Insulin Degludec

證據等級: L5

預測適應症: 6 個

Insulin Degludec: From Diabetes Mellitus to Type 1 Diabetes Mellitus

One-Sentence Summary

Insulin degludec is an ultra-long-acting basal insulin analog with an established global indication of diabetes mellitus (type 1 and type 2). The TxGNN model flags Type 1 Diabetes Mellitus as its top-ranked predicted indication, and the evidence base — 50 clinical trials and 20 publications — confirms this is not a novel repurposing signal but the drug's own core, label indication in a market (Finland) where it is not currently marketed.

Quick Overview

Item	Content
Original Indication	Diabetes mellitus (type 1 and type 2) — established global label use; no Finland-specific license record exists in this Evidence Pack
Predicted New Indication	Type 1 Diabetes Mellitus
TxGNN Prediction Score	99.44%
Evidence Level	L1
Finland Market Status	Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Insulin degludec is an ultra-long-acting basal insulin analog that acts directly on the insulin receptor, replacing the endogenous insulin that patients with type 1 diabetes lose to autoimmune β-cell destruction. Its multihexamer subcutaneous depot slowly and continuously releases monomeric insulin, giving a flat, ultra-long action profile with lower day-to-day variability than first-generation basal insulins (glargine, detemir).

Because this mechanism is direct replacement therapy rather than an indirect or inferred pathway, the TxGNN prediction of "type 1 diabetes mellitus" is not really a repurposing hypothesis — it is the drug's own established, on-label indication, already approved for T1DM in numerous markets worldwide (e.g., as Tresiba). The "Not Marketed" status recorded for this evaluation should be read as this drug not yet having Finland market authorization, not as an unvalidated new-use signal. Practically, this candidate should be tracked as a market-access case (bringing an already-proven therapy to a new market) rather than a traditional evidence-generation repurposing case.

The five other TxGNN-predicted indications for this drug (autoimmune oophoritis, opsismodysplasia, thiamine-responsive dysfunction syndrome, and two stiff-person-syndrome variants) all score highly on the model but have zero supporting trials or literature and were placed on Hold — their similarity to T1DM in the underlying knowledge graph (shared autoimmune or endocrine nodes) does not reflect an actual pharmacological rationale for insulin degludec.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00992537	Phase 1	Completed	27	Head-to-head PK/PD comparison of IDegAsp (NN5401), insulin degludec (NN1250), and insulin aspart in T1D
NCT05413369	Phase 3	Completed	582	iGlarLixi vs. IDegAsp in Chinese T2DM inadequately controlled on oral agents
NCT02030600	Phase 3	Completed	721	SWITCH 2 — randomized double-blind crossover comparing degludec vs. glargine safety/efficacy, with/without OADs
NCT05463744	Phase 3	Completed	692	Weekly insulin efsitora alfa vs. degludec in T1D on multiple daily injections
NCT05243628	Phase 4	Completed	33	Afrezza inhaled mealtime insulin + automated insulin pump or degludec in adult T1D
NCT02536859	Phase 1	Completed	60	Steady-state PK/PD crossover, degludec vs. glargine U300, in T1D
NCT05767255	Phase 3	Unknown	66	Hypoglycemia risk during inpatient-to-outpatient transition, basal-bolus vs. degludec/liraglutide
NCT01959529	Phase 3	Completed	7,637	DEVOTE — cardiovascular safety of degludec vs. glargine in T2D patients at high CV risk
NCT02500706	Phase 3	Completed	1,108	Faster-acting insulin aspart vs. NovoRapid, both combined with degludec, in adult T1D
NCT03214367	Phase 3	Completed	1,392	PRONTO-T1D — LY900014 vs. insulin lispro, combined with glargine or degludec, in adult T1D

Literature Evidence

PMID	Year	Type	Journal	Key Findings
36623517	2023	RCT	Lancet Diabetes Endocrinol	EXPECT trial — degludec vs. detemir (both + aspart) in pregnant women with T1D, non-inferiority design
37863084	2023	RCT	Lancet	ONWARDS 6 — weekly insulin icodec vs. daily degludec in a basal-bolus regimen for T1D
39270686	2024	RCT	Lancet	QWINT-5 — weekly insulin efsitora alfa vs. daily degludec, phase 3 non-inferiority in T1D
36763996	2022	Review/Meta-analysis	Clinical Therapeutics	Systematic review/meta-analysis of degludec efficacy and tolerability vs. other long-acting basal insulins in T1D and T2D
34643020	2022	RCT	Diabetes Obes Metab	HypoDeg — randomized crossover, degludec vs. glargine U100 in T1D prone to nocturnal severe hypoglycemia
36610544	2023	RCT	Diabetes Res Clin Pract	INEOX — single-center RCT comparing degludec 100 IU/mL vs. glargine 300 IU/mL efficacy/safety in T1D
34763071	2022	RCT	Endocr Pract	BIGLEAP — open-label randomized crossover, basal degludec vs. aspart via pump in T1D
36516429	2023	RCT	Diabetes Technol Ther	ULTRAFLEXI-1 — randomized crossover comparing glargine U300 vs. degludec around spontaneous exercise in T1D
31055056	2020	Review	Diabetes Metab	Current status of degludec in T1D and T2D based on randomized and observational trials
37290466	2023	Review	Lancet Diabetes Endocrinol	Management of T1D in pregnancy, including basal insulin choice and glycemic targets

Finland Market Information

No marketing authorizations are on file for insulin degludec in Finland (market_status: 未上市 / Not Marketed; total_licenses: 0). Fimea product-level license data (product name, dosage form, approved indication text) has not yet been retrieved for this candidate.

Safety Considerations

Please refer to the package insert for safety information. No structured Fimea/TFDA warnings, contraindications, or drug-interaction data are currently available for insulin degludec in this Evidence Pack (this is flagged as a Blocking data gap — DG001).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Insulin degludec's efficacy and safety in type 1 diabetes are supported by an extensive, mature evidence base — including multiple completed Phase 3 RCTs (SWITCH 2, DEVOTE, PRONTO-T1D, QWINT-5, ONWARDS 6) and systematic reviews — meeting L1 evidence criteria. However, this is not a novel repurposing signal: it is the drug's own core indication, currently unregistered in Finland, and the Blocking safety data gap (no Fimea package-insert warnings/contraindications) must be closed before any S1 safety review can proceed.

To proceed, the following is needed:

Fimea package-insert data (warnings, contraindications, DDI) — currently a Blocking data gap (DG001)
Formal DrugBank-sourced mechanism-of-action documentation (DG002)
Confirmation of the appropriate regulatory pathway for Finland market entry (likely standard marketing-authorization/mutual-recognition route, not an experimental repurposing pathway, given this is an established global indication)
Note: the five other TxGNN-predicted indications for this drug (autoimmune oophoritis, opsismodysplasia, thiamine-responsive dysfunction syndrome, classic and focal stiff-person/stiff-limb syndrome) have no supporting trials or literature and remain on Hold.
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.