Insulin Aspart
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Insulin Aspart: From Diabetes Mellitus to Type 1 Diabetes Mellitus
One-Sentence Summary
Insulin aspart (NovoRapid®/NovoLog®) is a rapid-acting human insulin analogue used globally for blood glucose management in diabetes mellitus, but currently not registered in Taiwan. The TxGNN model predicts it may be effective for Type 1 Diabetes Mellitus (T1DM), with 50 clinical trials and 20 publications supporting this direction — representing the highest evidence level (L1) in our pipeline. This evaluation confirms a globally-validated indication and supports a potential Taiwan regulatory filing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not registered in Taiwan (globally approved for diabetes mellitus) |
| Predicted New Indication | Type 1 Diabetes Mellitus |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L1 |
| Taiwan Market Status | Not marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in this data package. Based on known information, insulin aspart is a rapid-acting human insulin analogue in which the amino acid proline at position B28 is replaced by aspartic acid. This structural modification reduces self-aggregation, allowing faster subcutaneous absorption compared to regular human insulin. Insulin aspart is commercially available worldwide as NovoRapid® (EU/Japan) and NovoLog® (USA) and is used as a mealtime bolus insulin in both type 1 and type 2 diabetes mellitus. It is not currently registered with Taiwan’s TFDA.
Type 1 diabetes mellitus is characterised by autoimmune destruction of pancreatic beta cells, resulting in absolute insulin deficiency. Exogenous insulin replacement is the only viable treatment. The rapid onset of action of insulin aspart — approximately 10 to 20 minutes after subcutaneous injection, with a peak effect at 1 to 3 hours — closely mimics the physiological postprandial insulin surge that T1DM patients entirely lack. This pharmacokinetic advantage makes insulin aspart mechanistically ideal for T1DM management, particularly in intensive basal-bolus regimens and continuous subcutaneous insulin infusion (CSII/insulin pump) settings.
The TxGNN prediction score of 99.95% for T1DM, combined with L1 clinical evidence, reflects not a speculative repurposing hypothesis but a strong mechanistic and clinical confirmation. Insulin aspart is already the standard-of-care bolus insulin in T1DM across all major markets. For Taiwan, this evaluation primarily serves to document the evidence base for a potential new drug application (NDA) filing with TFDA.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00773279 | Phase 3 | Completed | 242 | Randomized crossover study comparing insulin detemir + insulin aspart administered via new disposable pen PDS290 versus FlexPen® in T1DM/T2DM; assessed glycaemic control, safety, and patient preference — highest-grade direct evidence for insulin aspart in T1DM |
| NCT00071448 | Phase 3 | Completed | 378 | Basal/bolus therapy with insulin aspart versus regular human insulin or insulin lispro combined with NPH in children and adolescents with T1DM (USA, 2002–2004); demonstrated safety and efficacy of insulin aspart in the paediatric T1DM population |
| NCT00095082 | Phase 3 | Completed | 447 | Insulin detemir + insulin aspart versus insulin glargine + insulin aspart in T1DM (Europe/USA); established insulin aspart as the standard bolus component in basal-bolus regimens for T1DM |
| NCT00474045 | Phase 3 | Completed | 470 | Multinational RCT comparing insulin detemir versus NPH insulin, both combined with insulin aspart, in pregnant women with T1DM; confirmed safety and efficacy of insulin aspart in T1DM during pregnancy |
| NCT07076199 | Phase 3 | Recruiting | 877 | 26-week comparison of once-weekly insulin icodec versus once-daily insulin glargine U100, both in combination with insulin aspart, in adults with T1DM; largest ongoing T1DM trial with insulin aspart as the bolus comparator arm |
| NCT03977727 | Phase 3 | Completed | 40 | Exploratory randomized crossover comparing faster-acting insulin aspart (Fiasp®) versus NovoLog® in Medtronic 670G closed-loop system in T1DM adults; supports insulin aspart use in automated insulin delivery |
| NCT00095446 | Phase 4 | Completed | 513 | Largest-sample Phase 4 study: insulin aspart versus insulin lispro, both in insulin pumps (CSII), in T1DM and insulin-requiring T2DM (USA); directly supports CSII use of insulin aspart in T1DM clinical practice |
| NCT00467649 | Phase 4 | Completed | 112 | Randomized multicenter comparison of basal insulin intensification with Symlin® versus rapid-acting insulin (including insulin aspart) in T2DM; characterized bolus intensification strategy applicable to T1DM |
| NCT01526941 | Phase 1 | Completed | 27 | Double-blind crossover PK/PD comparison of biphasic insulin aspart 30 versus biphasic insulin aspart 70 at single dose and steady state in T1DM patients (Europe); characterised pharmacodynamic profiles for formulation optimization |
