Insulin Glulisine

證據等級: L5

預測適應症: 10 個

Insulin Glulisine: From Diabetes Mellitus to Type 1 Diabetes Mellitus

One-Sentence Summary

Insulin glulisine (Apidra) is a rapid-acting human insulin analogue approved globally for prandial glycaemic control in patients with diabetes mellitus; it is not currently registered in Singapore. The TxGNN model predicts it may be effective for Type 1 Diabetes Mellitus (T1DM) — importantly, this constitutes a validation prediction that confirms the drug's primary established indication worldwide rather than identifying a genuinely novel repurposing opportunity. With 50 clinical trials and 19 publications identified, the evidence base is exceptionally robust at Evidence Level L1.

Quick Overview

Item	Content
Original Indication	Not registered in Singapore; globally approved for diabetes mellitus (prandial glycaemic control)
Predicted New Indication	Type 1 Diabetes Mellitus
TxGNN Prediction Score	99.55%
Evidence Level	L1
Singapore Market Status	✗ Not Marketed
Number of Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from this evidence pack's structured fields. Based on well-established pharmacological knowledge, insulin glulisine is a rapid-acting human insulin analogue (brand name: Apidra, Sanofi). It incorporates two amino acid substitutions in the B chain — asparagine at position B3 is replaced by lysine, and lysine at position B29 is replaced by glutamic acid — which reduces insulin self-association and accelerates subcutaneous absorption compared to regular human insulin, producing an onset of action within approximately 15 minutes and a duration of approximately 4 hours.

Type 1 Diabetes Mellitus is characterised by autoimmune destruction of pancreatic β-cells, resulting in absolute insulin deficiency. External insulin replacement is the cornerstone of T1DM management. Insulin glulisine's rapid onset and short duration of action precisely mimic physiological prandial insulin secretion, making it biologically ideal for managing postprandial glycaemic excursions in T1DM patients across all age groups, including paediatric populations.

A critical contextual note: TxGNN's top-ranked prediction for insulin glulisine is T1DM — its primary globally approved indication. This TxGNN result represents model validation rather than drug repurposing. The practical implication for Singapore is that a well-evidenced, internationally established therapy currently lacks local registration, representing a potential access gap for T1DM patients who require rapid-acting prandial insulin coverage.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00964574	Phase 4	Completed	68	Multicentre study directly evaluating efficacy and safety of insulin glulisine in T1DM patients also using insulin glargine as basal; assessed HbA1c change, insulin dosing, and patient satisfaction
NCT03328845	Phase 4	Completed	300	Compared the influence of different rapid-acting insulin analogues (including glulisine) on oxidative stress parameters in T1DM patients; high relevance, large sample, completed
NCT01204593	Phase 4	Completed	206	Multinational non-comparative study of glargine once-daily + glulisine three times-daily in T1DM patients previously uncontrolled on any insulin regimen; primary endpoint HbA1c change at week 24
NCT00546702	Phase 3	Completed	142	Multicentre, non-randomised Phase 3 evaluating efficacy (HbA1c change) and safety of insulin glulisine in T1DM over 26 weeks; insulin glargine used as basal component
NCT00046150	Phase 3	Completed	59	Multinational randomised controlled trial comparing safety of insulin glulisine vs insulin aspart in continuous subcutaneous insulin infusion (CSII) in T1DM; assessed catheter occlusions, HbA1c, and hypoglycaemia rates
NCT00467376	Phase 3	Completed	485	Randomised, parallel-group study comparing efficacy and safety of insulin glulisine to insulin lispro in T1DM and T2DM patients using insulin glargine as basal; 12-week HbA1c primary endpoint
NCT04974528	Phase 3	Completed	319	Open-label randomised trial comparing inhaled insulin Afrezza vs rapid-acting insulin analogues (including glulisine) combined with basal insulin in paediatric T1DM and T2DM over 26 weeks
NCT00174668	Phase 3	Completed	311	Multinational open randomised trial demonstrating superior efficacy of an intensified insulin glulisine + glargine regimen over a conventional two-injection regimen in poorly controlled diabetes
NCT02518945	Phase 3	Completed	26	Randomised double-blind placebo-controlled study of dapagliflozin as adjunct to liraglutide and insulin (including rapid-acting) in T1DM; examined glycaemic control, variability reduction, and weight outcomes
NCT04124302	Phase 4	Completed	76	Compared two insulin dose calculation approaches on postprandial glycaemia after mixed meals in children with T1DM; relevant to rapid-acting insulin optimisation in paediatric T1DM

