Liraglutide
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Liraglutide
- Liraglutide: From Type 2 Diabetes Mellitus to Type 1 Diabetes Mellitus (Insulin-Adjunct Therapy)
Liraglutide: From Type 2 Diabetes Mellitus to Type 1 Diabetes Mellitus (Insulin-Adjunct Therapy)
Note on indication selection: This Evidence Pack contains 10 TxGNN-predicted indications for Liraglutide. Nine of them (opsismodysplasia, thiamine-responsive dysfunction syndrome, stiff person/stiff limb syndrome, autoimmune oophoritis, and four lipodystrophy variants) are rank-1–5 and rank-7–10 candidates scored purely on knowledge-graph proximity, carry zero clinical trial or literature support, and are explicitly flagged in their own rationale as lacking mechanistic basis (Evidence Level L5, decision stage S0, recommendation Hold). Only Type 1 Diabetes Mellitus (rank 6) is backed by substantive clinical and literature evidence. This report focuses on that candidate as the only one currently actionable for evaluation.
One-Sentence Summary
Liraglutide is a GLP-1 receptor agonist originally developed and marketed for Type 2 Diabetes Mellitus. The TxGNN model additionally predicts potential benefit as an adjunct-to-insulin therapy in Type 1 Diabetes Mellitus, and this direction is already supported by 50 clinical trials and 20 publications, including the completed Phase 3 ADJUNCT ONE/TWO program.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Type 2 Diabetes Mellitus (based on known drug class and trial descriptions; no Taiwan/EU license record found in this data pack — market status below) |
| Predicted New Indication | Type 1 Diabetes Mellitus (as adjunct to insulin) |
| TxGNN Prediction Score | 92.27% |
| Evidence Level | L1 |
| EU 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 in this Evidence Pack (MOA: [Data Gap]). Based on known pharmacology, liraglutide is a long-acting GLP-1 receptor agonist that glucose-dependently stimulates insulin secretion, suppresses glucagon secretion, and delays gastric emptying — mechanisms established through its approved use in Type 2 Diabetes Mellitus.
In Type 1 Diabetes Mellitus, pancreatic β-cells are largely destroyed by autoimmune attack and endogenous insulin secretion is minimal, but residual β-cell function and, more importantly, α-cell (glucagon) regulation may still respond to GLP-1 signaling. This provides a plausible rationale for liraglutide as an adjunct to insulin rather than a replacement — aiming to reduce insulin dose, improve glycemic variability, and support weight control, not to restore endogenous insulin production.
This mechanistic plausibility is corroborated by an unusually large and mature evidence base: the completed Phase 3 ADJUNCT ONE and ADJUNCT TWO trials (multinational, insulin-capped, placebo-controlled) directly tested this exact adjunct-therapy hypothesis in Type 1 Diabetes patients, along with multiple smaller Phase 3/4 trials and over a decade of published literature, including systematic reviews and meta-analyses.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02098395 | Phase 3 | Completed | 835 | ADJUNCT TWO — 26-week, insulin-capped, placebo-controlled, multinational trial evaluating liraglutide as adjunct to insulin in Type 1 Diabetes |
| NCT05467514 | Phase 3 | Completed | 35 | Liraglutide 1.8mg add-on to insulin for 6 months; effect on carotid intima-media thickness and cardiovascular risk factors in Type 1 Diabetes |
| NCT01612468 | Phase 4 | Completed | 100 | Randomized, double-blind, placebo-controlled study of liraglutide added to insulin on HbA1c, body weight, and hypoglycemia in poorly regulated Type 1 Diabetes |
| NCT02516657 | Phase 3 | Completed | 5 | Effect of liraglutide on glycemic control, glucagon secretion, and inflammatory markers in adolescents with Type 1 Diabetes |
