Insulin Degludec
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Insulin Degludec: From Diabetes Mellitus to Type 1 Diabetes Mellitus
One-Sentence Summary
Insulin degludec is a long-acting basal 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 on-label use that overlaps with the original indication, so it is not a true repurposing case.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Diabetes mellitus; diabetic ketoacidosis (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Type 1 diabetes mellitus |
| TxGNN Prediction Score | 99.44% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| 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 general pharmacological knowledge, insulin degludec is an ultra-long-acting basal insulin analogue. It binds the insulin receptor and replaces deficient endogenous insulin, giving a flat, stable glucose-lowering profile.
Type 1 diabetes is defined by absolute insulin deficiency, so basal insulin replacement is the standard of care. The predicted indication falls directly within the original indication of diabetes mellitus. The high TxGNN score is therefore consistent with known pharmacology rather than being a novel discovery.
Other diseases in the prediction list (for example autoimmune oophoritis, stiff person syndrome and localized lipodystrophy) have no supporting trials or literature. Their associations most likely reflect graph links through type 1 diabetes comorbidity, and they are not assessed further here.
Clinical Trial Evidence
The data include 40 trials in type 1 diabetes, many of them Phase 1 pharmacodynamic studies. The table lists the 10 most relevant, favouring direct degludec studies with the largest enrollments.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02034513 | Phase 3 | Completed | 501 | SWITCH 1: degludec vs glargine, both with insulin aspart, double-blind cross-over in type 1 diabetes |
| NCT05463744 | Phase 3 | Completed | 692 | Once-weekly efsitora vs degludec in type 1 diabetes on multiple daily injections |
| NCT01835431 | Phase 3 | Completed | 362 | Degludec/aspart once daily vs detemir in children and adolescents with type 1 diabetes |
| NCT00978627 | Phase 3 | Completed | 548 | BOOST T1: degludec/aspart plus aspart vs detemir plus aspart in type 1 diabetes |
| NCT02500706 | Phase 3 | Completed | 1108 | Faster-acting aspart vs NovoRapid, both with degludec, in adults with type 1 diabetes |
| NCT02670915 | Phase 3 | Completed | 834 | Faster-acting aspart vs NovoRapid, both with degludec, in children and adolescents |
| NCT00612040 | Phase 2 | Completed | 178 | Two degludec formulations vs glargine in a basal/bolus regimen over 16 weeks |
| NCT04075513 | Phase 4 | Completed | 343 | Glargine 300 U/ml vs degludec 100 U/ml: glucose in target range and variability on CGM |
| NCT01569841 | Phase 3 | Completed | 24 | Degludec vs glargine on glycaemic control using continuous glucose monitoring |
| NCT05434559 | N/A | Completed | 475 | Retrospective study of glycaemic control after switching to degludec in adults with type 1 diabetes |
Note: Phase 3 trials with faster-acting aspart, LY900014 or other insulins use degludec as background or comparator therapy, so they are indirect evidence for degludec itself.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36623517 | 2023 | RCT | Lancet Diabetes Endocrinol | EXPECT: degludec vs detemir, both with aspart, in pregnant women with type 1 diabetes (non-inferiority) |
| 39270686 | 2024 | RCT | Lancet | QWINT-5: once-weekly efsitora vs once-daily degludec in adults with type 1 diabetes |
| 37863084 | 2023 | RCT | Lancet | ONWARDS 6: once-weekly icodec vs once-daily degludec in type 1 diabetes |
| 40903851 | 2025 | RCT | Diabetes Obes Metab | Early degludec added to intravenous insulin infusion in diabetic ketoacidosis |
| 36763996 | 2022 | Meta-analysis | Clin Ther | Efficacy and tolerability of degludec vs other long-acting basal analogues in type 1 and 2 diabetes |
| 40627908 | 2025 | Meta-analysis | J Diabetes Complications | Degludec vs efsitora in type 1 and type 2 diabetes |
| 33662147 | 2021 | Cochrane review | Cochrane Database Syst Rev | (Ultra-)long-acting insulin analogues for type 1 diabetes |
| 29477399 | 2018 | Network meta-analysis | Value Health | Relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes |
| 23620200 | 2013 | Review | Drugs | Review of degludec and degludec/aspart in diabetes management |
| 35147781 | 2022 | Real-world study | Acta Diabetol | Pregnancy outcomes in women with type 1 diabetes using degludec vs other long-acting analogues |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15703P | TRESIBA® FLEXTOUCH® Solution for Injection in Pre-filled Pen 100 U/ml | Injection, solution | Not stated in the licence data |
| SIN15704P | TRESIBA® FLEXTOUCH® Solution for Injection in Pre-filled Pen 200 U/ml | Injection, solution | Not stated in the licence data |
| SIN15706P | RYZODEG® FLEXTOUCH® Solution for Injection in Pre-filled Pen 100 U/ml | Injection, solution | Not stated in the licence data |
Safety Considerations
Drug Interactions: 100 interactions were identified, and 20 are shown in the data compiled for this report. Most are rated Moderate, and a few are Minor. Notable moderate interactions include:
- Other glucose-lowering drugs: metformin, pioglitazone, alogliptin, albiglutide, alpelisib
- Sympathomimetics and beta-agonists: epinephrine, phenylephrine, pseudoephedrine, salbutamol, formoterol
- Beta-blocker: acebutolol
- Hormones and others: hydrocortisone, estradiol, levonorgestrel, norethisterone, hydrochlorothiazide, doxycycline, ethanol
Minor interactions include topical corticosteroids (hydrocortisone, alclometasone).
Localized lipodystrophy at repeated injection sites is a recognized effect of injected insulin. Rotating injection sites is the standard prevention.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several Phase 3 randomized trials, including SWITCH 1 and BOOST T1, together with randomized trials and meta-analyses in type 1 diabetes, support degludec's efficacy and safety. The indication essentially overlaps with the existing diabetes indication, and the product is already registered in Singapore. The guardrails reflect gaps in regulatory and safety data, not doubts about efficacy.
To proceed, the following is needed:
- Download and review the HSA package insert to confirm approved indications, warnings and contraindications (a blocking gap for safety screening)
- Confirm that the Singapore labels explicitly cover type 1 diabetes, since the licence data contain no indication text
- Obtain mechanism of action data from DrugBank
- Complete the relevance grading for the many trials still pending in the data
- Define monitoring for hypoglycaemia and for interactions with other glucose-lowering drugs
- Evaluate separately any use in special populations (pregnancy, children, neonates)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.