Insulin Glulisine
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Insulin Glulisine: Thiamine-responsive dysfunction syndrome
One-Sentence Summary
Insulin glulisine is a rapid-acting human insulin analogue, originally used to treat diabetes mellitus and diabetic ketoacidosis. The TxGNN model predicts it may be effective for thiamine-responsive dysfunction syndrome, with 30 clinical trials and 20 publications compiled for this report. Note that type 1 diabetes is already an established use of this drug, so this is confirmation of an existing indication rather than true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Thiamine-responsive dysfunction syndrome |
| TxGNN Prediction Score | 0.9947 |
| Evidence Level | L5 (see note below) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Evidence level note: The trial records compiled for this report include several Phase 3 studies, such as NCT00115570, NCT00290979, NCT00467376 and NCT04974528, all completed. At least two completed Phase 3 trials supports L1. Most of the Phase 3 studies are open-label and are comparisons against insulin lispro or aspart, or against premixed insulin.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on established knowledge, insulin glulisine is a rapid-acting human insulin analogue. It binds the insulin receptor, promoting peripheral glucose uptake and suppressing hepatic glucose output. Its onset is faster and its duration shorter than regular human insulin.
Type 1 diabetes is characterised by absolute insulin deficiency, so mealtime insulin replacement is a core treatment. The original indication of diabetes mellitus already covers this condition, which explains the very high model score. The prediction is mechanistically coherent, but it does not represent a new therapeutic use.
Clinical Trial Evidence
The compiled data contain 30 registered trials. The 10 most relevant are listed below (all completed). No ANZCTR identifiers were found in the data.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00115570 | Phase 3 | Completed | 572 | Glulisine vs lispro in children and adolescents with type 1 diabetes; 26-week safety and efficacy comparison |
| NCT00290979 | Phase 3 | Completed | 250 | Glulisine vs lispro in type 1 diabetes; 28-week non-inferiority study of HbA1c change |
| NCT00467376 | Phase 3 | Completed | 485 | Glulisine vs lispro with glargine in type 1 or 2 diabetes; efficacy, safety and hypoglycaemia frequency |
| NCT07070752 | Phase 3 | Completed | 224 | Immunogenicity of biosimilar GP40321 vs Apidra SoloStar in type 1 diabetes |
| NCT00135941 | Phase 3 | Completed | 582 | Glargine plus glulisine multiple daily injections vs premix insulin; patient-reported outcomes |
| NCT01194245 | Phase 2 | Completed | 135 | Randomised double-blind crossover study of prandial insulins (lispro-PH20 or aspart-PH20) vs lispro in type 1 diabetes |
| NCT01621776 | N/A | Completed | 107 | Glulisine vs lispro for post-prandial hyperglycaemia in a real-world setting |
| NCT00607087 | Phase 4 | Completed | 289 | Glulisine vs aspart and lispro in pump therapy; unexplained hyperglycaemia and infusion set occlusion |
| NCT00384085 | Phase 4 | Completed | 588 | Glargine with stepwise glulisine vs twice-daily premixed insulin in type 2 diabetes; 64 weeks |
| NCT01204593 | Phase 4 | Completed | 206 | Glargine plus glulisine basal-bolus therapy in uncontrolled type 1 diabetes; HbA1c change over 24 weeks |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16308840 | 2005 | RCT | Horm Metab Res | Glulisine vs lispro in adults with type 1 diabetes (683 randomised); open-label, multinational efficacy and safety comparison |
| 19614947 | 2009 | RCT | Diabetes Obes Metab | Glulisine vs lispro with glargine in Japanese patients with type 1 diabetes |
| 20150026 | 2010 | Systematic Review | Endocr Pract | Rapid-acting analogues vs regular human insulin in basal-bolus regimens for type 1 diabetes |
| 23243636 | 2012 | Systematic Review | Drugs Today | Insulin analogues for type 1 diabetes in children and adolescents |
| 35933650 | 2022 | Comparative Study | Acta Diabetol | Glulisine vs lispro and aspart in pump treatment of type 1 diabetes; HbA1c, dose, and hypoglycaemia and ketoacidosis rates |
| 19496630 | 2009 | Review | Drugs | Glulisine in diabetes management; similar glucose effects to lispro, faster onset than regular human insulin |
| 16706558 | 2006 | Review | Drugs | Glulisine glycaemic control similar to regular human insulin in type 1 diabetes |
| 28544684 | 2017 | Clinical study | Pediatr Int | Glulisine by CSII in 20 children with type 1 diabetes; post-meal glucose improved over 1 year |
| 18076215 | 2008 | Pharmacology review | Clin Pharmacokinet | Pharmacokinetics and pharmacodynamics: faster absorption and shorter duration than regular insulin |
| 25865292 | 2016 | Review | Diabetes Metab Res Rev | Continuous subcutaneous insulin infusion; glulisine among the rapid-acting analogues of choice |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 12268Q | Apidra SoloStar | Injection (human analogue), cartridges, 100 units per mL, 3 mL, 5 | Not listed in the data compiled for this report |
Safety Considerations
- Drug Interactions: The interaction query returned 100 records. Most of those displayed are Moderate. Main examples include:
- Glucose-raising or glycaemic-effect agents: phenylephrine, pseudoephedrine, epinephrine, salbutamol, formoterol, hydrocortisone, ethinylestradiol, estradiol, hydrochlorothiazide, acetazolamide
- Other glucose-lowering agents (additive hypoglycaemia risk): metformin, pioglitazone, alogliptin, albiglutide
- Beta-blocker acebutolol (may mask hypoglycaemia symptoms)
- Alcohol (ethanol), doxycycline and alpelisib
- Minor: topical hydrocortisone and topical alclometasone
For warnings and contraindications, please refer to the TGA-approved Product Information (PI) for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Type 1 diabetes is an established use of insulin glulisine, supported by several completed Phase 3 trials and RCTs against other rapid-acting insulins. The other nine predicted indications (for example thiamine-responsive dysfunction syndrome, opsismodysplasia and the stiff person disorders) have no trials or literature and rest on model association only. Several, such as the localised lipodystrophies, may reflect insulin’s known injection-site adverse effects. Pancreatic agenesis is mechanistically coherent for insulin replacement but is unsupported by data here.
To proceed, the following is needed:
- Confirm the approved indication text for Apidra SoloStar in the ARTG, which is blank in the compiled data
- Obtain the TGA Product Information to complete the warnings and contraindications review
- Obtain detailed mechanism of action data
- Review the interacting drugs, particularly other glucose-lowering agents and beta-blockers, in a local prescribing guardrail
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.