Insulin Degludec
| Evidence Level: L5 | Predicted Indications: 5 |
Table of Contents
Insulin Degludec: Autoimmune oophoritis
One-Sentence Summary
Insulin degludec is an ultra-long-acting basal insulin analogue, originally used to treat diabetes mellitus and diabetic ketoacidosis. The TxGNN model predicts it may be effective for autoimmune oophoritis. The data compiled for this report include more than 40 registered clinical trials and 19 publications supporting this use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Autoimmune oophoritis |
| TxGNN Prediction Score | 0.9923 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not 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 replaces deficient endogenous insulin. In type 1 diabetes, the body produces little or no insulin, so basal insulin replacement is the foundation of treatment.
The predicted indication sits within the drug’s original indication of diabetes mellitus. The very high TxGNN score is consistent with this established mechanism. The product registered in Australia (Ryzodeg) is a co-formulation of insulin degludec and insulin aspart (70/30). The trial evidence below covers both degludec alone and the degludec/aspart co-formulation.
Clinical Trial Evidence
More than 40 trials are listed. The 10 most relevant are shown below, prioritising late-phase, completed trials with degludec as the direct subject or comparator.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02034513 | Phase 3 | Completed | 501 | SWITCH 1: degludec vs insulin glargine, both with insulin aspart, in a double-blind crossover in type 1 diabetes |
| NCT00978627 | Phase 3 | Completed | 548 | Degludec/aspart (IDegAsp) once daily plus aspart vs insulin detemir plus aspart over 26 weeks, with extension |
| NCT01835431 | Phase 3 | Completed | 362 | IDegAsp once daily plus aspart vs insulin detemir plus aspart in children and adolescents |
| NCT02500706 | Phase 3 | Completed | 1108 | Faster-acting aspart vs NovoRapid, both with degludec, in adults (degludec as background basal) |
| NCT02670915 | Phase 3 | Completed | 834 | Faster-acting aspart vs NovoRapid, both with degludec, in children and adolescents (degludec as background basal) |
| NCT05463744 | Phase 3 | Completed | 692 | Once-weekly efsitora alfa vs degludec with multiple daily injections |
| NCT01569841 | Phase 3 | Completed | 24 | Degludec vs glargine on glycaemic control using continuous glucose monitoring |
| NCT00612040 | Phase 2 | Completed | 178 | Two degludec formulations vs glargine, all with aspart, over 16 weeks |
| NCT04075513 | Phase 4 | Completed | 343 | Glargine 300 U/mL vs degludec on time in range and variability by continuous glucose monitoring |
| NCT05904743 | Phase 4 | Completed | 141 | INHALE-3: inhaled insulin plus degludec vs usual care in adults |
Further trials include Phase 1 pharmacodynamic studies, real-world observational studies (for example NCT02392117, with 1262 participants) and post-marketing surveillance studies of Ryzodeg in Korea (NCT03416855) and India (NCT02230618).
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36623517 | 2023 | RCT | Lancet Diabetes Endocrinol | EXPECT: degludec vs detemir (with aspart) in pregnant women with type 1 diabetes, non-inferiority design |
| 37863084 | 2023 | RCT | Lancet | ONWARDS 6: once-weekly icodec vs once-daily degludec in adults with type 1 diabetes |
| 39270686 | 2024 | RCT | Lancet | QWINT-5: once-weekly efsitora alfa vs degludec in adults with type 1 diabetes |
| 36763996 | 2022 | Systematic review and meta-analysis | Clin Ther | Efficacy and tolerability of degludec vs other long-acting basal analogues in type 1 and type 2 diabetes |
| 40627908 | 2025 | Systematic review and meta-analysis | J Diabetes Complications | Degludec vs efsitora in type 1 and type 2 diabetes |
| 33662147 | 2021 | Systematic review | Cochrane Database Syst Rev | (Ultra-)long-acting insulin analogues in type 1 diabetes |
| 29477399 | 2018 | Systematic review and network meta-analysis | Value Health | Relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes |
| 27181070 | 2016 | Post hoc analysis | J Diabetes Investig | IDegAsp in Japanese patients with type 1 diabetes: distinct prandial and basal glucose-lowering effects |
| 23620200 | 2013 | Review | Drugs | Degludec and degludec/aspart in the management of diabetes mellitus |
| 30789066 | 2019 | Review | Expert Opin Drug Metab Toxicol | Potential use of the degludec/aspart premix in type 1 diabetes |
Of note, a 2025 study (PMID 40903851, Diabetes Obes Metab) examined early degludec with intravenous insulin infusion in diabetic ketoacidosis, which relates to the drug’s other listed original indication.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11426J | Ryzodeg Penfill | Injection, cartridges, 70 units-30 units per mL, 3 mL, 5 | Not recorded in the data compiled |
Safety Considerations
- Drug Interactions: 351 known interactions were identified. Examples rated Moderate include:
- Other antidiabetic agents: metformin, pioglitazone, alogliptin, albiglutide
- Sympathomimetics and beta-agonists: epinephrine, salbutamol, formoterol, phenylephrine, pseudoephedrine
- Beta-blocker: acebutolol
- Corticosteroid: hydrocortisone (systemic)
- Hormonal agents: estradiol, levonorgestrel, norethisterone
- Other: hydrochlorothiazide, doxycycline, alpelisib, ethanol
Topical corticosteroids (hydrocortisone and alclometasone) are rated Minor.
Please refer to the TGA-approved Product Information (PI) for warnings and contraindications.
Other Predicted Indications
Five further predictions were ranked lower, all with no clinical trials or literature (L5) and a recommendation of Hold:
| Predicted Indication | TxGNN Score | Comment |
|---|---|---|
| Autoimmune oophoritis | 0.9923 | No plausible direct link to basal insulin replacement |
| Opsismodysplasia | 0.9912 | Speculative link via insulin signalling (INPPL1/SHIP2); exogenous insulin is not expected to correct a genetic defect |
| Thiamine-responsive dysfunction syndrome | 0.9910 | Insulin could manage associated diabetes symptomatically only |
| Classic stiff person syndrome | 0.9908 | Likely reflects shared anti-GAD autoimmunity with type 1 diabetes; insulin does not treat the neurological disease |
| Focal stiff limb syndrome | 0.9908 | As above |
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 trials and several systematic reviews support insulin degludec in type 1 diabetes. This is an on-label use, so the main task is confirming the Australian product’s labelled use rather than demonstrating new efficacy.
To proceed, the following is needed:
- The approved indication text for ARTG 11426J, which is blank in the data compiled. Confirm that type 1 diabetes is covered by the Ryzodeg registration, since the trials above largely involve degludec alone.
- Warnings and contraindications from the TGA Product Information, as this safety data was not available.
- Mechanism of action data (for example from DrugBank).
- A hypoglycaemia monitoring plan, individualised dosing, and a review of interacting medicines (351 known interactions).
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.