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35933650	2022	Comparative RCT	Acta Diabetologica	Described T1DM population using glulisine vs lispro/aspart for CSII therapy; evaluated relative effectiveness on HbA1c, fasting glucose, dose requirements, and rates of hypoglycaemia and diabetic ketoacidosis
16308840	2005	RCT	Hormone and Metabolic Research	Multinational, multicentre, randomised, parallel-group trial (n=683) comparing glulisine to lispro in adult T1DM; demonstrated comparable glycaemic efficacy and a similar safety profile
28544684	2017	Clinical Study	Pediatrics International	Evaluated efficacy and safety of insulin glulisine for CSII in 20 children with T1DM over 1 year; showed significant improvement in postprandial glucose after breakfast and dinner, with no increase in hypoglycaemic events
19496630	2009	Systematic Review	Drugs	Comprehensive systematic review of insulin glulisine for glycaemic management in adults, adolescents, and children; concluded it is effective and broadly comparable to other rapid-acting analogues with a favourable tolerability profile
18076215	2008	PK/PD Study	Clinical Pharmacokinetics	Detailed pharmacokinetic and pharmacodynamic characterisation of insulin glulisine; documented faster absorption, earlier peak, and shorter duration of action compared to regular human insulin
19216625	2009	Review	Expert Opinion on Biological Therapy	Reviewed optimisation of basal/bolus therapy using insulin glulisine; discussed its role in physiologically mirroring prandial insulin secretion and implications for early insulin initiation strategies
23243636	2012	Review	Drugs of Today	Reviewed rapid-acting insulin analogues (including glulisine) in T1DM children and adolescents; compared pharmacokinetic profiles, clinical outcomes, and approval status across paediatric age groups
17703632	2007	Review	Vascular Health and Risk Management	Reviewed strategies for combining insulins including glulisine for optimal glycaemic control in T1DM and T2DM; discussed pharmacokinetic limitations of conventional insulins and the advantages of rapid-acting analogues
16193096	2005	Drug Review	Drugs of Today	Early drug profile of insulin glulisine; characterised its rapid-action pharmacokinetic profile, pre- and post-meal dosing flexibility, and potential advantages over conventional insulin therapy in clinical diabetes management
35650058	2022	Case Report	Japanese Journal of Geriatrics	Case of an 82-year-old T1DM patient with chronic heart failure: switching from insulin degludec to glulisine improved nocturnal hypoglycaemia and ventricular arrhythmia; illustrates the importance of insulin selection in complex comorbid T1DM

Singapore Market Information

Insulin glulisine is currently not registered in Singapore. There are no active or historical product licences on record with the Health Sciences Authority (HSA).

Globally, insulin glulisine is marketed under the brand name Apidra (Sanofi-Aventis) and holds regulatory approvals from major agencies, including:

US FDA (approved 2004) — for improvement of glycaemic control in adults with T1DM and T2DM
European Medicines Agency (EMA) — approved for adults, adolescents, and children ≥6 years with T1DM or T2DM
Health Canada and multiple other national regulators

There is no Singapore-equivalent product licence to tabulate at this time.

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: This TxGNN result validates insulin glulisine's primary globally approved indication (T1DM) at Evidence Level L1, supported by multiple completed Phase 3 and Phase 4 randomised trials; however, the drug is entirely absent from the Singapore market, creating a potential access gap for T1DM patients who require rapid-acting prandial insulin analogues.

To proceed, the following is needed:

Initiate or verify an HSA registration pathway for Singapore; assess whether a reference product dossier (US FDA/EMA approval) can be leveraged for expedited review
Obtain and review the full prescribing information (package insert) to document official warnings, contraindications, and drug-drug interactions for local labelling
Confirm cold-chain supply logistics, storage infrastructure, and distributor agreements for insulin products in Singapore
Review the Ministry of Health (MOH) Singapore clinical practice guidelines for T1DM to confirm that insulin glulisine aligns with current national standards of care
Develop a pharmacovigilance and post-market safety monitoring plan, with particular attention to hypoglycaemia risk in local patient populations
Explore health technology assessment (HTA) requirements, including cost-effectiveness data relative to alternative rapid-acting insulins already registered in Singapore (e.g., insulin aspart, insulin lispro)
Disclaimer

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