this report. Based on known pharmacology, insulin degludec is a basal insulin analogue that binds the insulin receptor and lowers blood glucose. It has a flat, long-lasting profile, and the Ryzodeg product combines it with rapid-acting insulin aspart in a 70/30 ratio.
Type 1 diabetes is a state of absolute insulin deficiency, so insulin replacement is the cornerstone of treatment. The relationship between the original indication (diabetes mellitus) and the predicted one (type 1 diabetes) is therefore direct: type 1 diabetes is a subtype of diabetes mellitus. The very high TxGNN score agrees with this established use.
The other five predicted indications (autoimmune oophoritis, opsismodysplasia, thiamine-responsive dysfunction syndrome, classic stiff person syndrome and focal stiff limb syndrome) have no clinical trials or publications. They are computational predictions only, probably reflecting network proximity to diabetes biology (for example, shared anti-GAD autoimmunity in stiff person syndrome). They are not supported by any demonstrated mechanism and are on Hold.
Clinical Trial Evidence
The compiled data contain 40 trials in type 1 diabetes. The 10 most relevant are listed below, prioritising completed Phase 3 trials and trials with direct degludec evidence.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05463744 | Phase 3 | Completed | 692 | Once-weekly efsitora alfa vs insulin degludec in T1D on multiple daily injections (comparator to be verified against the registry record) |
| NCT02034513 | Phase 3 | Completed | 501 | SWITCH 1: degludec vs glargine, both with aspart, double-blind crossover in T1D |
| NCT00978627 | Phase 3 | Completed | 548 | Degludec/aspart once daily plus aspart vs detemir plus aspart in T1D (BOOST T1) |
| NCT01835431 | Phase 3 | Completed | 362 | Degludec/aspart vs detemir, each with mealtime aspart, in children and adolescents with T1D |
| NCT01569841 | Phase 3 | Completed | 24 | Degludec vs glargine on glycaemic control using continuous glucose monitoring in T1D |
| NCT02500706 | Phase 3 | Completed | 1108 | Faster-acting aspart vs NovoRapid, both with degludec, in adults with T1D (degludec as background basal) |
| NCT02670915 | Phase 3 | Completed | 834 | Faster-acting aspart vs NovoRapid, both with degludec, in children and adolescents with T1D (degludec as background basal) |
| NCT00612040 | Phase 2 | Completed | 178 | Two degludec formulations vs glargine, each with aspart, 16-week treat-to-target in T1D |
| NCT04075513 | Phase 4 | Completed | 343 | Glargine 300 U/ml vs degludec 100 U/ml on glucose in target range and variability (CGM) in T1D |
| NCT03838783 | Phase 4 | Unknown | 30 | Degludec with continuous subcutaneous insulin infusion during exercise in T1D |
Several additional Phase 1 pharmacodynamic studies and real-world surveillance studies (for example NCT02392117, n=1262) also support the safety and pharmacology of degludec and degludec/aspart in T1D.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37863084 | 2023 | RCT | Lancet | ONWARDS 6: once-weekly icodec vs once-daily degludec in adults with T1D (phase 3a, treat-to-target) |
| 39270686 | 2024 | RCT | Lancet | QWINT-5: once-weekly efsitora vs once-daily degludec in adults with T1D (non-inferiority) |
| 36623517 | 2023 | RCT | Lancet Diabetes Endocrinol | EXPECT: degludec vs detemir, both with aspart, in pregnant women with T1D |
| 36763996 | 2022 | Systematic review/Meta-analysis | Clin Ther | Efficacy and tolerability of degludec vs other long-acting basal analogues in T1D and T2D |
| 33662147 | 2021 | Systematic review (Cochrane) | Cochrane Database Syst Rev | (Ultra-)long-acting insulin analogues for people with T1D |
| 40627908 | 2025 | Systematic review/Meta-analysis | J Diabetes Complications | Efsitora vs degludec in T1D and T2D |
| 29477399 | 2018 | Network meta-analysis | Value Health | Relative efficacy and safety of basal insulin regimens in adults with T1D |
| 40903851 | 2025 | Clinical study (RCT) | Diabetes Obes Metab | Early degludec plus intravenous insulin infusion vs infusion alone in diabetic ketoacidosis |
| 35147781 | 2022 | Real-world cohort | Acta Diabetol | Pregnancy outcomes in women with T1D using degludec |
| 30789066 | 2019 | Review | Expert Opin Drug Metab Toxicol | Potential role of the degludec/aspart 70/30 premix in T1D |
New Zealand Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 2704471 | Ryzodeg 70/30 Penfill | Injection: degludec 70 U with insulin aspart 30 U, 100 U per ml, 3 ml | Not recorded (status: cancelled) |
Safety Considerations
- Drug Interactions: 351 interactions were recorded. Most of those listed are Moderate, and a few are Minor. Moderate interactions include:
- Other antidiabetic agents: metformin, pioglitazone, alogliptin and albiglutide (additive glucose lowering).
- Sympathomimetics and beta-agonists: epinephrine, salbutamol, formoterol, phenylephrine and pseudoephedrine.
- Beta-blocker: acebutolol.
- Corticosteroids: hydrocortisone.
- Hormonal agents: estradiol, levonorgestrel and norethisterone.
- Others: hydrochlorothiazide, doxycycline, alpelisib and ethanol.
- Topical corticosteroids (hydrocortisone, alclometasone) are Minor.
Please refer to the package insert for warnings and contraindications. Package insert information was not available for this report.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 randomised trials and several systematic reviews support insulin degludec in type 1 diabetes, so the evidence level is L1. However, this is an established use rather than new repurposing, and the only New Zealand authorization for the Ryzodeg product is cancelled. Safety label information and mechanism of action data are also missing.
To proceed, the following is needed:
- Medsafe package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data, for example from DrugBank
- Confirmation of the current New Zealand regulatory pathway, since the Ryzodeg licence is cancelled
- Verification of the comparator in NCT05463744 against the registry record
- A glucose-monitoring and hypoglycaemia plan, with attention to the moderate interactions listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.