Insulin Detemir
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Insulin Detemir: From Diabetes Mellitus to Type 1 Diabetes Mellitus
One-Sentence Summary
Insulin detemir is a long-acting basal insulin analogue, originally used to treat diabetes mellitus and diabetic ketoacidosis. The TxGNN model predicts it may be effective for type 1 diabetes mellitus, which is in fact already part of its established, marketed use rather than a true new indication. The data compiled for this report include 39 clinical trials and 20 publications that support this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Diabetes mellitus; diabetic ketoacidosis (the Singapore licence records contain no indication text) |
| Predicted New Indication | Type 1 diabetes mellitus |
| TxGNN Prediction Score | 99.77% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, insulin detemir is a soluble, long-acting human insulin analogue. It binds to the insulin receptor and replaces deficient endogenous insulin. A fatty acid (myristic acid) modification allows it to bind reversibly to albumin, which gives slow absorption and an effect lasting up to 24 hours. The published reviews in the evidence set describe this profile.
Type 1 diabetes is a form of diabetes mellitus, the drug's original indication, and it is defined by absolute insulin deficiency. This makes it the classic setting for basal insulin replacement. The prediction is therefore reasonable, but it largely confirms existing on-label use rather than identifying a new therapeutic opportunity.
Other predictions (ranks 2–10) have no clinical trials or literature and are model output only. Examples include autoimmune oophoritis, opsismodysplasia and stiff person syndrome. Several likely reflect comorbidity or adverse-effect associations in the knowledge graph (for example, lipodystrophy is a known injection-site effect of insulin). Pancreatic agenesis is biologically plausible because insulin replacement is the standard treatment for the resulting diabetes, but it has no supporting studies here. None of these is recommended for advancement at this stage.
Clinical Trial Evidence
The data include 39 trials for type 1 diabetes. The 10 most relevant are listed below, prioritising those graded most relevant and then larger completed studies.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00595374 | Phase 3 | Completed | 114 | Detemir + aspart vs NPH + aspart in adults with type 1 diabetes; efficacy and safety on blood glucose control |
| NCT00447382 | Phase 3 | Completed | 330 | 12-month double-blind comparison of detemir from the current vs the NN729 production process, with aspart as bolus insulin |
| NCT00312156 | Phase 3 | Completed | 347 | Detemir vs NPH (each with aspart) in children and adolescents with type 1 diabetes |
| NCT00184639 | Phase 3 | Completed | 71 | 32-week comparison of detemir and insulin semilente MC in patients aged 6–21 years |
| NCT00978627 | Phase 3 | Completed | 548 | IDegAsp once daily vs detemir + aspart basal-bolus in type 1 diabetes (detemir as comparator) |
| NCT01835431 | Phase 3 | Completed | 362 | IDegAsp vs detemir (each with aspart) in children and adolescents (detemir as comparator) |
| NCT00117780 | Phase 4 | Completed | 520 | Detemir once vs twice daily in a basal-bolus regimen with aspart; HbA1c and hypoglycaemia |
| NCT01542463 | N/A | Completed | 4,464 | Non-interventional study of safety, glycaemic control and weight in type 1 or type 2 diabetes |
| NCT00322257 | Phase 3 | Terminated | 596 | Inhaled vs injected mealtime insulin, both with detemir as basal insulin (indirect relevance) |
| NCT01440439 | Phase 4 | Unknown | 30 | Detemir vs glargine and glycaemic control during exercise |
Most of the remaining trials are observational safety and effectiveness studies from Europe, Asia, Africa and North America, along with small pharmacokinetic and pharmacodynamic studies. Several Phase 3 trials use detemir as a comparator or background insulin, so they support its use but do not test it as the primary intervention.
Literature Evidence
The 10 most relevant of the 20 publications are listed below, with randomised trials and systematic reviews prioritised.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36623517 | 2023 | RCT | Lancet Diabetes Endocrinol | EXPECT: degludec vs detemir (both with aspart) in pregnant women with type 1 diabetes; non-inferiority trial |
| 33662147 | 2021 | Systematic review | Cochrane Database Syst Rev | (Ultra-)long-acting insulin analogues in type 1 diabetes, with a focus on complications and hypoglycaemia |
| 29477399 | 2018 | Network meta-analysis | Value Health | Relative efficacy and safety of basal insulin regimens in adults with type 1 diabetes |
| 21878861 | 2011 | Meta-analysis | Pol Arch Med Wewn | Detemir vs NPH insulin in type 1 diabetes |
| 36763996 | 2022 | Meta-analysis | Clin Ther | Efficacy and tolerability of degludec vs other long-acting analogues, including detemir |
| 23243636 | 2012 | Systematic review | Drugs Today | Insulin analogues, including detemir, for children and adolescents with type 1 diabetes |
| 17326333 | 2006 | Review | Vasc Health Risk Manag | Detemir has a less variable pharmacokinetic profile than NPH or ultralente and may reduce hypoglycaemia risk |
| 15516157 | 2004 | Review | Drugs | Detemir has a more predictable, consistent effect than NPH insulin, with up to 24 hours of action |
| 20539842 | 2010 | Review | Vasc Health Risk Manag | Update on detemir as a basal analogue with a lower rate of hypoglycaemia |
| 17881328 | 2007 | Review | Endocrinol Metab Clin North Am | Pharmacology of detemir: B30 threonine removal and myristic acid acylation enabling albumin binding |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13115P | LEVEMIR® FLEXPEN® 100U/ML, 3ML | Injection, solution | Not recorded in the licence data |
| SIN15515P | LEVEMIR® PENFILL® 100 U/ML | Injection, solution | Not recorded in the licence data |
Both licences are valid single-ingredient products from Novo Nordisk, and none has been cancelled.
Safety Considerations
- Drug Interactions: The interaction screening returned 100 interacting drugs, and 20 were provided for review. Most are rated Moderate and a few are Minor. Examples are listed below.
- Other glucose-lowering agents: metformin, pioglitazone, alogliptin and albiglutide
- Sympathomimetics and bronchodilators: epinephrine, phenylephrine, pseudoephedrine, salbutamol and formoterol
- Beta-blockers: acebutolol
- Corticosteroids: hydrocortisone
- Others: ethinylestradiol, estradiol, hydrochlorothiazide, acetazolamide, doxycycline, alpelisib and ethanol
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 trials and several systematic reviews support insulin detemir in type 1 diabetes, and two licences are valid in Singapore. This is an established use, not a new indication. Any further work should be framed as confirming and positioning existing use. The other predicted indications (ranks 2–10) have no supporting evidence and should remain on Hold, except pancreatic agenesis, which is best treated as a research question.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA, which are currently missing
- Mechanism of action data (for example from DrugBank)
- The approved indication wording for the two Singapore licences
- Confirmation that the Singapore labelled indication explicitly covers type 1 diabetes
- For any rare-disease use such as pancreatic agenesis, a case series or other supporting clinical data
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.