| NCT01174303 | Phase 1 | Completed | 28 | Investigated pharmacodynamic exposure of insulin degludec/insulin aspart co-formulation (NN5401) in young adults and elderly T1DM patients (Europe); provided PK/PD basis for combination product development |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37863084 | 2023 | RCT | Lancet | ONWARDS 6 Phase 3a trial: once-weekly insulin icodec vs once-daily insulin degludec, both combined with insulin aspart, in T1DM adults; insulin aspart confirmed as standard bolus comparator in landmark T1DM trials |
| 36623517 | 2023 | RCT | Lancet Diabetes & Endocrinology | EXPECT trial (non-inferiority RCT): insulin degludec vs detemir combined with insulin aspart in pregnant T1DM women; confirmed safety and efficacy of insulin aspart as bolus insulin during T1DM pregnancy |
| 40129237 | 2025 | RCT | Diabetes, Obesity & Metabolism | Double-blind randomized crossover trial in T1DM adults using non-automated insulin pump + CGM: faster-acting insulin aspart vs insulin aspart; directly evaluated comparative efficacy and safety of both formulations |
| 21333580 | 2011 | Systematic Review | Diabetes & Metabolism | Systematic review comparing insulin aspart versus regular human insulin across T1DM and T2DM RCTs; demonstrated superior postprandial glucose control and comparable HbA1c with fewer hypoglycaemic episodes for insulin aspart |
| 12215068 | 2002 | Systematic Review | Drugs | Comprehensive early systematic review of insulin aspart in T1DM and T2DM; summarised multiple RCTs showing lower mean HbA1c, improved postprandial control, and reduced hypoglycaemia risk versus regular human insulin |
| 37290466 | 2023 | Guideline/Review | Lancet Diabetes & Endocrinology | Updated guideline on T1DM management in pregnancy; insulin aspart recommended as bolus insulin of choice; reviews integration of CGM and insulin pumps with insulin aspart for achieving glycaemic targets |
| 31902063 | 2020 | Review | Diabetes Therapy | Narrative review of insulin therapy strategies in adult T1DM; basal-bolus regimens with rapid-acting analogues including insulin aspart endorsed as standard of care; discusses CSII as preferred option for unmet targets |
| 15871555 | 2003 | Review | Treatments in Endocrinology | Spotlight review of insulin aspart in T1DM and T2DM; rapid absorption advantage over regular insulin confirmed; lower mean HbA1c and improved postprandial glucose across randomized trials |
| 25143741 | 2014 | Review | Vascular Health & Risk Management | Review of insulin degludec/insulin aspart co-formulation in T1DM and T2DM; mechanistic rationale for combining ultra-long basal insulin with rapid-acting insulin aspart for comprehensive daily glycaemic control |
| 18710361 | 2008 | Review | Expert Opinion on Pharmacotherapy | Evidence review of biphasic insulin aspart 30 in T1DM; evaluates premixed formulations as alternative to full basal-bolus regimens; supports formulation flexibility in T1DM insulin management |
Taiwan Market Information
Insulin aspart is currently not registered in Taiwan (TFDA market status: 未上市). There are no active marketing authorizations on record with the Taiwan Food and Drug Administration.
For reference: Insulin aspart is widely approved in all major global markets — as NovoRapid® (EU: EMA approval; Japan: PMDA approval) and NovoLog® (USA: FDA approval) — for the treatment of diabetes mellitus in adults, adolescents, and children. Taiwan registration may be pursued through a new drug application (NDA) referencing these existing international approvals.
Safety Considerations
Please refer to the SmPC for safety information.
TFDA package insert warnings and contraindications are not available in the current data package. These should be retrieved from the TFDA official website (download and parse the SmPC PDF) before proceeding to safety evaluation stage S1.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Insulin aspart is an established, globally-approved rapid-acting insulin analogue with abundant L1 evidence — including multiple completed Phase 3 RCTs — confirming its efficacy and safety in type 1 diabetes mellitus. The TxGNN prediction score of 99.95% is consistent with the mechanistic directness of this indication: T1DM requires absolute insulin replacement, and insulin aspart’s rapid-onset profile directly addresses the postprandial glucose dysregulation central to T1DM pathophysiology. The single constraint for Taiwan is the absence of TFDA registration.
To proceed, the following is needed:
- Regulatory: Submit new drug application (NDA) to TFDA for Type 1 Diabetes Mellitus indication, leveraging existing FDA/EMA approvals as reference
- Safety data gap (Blocking): Retrieve and parse the TFDA SmPC PDF to obtain Taiwan-specific warnings, contraindications, and precautionary labelling (DG001)
- MOA documentation (High): Query DrugBank API for complete mechanism of action data to support regulatory submission narrative (DG002)
- Drug interaction profile: Conduct full DDI search using alternative databases (the current query returned no results; cross-check with prescribing information)
- Taiwan pharmacovigilance: Prepare a post-marketing pharmacovigilance plan covering the Taiwan patient population, including any ethnic-specific dose titration considerations
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.