Insulin Degludec

證據等級: L5

預測適應症: 10 個

Insulin Degludec: From Diabetes Management to Type 1 Diabetes Mellitus

One-Sentence Summary

Insulin degludec (Tresiba®) is an ultra-long-acting basal insulin analog approved globally for the management of diabetes mellitus in adults and children, though it is currently not registered in Taiwan. The TxGNN model predicts it may be effective for Type 1 Diabetes Mellitus, with 50 clinical trials and 20 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not registered in Taiwan
Predicted New Indication	Type 1 Diabetes Mellitus
TxGNN Prediction Score	99.44%
Evidence Level	L1
Taiwan Market Status	Not Marketed
Number of Authorizations	0 (Taiwan)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Insulin degludec is a second-generation ultra-long-acting basal insulin analog. Although formal mechanism of action data was not retrieved in this Evidence Pack, based on its well-established pharmacological profile, insulin degludec works by binding to insulin receptors in peripheral target tissues—primarily skeletal muscle and adipose tissue—promoting glucose uptake and suppressing hepatic glucose production. After subcutaneous injection, it forms soluble multi-hexamers that slowly dissociate into monomers, producing a flat and stable absorption curve with a duration of action exceeding 42 hours. Compared to first-generation analogs such as insulin glargine and insulin detemir, insulin degludec demonstrates approximately 20% lower pharmacodynamic variability (coefficient of variation), translating to more predictable glycemic control and a significantly reduced risk of nocturnal hypoglycemia.

Type 1 Diabetes Mellitus is caused by autoimmune destruction of pancreatic β-cells, resulting in absolute insulin deficiency. Insulin replacement is not merely a treatment option—it is a survival necessity for T1DM patients. Insulin degludec directly addresses this core pathophysiology by providing stable, long-duration basal insulin coverage. Its ultra-flat action profile is particularly advantageous in T1DM, where day-to-day glycemic variability is inherently high and hypoglycemia risk is a major concern.

The TxGNN prediction score of 99.44% reflects this direct and mechanistically unambiguous link. Importantly, this prediction is not a speculative repurposing signal: insulin degludec is already approved for T1DM in the European Union, United States, and Japan. The high confidence score is consistent with the model correctly identifying an established yet Taiwan-unregistered therapeutic application. Proceeding with this prediction is therefore less about de novo drug development and more about addressing a regulatory gap in the Taiwan market.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT05463744	Phase 3	Completed	692	Once-weekly insulin efsitora alfa (LY3209590) compared with once-daily insulin degludec in T1DM patients on MDI therapy; insulin degludec served as the gold-standard active comparator, confirming its benchmark efficacy and safety role in T1DM
NCT02034513	Phase 3	Completed	501	SWITCH 1: double-blind crossover RCT comparing insulin degludec vs. insulin glargine, both combined with mealtime insulin aspart, in T1DM adults; demonstrated non-inferior HbA1c reduction with significantly lower hypoglycemia rates favouring degludec
NCT03214367	Phase 3	Completed	1,392	PRONTO-T1D: randomized double-blind RCT of LY900014 vs. insulin lispro in T1DM, both administered in combination with either insulin glargine or insulin degludec as basal insulin; confirmed degludec’s efficacy as a basal component in T1DM regimens
NCT01835431	Phase 3	Completed	362	Phase 3 trial investigating insulin degludec/insulin aspart (IDegAsp, once daily + aspart for remaining meals) vs. insulin detemir in children and adolescents with T1DM; demonstrated comparable glycemic control with a favourable safety profile in paediatric populations
NCT03328845	Phase 4	Completed	300	INEOX study: evaluated oxidative stress parameters across different current insulin analogs in T1DM patients; provided mechanistic safety data on degludec’s metabolic footprint beyond glycemic endpoints
NCT02192450	Phase 4	Completed	149	Assessed whether insulin degludec reduces the risk of symptomatic nocturnal hypoglycemia compared to insulin glargine in T1DM patients at high risk of severe nocturnal hypoglycemia; confirmed clinically meaningful benefit in this high-risk subgroup
NCT00612040	Phase 2	Completed	178	Early foundational treat-to-target trial comparing two insulin degludec (NN1250) formulations vs. insulin glargine in a basal-bolus regimen in T1DM adults; established dose-finding and initial efficacy/safety basis for degludec in T1DM
NCT00841087	Phase 2	Completed	65	Japanese exploratory Phase 2 study assessing safety (with emphasis on hypoglycemia) of insulin degludec + NovoRapid in T1DM patients switching from long-acting insulin in a basal-bolus regimen; provided early Asian-specific safety data
NCT04409587	Phase 4	Completed	59	BIGLEAP: investigator-initiated crossover trial comparing once-daily insulin degludec injection vs. CSII basal delivery in T1DM, both with bolus aspart via pump; assessed glycemic variability, overall control, and hypoglycemia incidence via CGM
NCT03463564	Phase 4	Recruiting	150	METRO study: comparing insulin pump vs. multiple daily injections (including degludec as basal insulin) in T1DM adolescents transitioning to adult care; evaluating glycemic and metabolic outcomes in this high-risk transition period

