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Study · Case report or series · n = 4 · 2021

7 results

Case Report: Off-Label Liraglutide Use in Children With Wolfram Syndrome Type 1: Extensive Characterization of Four Patients.

Frontino G, Raouf T, Canarutto D, Tirelli E, Di Tonno R, Rigamonti A, Cascavilla ML, Baldoli C, Scotti R, Leocani L, Huang SC, Meschi F and 7 more

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Barera G, Broccoli V, Rossi G, Torchio S, Chimienti R, Bonfanti R, Piemonti L

Frontiers in pediatrics14 Dec 2021Cited by 27 (Europe PMC)

PMID34970515 (opens in a new tab)PMCIDPMC8712700 (opens in a new tab)DOI10.3389/fped.2021.755365 (opens in a new tab)PepBankPUB-34970515
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Summary

Aims: Wolfram syndrome type 1 is a rare recessive monogenic form of insulin-dependent diabetes mellitus with progressive neurodegeneration, poor prognosis, and no cure. Based on preclinical evidence we hypothesized that liraglutide, a glucagon-like peptide-1 receptor agonist, may be repurposed for the off-label treatment of Wolfram Syndrome type 1. We initiated an off-label treatment to investigate the safety, tolerability, and efficacy of liraglutide in pediatric patients with Wolfram Syndrome type 1. Methods: Pediatric patients with genetically confirmed Wolfram Syndrome type 1 were offered off-label treatment approved by The Regional Network Coordination Center for Rare Diseases, Pharmacological Research IRCCS Mario Negri, and the internal ethics committee. Four patients were enrolled; none refused nor were excluded or lost during follow-up. Liraglutide was administered as a daily subcutaneous injection. Starting dose was 0.3 mg/day. The dose was progressively increased as tolerated, up to the maximum dose of 1.8 mg/day. The primary outcome was evaluating the safety, tolerability, and efficacy of liraglutide in Wolfram Syndrome type 1 patients. Secondary endpoints were stabilization or improvement of C-peptide secretion as assessed by the mixed meal tolerance test. Exploratory endpoints were stabilization of neurological and neuro-ophthalmological degeneration, assessed by optical coherence tomography, electroretinogram, visual evoked potentials, and magnetic resonance imaging. Results: Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months. Liraglutide was well-tolerated: all patients reached and maintained the maximum dose, and none withdrew from the study. Only minor transient gastrointestinal symptoms were reported. No alterations in pancreatic enzymes, calcitonin, or thyroid hormones were observed. At the latest follow-up, the C-peptide area under the curve ranged from 81 to 171% of baseline. Time in range improved in two patients. Neuro-ophthalmological and neurophysiological disease parameters remained stable at the latest follow-up. Conclusions: We report preliminary data on the safety, tolerability, and efficacy of liraglutide in four pediatric patients with Wolfram Syndrome type 1. The apparent benefits both in terms of residual C-peptide secretion and neuro-ophthalmological disease progression warrant further studies on the repurposing of glucagon-like peptide-1 receptor agonists as disease-modifying agents for Wolfram Syndrome type 1.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

  1. 01HumanCase report or seriesSafety outcome

    In four children with Wolfram syndrome type 1, all patients reached and maintained the maximum liraglutide dose.

    In plain wordsIn four children with Wolfram syndrome, all reached and kept the highest liraglutide dose.

    Peptide
    Liraglutide
    Outcome
    Not applicableTolerability and maximum dose reached
    Study

    n = 4

    Analysis
    Primary
    Outcome group
    Adverse events · Whole body
    Studied dose
    0.3 mg/day start, increased up to 1.8 mg/day · subcutaneous · 8-27 monthsAs given in this study (human).

    Source sentences

    Summary
    Liraglutide was well-tolerated: all patients reached and maintained the maximum dose
    1 context sentence
    Summary · context
    Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months.
  2. 02HumanCase report or seriesSafety outcome

    In four children with Wolfram syndrome type 1, no patient withdrew from liraglutide treatment.

