Insulin Glulisine
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Insulin Glulisine: From Diabetes Mellitus to Type 1 Diabetes Mellitus
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 type 1 diabetes mellitus, with 30 clinical trials and 20 publications currently supporting this direction. Note that type 1 diabetes is already a core marketed use of this drug, so this is a label-concordant indication rather than true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Diabetes mellitus; diabetic ketoacidosis (the Singapore licence text is blank, so these come from the knowledge-graph indication data) |
| Predicted New Indication | Type 1 diabetes mellitus |
| TxGNN Prediction Score | 99.55% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Insulin glulisine is a rapid-acting human insulin analogue. It binds the insulin receptor and lowers blood glucose by promoting peripheral glucose uptake and suppressing hepatic glucose production. It is used as mealtime insulin within basal-bolus or insulin-pump regimens. Detailed mechanism-of-action data were not available in the data compiled for this report, so this description relies on general pharmacological knowledge.
Type 1 diabetes is a disease of absolute insulin deficiency, and mealtime insulin replacement is the standard of care. The original indication (diabetes mellitus) already covers this condition. The high TxGNN score therefore reflects a well-established use rather than a new discovery.
On grading: the trial list contains Phase 2 and Phase 4 trials and several Phase 3 studies. Many of the Phase 3 trials have not been individually appraised for relevance. The level was assigned conservatively as L2 from the data supplied. Pivotal trials such as PMID 16308840 and 19614947 appear in the literature list, and a fuller review could justify a higher level.
Clinical Trial Evidence
The data include 30 registered trials. The 10 most relevant are listed below, favouring those with the strongest relevance grades and the largest enrollment.
| Trial Number | Phase | Status | Enrollment | 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 (HMR1964) vs lispro in type 1 diabetes; 28-week non-inferiority on HbA1c |
| NCT00467376 | Phase 3 | Completed | 485 | Glulisine vs lispro with glargine in type 1 or 2 diabetes; 12 weeks, efficacy and hypoglycaemia frequency |
| NCT00046150 | Phase 3 | Completed | 59 | Glulisine vs aspart in insulin pumps (CSII); catheter occlusion and safety |
| NCT00397553 | Phase 3 | Completed | 104 | Non-randomised local study of glulisine with glargine in type 1 diabetes |
| NCT01848990 | Phase 4 | Completed | 456 | CONSISTENT 1: hyaluronidase pre-treatment in CSII, HbA1c and safety (grade A) |
| NCT00384085 | Phase 4 | Completed | 588 | Glargine plus stepwise glulisine vs premixed insulin in type 2 diabetes, 64 weeks (grade A) |
| NCT01194245 | Phase 2 | Completed | 135 | Randomised double-blind crossover of prandial insulins with PH20 in type 1 diabetes (grade A) |
| NCT00607087 | Phase 4 | Completed | 289 | Glulisine vs aspart and lispro in pumps; unexplained hyperglycaemia and infusion-set occlusion |
| NCT01621776 | N/A | Completed | 107 | Glulisine vs lispro for post-meal hyperglycaemia in real-world use (grade B) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16308840 | 2005 | RCT | Horm Metab Res | Multinational open-label study (683 randomised adults) comparing glulisine with lispro in type 1 diabetes |
| 19614947 | 2009 | RCT | Diabetes Obes Metab | Glulisine vs lispro with glargine in Japanese patients with type 1 diabetes |
| 23243636 | 2012 | Systematic Review | Drugs Today | Insulin analogues, including glulisine, 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: HbA1c, hypoglycaemia, dose |
| 35933650 | 2022 | Comparative Study | Acta Diabetol | Glulisine vs lispro and aspart in pump treatment: HbA1c, fasting glucose, hypoglycaemia and DKA rates |
| 19496630 | 2009 | Review | Drugs | Glulisine has a faster onset than regular human insulin; effects on glucose are similar to lispro |
| 16706558 | 2006 | Review | Drugs | Glycaemic control similar to regular human insulin in type 1 diabetes after 12 weeks |
| 28544684 | 2017 | Clinical study | Pediatr Int | One-year pump use in 20 children; post-meal glucose improved after breakfast and dinner |
| 18076215 | 2008 | Pharmacology review | Clin Pharmacokinet | Faster absorption, earlier onset and shorter duration than regular human insulin |
| 25865292 | 2016 | Review | Diabetes Metab Res Rev | Populations, safety, efficacy and economics of continuous subcutaneous insulin infusion |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13432P | Apidra SoloStar 100 Units/ml Solution for injection in a pre-filled pen | Injection, solution | Not stated in the registration data |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 interacting drugs; 20 were reviewed here. Most are of moderate severity, and a few are minor. Main examples:
- Other glucose-lowering agents (metformin, pioglitazone, alogliptin, albiglutide): additive blood-glucose-lowering effects.
- Beta-agonists and sympathomimetics (salbutamol, formoterol, epinephrine, phenylephrine, pseudoephedrine): may blunt glucose control.
- Corticosteroids (hydrocortisone, with topical forms rated minor), estrogens (estradiol, ethinylestradiol), and thiazides (hydrochlorothiazide): may raise glucose levels.
- Beta-blocker (acebutolol), acetazolamide, doxycycline, alpelisib, and ethanol: moderate-level interactions that can alter glucose response or mask hypoglycaemia.
- Standard insulin precautions: Monitor for hypoglycaemia, injection-site lipodystrophy, and dose titration needs. In pump use, watch for pump failure.
Warnings and contraindications from the package insert were not available in the data compiled for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Type 1 diabetes is a core use of insulin glulisine, backed by many completed Phase 2 to Phase 4 trials and published RCTs, systematic reviews and pump studies. The drug is already marketed in Singapore. The main gaps are in labelling and safety documentation, not in evidence of efficacy.
To proceed, the following is needed:
- The package insert from the Health Sciences Authority (HSA) with warnings and contraindications, which is a blocking gap for safety screening
- The approved indication text for SIN13432P, which is blank in the registration data
- Detailed mechanism-of-action data from DrugBank
- A formal review of the Phase 3 trials, to confirm whether the evidence level can be raised above L2
- A safety monitoring plan covering hypoglycaemia, injection-site reactions, and pump-related risks
Other predictions (all Hold): The other nine predicted indications have no trials or literature (evidence level L5) and should not proceed. Examples are thiamine-responsive dysfunction syndrome, stiff person syndrome and pancreatic agenesis. Several likely reflect comorbidity artifacts. The lipodystrophy-related predictions probably reflect adverse effects of injected insulin rather than a treatment benefit.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.