Literature Evidence

PMID	Year	Type	Journal	Key Findings
37863084	2023	RCT	Lancet	ONWARDS 6: Phase 3a RCT comparing once-weekly insulin icodec vs. once-daily insulin degludec in T1DM adults on basal-bolus regimen; degludec as active comparator confirmed its standard-of-care status in T1DM
39270686	2024	RCT	Lancet	QWINT-5: Phase 3 non-inferiority RCT of once-weekly insulin efsitora alfa vs. insulin degludec in T1DM adults; insulin degludec again served as the benchmark comparator, validating its established role
36623517	2023	RCT	Lancet Diabetes & Endocrinology	EXPECT trial: first dedicated RCT comparing degludec vs. insulin detemir (both with insulin aspart) in pregnant women with T1DM; demonstrated non-inferiority with comparable maternal and neonatal safety profiles
36763996	2022	Systematic Review / Meta-analysis	Clinical Therapeutics	Meta-analysis comparing degludec vs. insulin glargine and detemir in T1DM and T2DM; confirmed comparable HbA1c reduction with statistically significant reductions in overall and nocturnal hypoglycemia favouring degludec
29477399	2018	Systematic Review	Value in Health	Network meta-analysis of basal insulin regimens in T1DM adults; positioned insulin degludec favourably relative to other long-acting analogs for hypoglycemia risk reduction and glycemic stability
31055056	2020	Evidence-based Review	Diabetes & Metabolism	Comprehensive review of randomized controlled and observational studies; documented superior fasting plasma glucose control and consistent nocturnal hypoglycemia reductions with degludec across both T1DM and T2DM real-world settings
25081590	2014	Meta-analysis	Diabetes Therapy	Patient-level meta-analysis across seven Phase 3a trials comparing degludec vs. insulin glargine in T1DM and T2DM; established the consistent advantage in nocturnal hypoglycemia with non-inferior overall glycemic control
35476308	2022	Systematic Review	International Journal of Clinical Pharmacy	Indirect treatment comparison of degludec U100 vs. insulin glargine U300 in T1DM; evaluated safety, efficacy, and cost-effectiveness differences to support formulary decision-making
23890782	2014	Narrative Review	Endocrinología y Nutrición	Early clinical review summarizing the pharmacological rationale for degludec (soluble multi-hexamer formation, ultra-long flat action profile) and key clinical outcomes from T1DM and T2DM development trials
40098468	2025	RCT Extension	Diabetes Technology & Therapeutics	INHALE-3 extension: 30-week study of inhaled technosphere insulin combined with insulin degludec in T1DM adults; confirmed sustained HbA1c and time-in-range benefits with degludec as the basal component in a novel combination regimen

Safety Considerations

Please refer to the SmPC for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Insulin degludec has robust Phase 3 RCT evidence—including multiple completed head-to-head trials directly in T1DM populations—and is approved by the EMA, FDA, and PMDA. The Taiwan non-registration represents a regulatory gap, not an evidence gap, and the clinical evidence fully supports a market authorization application with TFDA.

To proceed, the following is needed:

Taiwan safety documentation: Obtain and parse the full prescribing information (global SmPC / package insert) to document key warnings, contraindications, and clinically relevant drug interactions required for local regulatory submission
Mechanism of action dossier: Retrieve the complete DrugBank entry (DB09564) to formally document pharmacodynamic and pharmacokinetic properties for the TFDA regulatory file
TFDA market access pathway assessment: Evaluate the applicable submission route (e.g., abbreviated NDA based on existing EMA/FDA approvals), estimate timeline, and assess National Health Insurance reimbursement positioning against currently listed basal insulin analogs
Local clinical needs assessment: Review whether any Taiwan-specific population data (e.g., East Asian PK differences, local hypoglycemia risk profiles) would be requested by TFDA reviewers
Pharmacovigilance plan: Design a post-marketing surveillance framework aligned with TFDA requirements to monitor hypoglycemia events and injection-site reactions in the local population
Disclaimer

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