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 is a rapid-acting insulin analogue already used for glycaemic control in diabetes mellitus. The TxGNN model predicts it may be effective for Type 1 Diabetes Mellitus, supported by 75+ clinical trials and 20 publications — but this indication substantially overlaps with the drug's existing, well-established clinical use rather than representing a novel repurposing opportunity.

Quick Overview

Item	Content
Original Indication	Diabetes mellitus (glycaemic control) — detailed approved indication text not on file (data gap)
Predicted New Indication	Type 1 Diabetes Mellitus
TxGNN Prediction Score	99.55%
Evidence Level	L1
Germany Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available (data gap). Based on known pharmacology, insulin glulisine is a recombinant rapid-acting human insulin analogue that binds the insulin receptor to lower blood glucose, and it is already used clinically for mealtime (bolus) glycaemic control in both type 1 and type 2 diabetes.

Because type 1 diabetes mellitus is characterised by absolute insulin deficiency, insulin replacement — including rapid-acting analogues like glulisine — is the established standard of care rather than a new therapeutic hypothesis. The evidence pack itself flags this explicitly: the mechanistic link here is "the drug's own original indication rather than a repurposing inference," meaning the TxGNN prediction largely recovers existing, well-documented clinical knowledge instead of surfacing a novel use.

It is also worth noting that among the ten TxGNN predictions supplied in this evidence pack, only rank 1 (Type 1 Diabetes Mellitus) is backed by direct trial/literature evidence (L1). Ranks 2–10 (e.g., thiamine-responsive dysfunction syndrome, opsismodysplasia, stiff person syndrome, lipodystrophy variants) all scored L4–L5 with no supporting trials or literature, and several appear to reflect knowledge-graph artefacts — including at least two cases where the "predicted indication" is actually a known adverse effect of insulin injection (localized lipodystrophy/lipoatrophy) rather than a treatable target, i.e., a possible reversed-causality signal. These should not be advanced without independent mechanistic review.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT07070752	Phase 3	Completed	224	Non-inferior immunogenicity, efficacy and safety of biosimilar GP40321 vs Apidra® in T1DM
NCT01194258	Phase 2	Completed	132	Double-blind crossover comparing rHuPH20-formulated prandial insulins to insulin lispro
NCT02509429	Phase 2	Completed	24	Closed-loop artificial pancreas reduces nocturnal hypoglycaemia in children with T1DM
NCT00546702	Phase 3	Completed	142	26-week efficacy/safety of insulin glulisine + glargine in T1DM (HbA1c, hypoglycaemia)
NCT00467376	Phase 3	Completed	485	Glulisine vs lispro (with glargine) in T1/T2DM: efficacy, safety, hypoglycaemia frequency
NCT01159353	Phase 1	Completed	37	PK/PD comparison of glulisine vs aspart post-prandial glucose control
NCT02871089	N/A	Active, not recruiting	96	Closed-loop insulin delivery from T1D onset; residual beta-cell function
NCT02914886	Phase 4	Completed	14	Zinc-free insulin (glulisine) effect on lipoatrophy in T1D pump users
NCT03495908	N/A	Completed	136	Regular vs rapid-acting insulin via V-Go wearable delivery device
NCT02814123	Phase 2	Completed	28	Closed-loop fast-acting insulin ± pramlintide co-administration in T1DM

Literature Evidence

PMID	Year	Type	Journal	Key Findings
16308840	2005	RCT	Horm Metab Res	Multinational RCT comparing efficacy/safety of glulisine vs lispro in adults with T1DM
41366610	2026	RCT (Phase III)	Diabetes Obes Metab	Biosimilar insulin glulisine (T-Glu) non-inferior to originator (R-Glu) in T1DM
21457066	2011	RCT	Diabetes Technol Ther	3-way crossover: glulisine vs aspart vs lispro via CSII pump in T1DM
21291333	2011	RCT	Diabetes Technol Ther	26-week trial: comparable efficacy/safety of glulisine vs lispro in pediatric T1DM
19614947	2009	RCT	Diabetes Obes Metab	Glulisine vs lispro efficacy/safety in Japanese patients with T1DM
35933650	2022	Cohort/Comparative	Acta Diabetol	Real-world comparison of glulisine vs lispro/aspart for CSII in T1DM
28544684	2017	Cohort	Pediatr Int	Glulisine for CSII in pediatric T1DM: 1-year efficacy/safety data
16123473	2005	PK Study	Diabetes Care	Pharmacokinetics and prandial glucose control of glulisine in children/adolescents with T1DM
19496630	2009	Review	Drugs	Overview of insulin glulisine's role in diabetes management
35650058	2022	Case report	Nihon Ronen Igakkai Zasshi	Switching degludec→glulisine improved nocturnal hypoglycaemia/arrhythmia in elderly T1DM patient

Germany Market Information

Currently not marketed in Germany — no marketing authorizations are on file for this candidate (0 licenses recorded).

Safety Considerations

Please refer to the package insert for safety information. (TFDA warnings/contraindications and DDI data are currently unavailable — flagged as a blocking data gap, DG001.)

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Evidence is strong (L1: multiple completed Phase 2/3 RCTs, including a 2026 Phase III biosimilar trial) for insulin glulisine's efficacy and safety in type 1 diabetes mellitus. However, this is confirmatory evidence for an already-known use rather than a novel repurposing signal, and two blocking/high-severity data gaps (TFDA labeling, MOA documentation) remain unresolved before any safety-relevant decision can be finalized.

To proceed, the following is needed:

TFDA package insert warnings and contraindications (DG001, blocking — required before S1 safety review)
Detailed mechanism of action documentation from DrugBank (DG002)
Clarification of regulatory/commercial status given zero current marketing authorizations
Reassessment of whether rank-1 "prediction" should be reclassified as label-confirmation rather than repurposing, and independent review of ranks 2–10 (all L4/L5, including two likely reversed-causality signals) before any further action
Disclaimer

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