| NCT02518945 | Phase 3 | Completed | 26 | Dapagliflozin as additional treatment to liraglutide and insulin in Type 1 Diabetes |
| NCT01592279 | Phase 4 | Unknown | 124 | GLP-1 analogue (incretin-based) treatment in uncontrolled Type 1 Diabetes patients |
| NCT06408532 | Phase 4 | Not yet recruiting | 256 | Switching to once-daily IDegLira (contains liraglutide) in patients on premixed insulin |
| NCT06387199 | Phase 2/3 | Recruiting | 26 | Weekly subcutaneous semaglutide (same class as liraglutide) reducing carbohydrate-counting burden in closed-loop insulin therapy for Type 1 Diabetes |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27506222 | 2016 | RCT | Diabetes Care | ADJUNCT ONE treat-to-target trial: liraglutide added to insulin improves glycemic control, reduces insulin requirement and body weight in Type 1 Diabetes |
| 33662334 | 2021 | RCT | Lancet Diabetes Endocrinol | Phase 2 trial of anti-IL-21 antibody plus liraglutide for preservation of β-cell function in recent-onset Type 1 Diabetes |
| 26926662 | 2016 | Review | Expert Opin Biol Ther | Reviews mechanism, efficacy, and safety of liraglutide as add-on to insulin in Type 1 Diabetes |
| 31203802 | 2020 | Review | Curr Diabetes Rev | Systematic review and meta-analysis of RCTs on liraglutide as adjunct to insulin in Type 1 Diabetes |
| 39192527 | 2024 | Cohort/RCT | Diabetes Obes Metab | NewLira study: liraglutide enhances insulin secretion and prolongs remission in newly diagnosed Type 1 Diabetes |
| 37561012 | 2023 | Review | J Clin Endocrinol Metab | Updated systematic review and meta-analysis of GLP-1 analogues as adjunctive therapy in Type 1 Diabetes |
| 31612934 | 2019 | Review | Am J Health Syst Pharm | Role of GLP-1 receptor agonists in Type 1 Diabetes treatment |
| 28304146 | 2017 | Cohort | Diabetes Obes Metab | Liraglutide acutely suppresses glucagon, lipolysis, and ketogenesis in Type 1 Diabetes |
| 34463425 | 2021 | Subgroup analysis | Diabetes Obes Metab | Efficacy and safety of liraglutide by baseline characteristics in ADJUNCT ONE/TWO trials |
| 39717993 | 2025 | Post hoc analysis | J Diabetes Sci Technol | Determinants of liraglutide treatment discontinuation, post hoc analysis of ADJUNCT ONE/TWO |
Safety Considerations
Please refer to the SmPC for safety information. Key warnings, contraindications, and drug-drug interaction data are not available in this Evidence Pack — TFDA label data collection is flagged as a Blocking data gap that must be resolved before any safety pre-assessment (S1) can proceed.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 RCTs (including the ADJUNCT ONE/TWO program) and a decade of consistent literature support liraglutide as adjunct-to-insulin therapy in Type 1 Diabetes, giving this candidate the highest evidence tier (L1) among all TxGNN predictions for this drug. However, this is an off-label adjunct use in a chronic autoimmune condition, and mandatory safety documentation is currently missing.
To proceed, the following is needed:
- TFDA-equivalent label warnings and contraindications (Blocking gap, DG001)
- Confirmed mechanism-of-action documentation from DrugBank (High priority gap, DG002)
- Drug-drug interaction profile (currently not_found)
- Confirmation of regulatory/marketing status, since current data shows “Not Marketed” with 0 authorizations
- Clarification of dosing/route requirements specific to the Type 1 Diabetes adjunct-therapy population (pediatric vs. adult, insulin-pump users, etc.)
The remaining 9 predicted indications in this pack (opsismodysplasia, thiamine-responsive dysfunction syndrome, stiff person/limb syndrome, autoimmune oophoritis, and the lipodystrophy variants) should remain at Hold — they have no clinical or literature evidence and no established mechanistic link, per their own rationale notes.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.