Insulin Glulisine
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Insulin Glulisine
- Insulin Glulisine: From Diabetes Mellitus Glycaemic Control to Type 1 Diabetes Mellitus
Insulin Glulisine: From Diabetes Mellitus Glycaemic Control to Type 1 Diabetes Mellitus
One-Sentence Summary
Insulin glulisine (Apidra) is a rapid-acting human insulin analogue used at mealtimes to improve glycaemic control in diabetes mellitus. The TxGNN model predicts it for type 1 diabetes mellitus (T1DM), and this is effectively its established labelled use rather than a true repurposing. Evidence retrieved includes 50 registered clinical trials (many in type 2 diabetes or otherwise off-target) and 19 publications, including several randomised T1DM trials.
Quick Overview
| Item | Content |
|---|---|
| Predicted New Indication | Type 1 diabetes mellitus |
| TxGNN Prediction Score | 99.55% |
| Evidence Level | L1 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 1 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the Evidence Pack. Based on known pharmacology, insulin glulisine is a rapid-acting human insulin analogue that binds the insulin receptor and lowers blood glucose. In T1DM it replaces the missing mealtime (prandial) insulin.
The SAHPRA record supplied lists no approved indication text, and no original indication was captured in the pack. The published literature describes glulisine as approved for improving glycaemic control in adults, adolescents and children with diabetes mellitus. The T1DM prediction therefore reflects the drug’s existing use. The high TxGNN score is consistent with this, but it should not be read as a new-indication signal.
The other nine predicted indications (ranks 2 to 10) have no trials or literature in the pack. Most look like knowledge-graph artefacts:
- Comorbidity links: stiff person syndrome, autoimmune oophoritis.
- Insulin as the cause: injection-site lipodystrophy and lipoatrophy.
- Most biologically coherent: pancreatic agenesis, where insulin replacement is standard care for neonatal insulin-deficient diabetes. A targeted literature search would be a reasonable next step.
Clinical Trial Evidence
Trials were selected from titles and summaries for T1DM relevance. The pack does not confirm the population of every trial, so verify against the registry record before citing. No SANCTR or PACTR identifiers were present in the pack.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00290979 | Phase 3 | Completed | 250 | Randomised non-inferiority study of glulisine vs insulin lispro in T1DM over 28 weeks (HbA1c change, safety) |
| NCT00546702 | Phase 3 | Completed | 142 | Non-randomised 26-week study of glulisine with glargine in T1DM (HbA1c, safety) |
| NCT00046150 | Phase 3 | Completed | 59 | Randomised 12-week safety comparison of glulisine vs insulin aspart in pumps (CSII) in T1DM, including catheter occlusions |
| NCT00271284 | Phase 3 | Completed | 88 | Randomised crossover of glargine vs detemir, both with glulisine boluses, in T1DM (fasting glucose variability) |
| NCT00467376 | Phase 3 | Completed | 485 | 12-week randomised comparison of glulisine vs lispro in T1DM or T2DM, all on glargine |
| NCT01202474 | Phase 4 | Completed | 100 | Apidra plus Lantus basal-bolus in children and adolescents with T1DM (proportion reaching HbA1c targets) |
| NCT00964574 | Phase 4 | Completed | 68 | Open, non-randomised study of glulisine efficacy and safety in T1DM patients also on glargine |
| NCT00489190 | Phase 4 | Completed | 45 | Local 12-week study collecting effectiveness and safety data for Apidra in T1DM |
| NCT00913497 | Phase 4 | Completed | 16 | Crossover of glulisine vs aspart on breakfast postprandial glucose in prepubertal children with T1DM |
| NCT01678235 | Phase 4 | Completed | 64 | Double-blind crossover of glulisine vs aspart after a high-glycaemic-index meal in children on pumps |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16308840 | 2005 | RCT | Horm Metab Res | Multinational open-label randomised comparison of glulisine vs lispro in adults with T1DM (683 randomised); efficacy and safety endpoints |
| 21457066 | 2011 | RCT | Diabetes Technol Ther | Three-way crossover of glulisine vs aspart vs lispro in pump therapy in T1DM |
| 21291333 | 2011 | Trial (26-week) | Diabetes Technol Ther | Glulisine vs lispro in a basal-bolus regimen in paediatric T1DM; comparable efficacy and safety |
| 19614947 | 2009 | Comparative study | Diabetes Obes Metab | Glulisine vs lispro in Japanese T1DM patients using glargine as basal insulin |
| 23243636 | 2012 | Systematic review | Drugs Today | Insulin analogues, including glulisine, in children and adolescents with T1DM |
| 16123473 | 2005 | PK/PD clinical trial | Diabetes Care | Pharmacokinetics, postprandial glucose control and safety of glulisine vs regular human insulin in paediatric T1DM |
| 35933650 | 2022 | Cohort | Acta Diabetol | Glulisine vs lispro and aspart in T1DM pump patients: HbA1c, fasting glucose, dose, hypoglycaemia and DKA rates |
| 28544684 | 2017 | Cohort | Pediatr Int | Twenty children on CSII: post-breakfast and post-dinner glucose improved significantly after one year of glulisine |
| 19496630 | 2009 | Review | Drugs | Faster onset than regular insulin, similar glucose effects to lispro, effective vs other rapid-acting insulins |
| 18076215 | 2008 | Review | Clin Pharmacokinet | Pharmacokinetics and pharmacodynamics: faster absorption, earlier onset and shorter duration than regular human insulin |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. A38/21.1/0506 | Apidra | Injection | Not stated in the registration record supplied |
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: At least two completed Phase 3 randomised trials in T1DM support glulisine (NCT00290979, NCT00271284), backed by randomised literature (PMID 16308840) and paediatric data. This meets L1, but it confirms an established use rather than a new indication. Proceeding is conditional on safety review, because the SAHPRA PI has not yet been obtained.
To proceed, the following is needed:
- Download and review the SAHPRA package insert for warnings, contraindications and the approved indication text (a blocking gap for safety screening).
- Verify the T1DM vs T2DM population of each cited trial against its registry record.
- Retrieve DrugBank mechanism-of-action data.
- If the aim is genuine repurposing, run a targeted search on neonatal diabetes and pancreatic agenesis. The other low-ranked predictions should stay on hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.