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 insulin analogue, originally used to treat diabetes mellitus and diabetic ketoacidosis. This is effectively an on-label use rather than true repurposing, so the prediction is best read as a confirmation of the drug’s established role.
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 |
| Canada Market Status | Marketed (marketed DINs: 3 of 3) |
| Number of DINs | 3 (marketed: 3) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known information, insulin glulisine is a rapid-acting human insulin analogue that activates the insulin receptor to lower blood glucose. Its efficacy in diabetes mellitus has been established.
Type 1 diabetes is characterised by absolute insulin deficiency, so mealtime insulin replacement is mechanistically well suited. Insulin glulisine is already a core therapy for diabetes mellitus, which means the type 1 diabetes prediction is concordant with the known pharmacology and is an on-label use rather than a new repurposing direction.
Several of the other lower-ranked predictions (for example classic stiff person syndrome and autoimmune oophoritis) most likely reflect comorbid diabetes rather than a disease-modifying effect. Scores for predictions such as drug-induced localized lipodystrophy and pressure-induced localized lipoatrophy come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence, because injection-site lipodystrophy is a known adverse effect of insulin. None of these has any supporting clinical evidence.
Clinical Trial Evidence
The data compiled for this report include 30 registered trials. The 10 most relevant are listed below, favouring larger, randomised, directly comparative studies.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00115570 | Phase 3 | Completed | 572 | Glulisine vs lispro in children and adolescents with type 1 diabetes (26 weeks) |
| NCT00290979 | Phase 3 | Completed | 250 | Non-inferiority of glulisine vs lispro on HbA1c change in type 1 diabetes (28 weeks) |
| NCT00467376 | Phase 3 | Completed | 485 | Glulisine vs lispro with glargine in type 1 or 2 diabetes (12 weeks) |
| NCT00046150 | Phase 3 | Completed | 59 | Safety of glulisine vs insulin aspart in insulin pumps (CSII) in type 1 diabetes |
| NCT00397553 | Phase 3 | Completed | 104 | Open-label efficacy and safety of glulisine with glargine in type 1 diabetes |
| NCT01194245 | Phase 2 | Completed | 135 | Randomised crossover of prandial insulins with hyaluronidase (PH20) vs insulin lispro in type 1 diabetes |
| NCT00607087 | Phase 4 | Completed | 289 | Glulisine vs aspart and lispro in insulin pumps: hyperglycaemia and infusion set occlusion |
| NCT01848990 | Phase 4 | Completed | 456 | CONSISTENT 1: hyaluronidase pre-treatment of the infusion site in type 1 diabetes on CSII; HbA1c over 6 months |
| NCT00384085 | Phase 4 | Completed | 588 | Glargine with stepwise glulisine vs premixed insulin in type 2 diabetes (64 weeks) |
| NCT01204593 | Phase 4 | Completed | 206 | Basal-bolus glargine plus glulisine in uncontrolled type 1 diabetes; HbA1c change over 24 weeks |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16308840 | 2005 | RCT | Horm Metab Res | Multinational open-label comparison of glulisine vs lispro in adults with type 1 diabetes (683 randomised) |
| 19614947 | 2009 | RCT | Diabetes Obes Metab | Glulisine vs lispro with glargine in Japanese patients with type 1 diabetes |
| 35933650 | 2022 | RCT | Acta Diabetol | Glulisine vs lispro and aspart in pump treatment of type 1 diabetes: HbA1c, dose, and hyper-/hypoglycaemia and DKA rates |
| 23243636 | 2012 | Systematic Review | Drugs Today | Insulin analogues for type 1 diabetes in children and adolescents |
| 20150026 | 2010 | Systematic Review | Endocr Pract | Rapid-acting analogues vs regular human insulin in basal-bolus regimens in type 1 diabetes |
| 19496630 | 2009 | Review | Drugs | Review of glulisine in diabetes: effective vs other short- and rapid-acting insulins |
| 16706558 | 2006 | Review | Drugs | Faster onset and shorter duration than regular human insulin, with similar glycaemic control |
| 17703632 | 2007 | Review | Vasc Health Risk Manag | Combining insulins for optimal glucose control, with a focus on glulisine |
| 28544684 | 2017 | Clinical study | Pediatr Int | Glulisine in CSII in 20 children with type 1 diabetes: post-meal glucose improved after 1 year |
| 18076215 | 2008 | Pharmacology review | Clin Pharmacokinet | Pharmacokinetics and pharmacodynamics: faster absorption and shorter duration than regular insulin |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02279479 | APIDRA | Not specified | Not specified |
| 02294346 | APIDRA | Not specified | Not specified |
| 02279460 | APIDRA | Not specified | Not specified |
Safety Considerations
- Drug Interactions: 100 interactions were identified in the interaction database. Most of those reviewed are of moderate severity, and a few are minor. Examples include:
- Beta-agonists and sympathomimetics (salbutamol, formoterol, epinephrine, phenylephrine, pseudoephedrine)
- Other antidiabetic agents (metformin, pioglitazone, alogliptin, albiglutide)
- Corticosteroids (hydrocortisone)
- Beta-blockers (acebutolol)
- Thiazide and carbonic anhydrase inhibitor diuretics (hydrochlorothiazide, acetazolamide)
- Ethinylestradiol and estradiol, alpelisib, doxycycline and ethanol
- Injection-site lipodystrophy is a recognised adverse effect of insulin injections (see the lipodystrophy predictions above).
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 3 trials and randomised studies, along with systematic reviews, support insulin glulisine in type 1 diabetes, and the drug is already marketed in Canada. Because this is an established on-label use, the main limits are the missing package insert safety data and the lack of mechanism data, rather than a lack of efficacy evidence. Evidence is classified as L2 under the stated rules, although the number of completed Phase 3 studies suggests it may be stronger than this.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications (a blocking gap for the safety screening step)
- Detailed mechanism of action data
- Approved indication text and dosage form for the three Canadian DINs
- A review of the moderate-severity interactions, particularly with other glucose-lowering agents, beta-blockers and corticosteroids, to define monitoring guardrails
- The other nine predicted indications (rank 2–10) should stay on Hold. Pancreatic agenesis is the only one with a plausible rationale (insulin replacement), and would need dedicated neonatal safety and dosing evaluation.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.