    In plain wordsIn four children with Wolfram syndrome, nobody stopped liraglutide treatment.

    Peptide
    Liraglutide
    Outcome
    No significant changeWithdrawals
    Study

    n = 4

    Analysis
    Primary
    Outcome group
    Adverse events · Whole body
    Studied dose
    0.3 mg/day start, increased up to 1.8 mg/day · subcutaneous · 8-27 monthsAs given in this study (human).

    Source sentences

    Summary
    none withdrew from the study.
    1 context sentence
    Summary · context
    Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months.
  3. 03HumanCase report or seriesSafety outcome

    In four children with Wolfram syndrome type 1, only minor transient gastrointestinal symptoms were reported with liraglutide.

    In plain wordsIn four children with Wolfram syndrome, liraglutide caused only minor, short-lived stomach and gut symptoms.

    Peptide
    Liraglutide
    Outcome
    Not applicableGastrointestinal symptoms
    Study

    n = 4

    Analysis
    Primary
    Outcome group
    Gastrointestinal adverse events · Gastrointestinal
    Studied dose
    0.3 mg/day start, increased up to 1.8 mg/day · subcutaneous · 8-27 monthsAs given in this study (human).

    Source sentences

    Summary
    Only minor transient gastrointestinal symptoms were reported.
    1 context sentence
    Summary · context
    Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months.
  4. 04HumanCase report or seriesSafety outcome

    In four children with Wolfram syndrome type 1, no alterations in pancreatic enzymes, calcitonin or thyroid hormones were observed during liraglutide treatment.

    In plain wordsIn four children with Wolfram syndrome, liraglutide did not change pancreatic enzymes, calcitonin or thyroid hormones.

    Peptide
    Liraglutide
    Outcome
    No significant changePancreatic enzymes, calcitonin and thyroid hormones
    Study

    n = 4

    Analysis
    Primary
    Outcome group
    Adverse events · Endocrine and hormones
    Studied dose
    0.3 mg/day start, increased up to 1.8 mg/day · subcutaneous · 8-27 monthsAs given in this study (human).

    Source sentences

    Summary
    No alterations in pancreatic enzymes, calcitonin, or thyroid hormones were observed.
    1 context sentence
    Summary · context
    Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months.
  5. 05HumanCase report or seriesEfficacy outcome

    In four children with Wolfram syndrome type 1, the C-peptide area under the curve at latest follow-up ranged from 81 to 171% of baseline during liraglutide treatment.

    In plain wordsIn four children with Wolfram syndrome, C-peptide response ranged from 81 to 171% of baseline on liraglutide.

    Peptide
    Liraglutide
    Outcome
    MixedC-peptide area under the curve at latest follow-up
    Study

    n = 4

    Analysis
    Secondary
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    0.3 mg/day start, increased up to 1.8 mg/day · subcutaneous · 8-27 monthsAs given in this study (human).

    Measurements

    C-peptide AUC
    81 to 171 % of baseline
    latest follow-up

    Source sentences

    Summary
    At the latest follow-up, the C-peptide area under the curve ranged from 81 to 171% of baseline.
    1 context sentence
    Summary · context
    Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months.
  6. 06HumanCase report or seriesEfficacy outcome

    In four children with Wolfram syndrome type 1, neuro-ophthalmological and neurophysiological disease parameters remained stable at the latest follow-up during liraglutide treatment.

    In plain wordsIn four children with Wolfram syndrome, eye and nerve measures stayed stable on liraglutide.

    Peptide
    Liraglutide
    Outcome
    No significant changeNeuro-ophthalmological and neurophysiological disease parameters
    Study

    n = 4

    Analysis
    Exploratory
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    0.3 mg/day start, increased up to 1.8 mg/day · subcutaneous · 8-27 monthsAs given in this study (human).

    Source sentences

    Summary
    Neuro-ophthalmological and neurophysiological disease parameters remained stable at the latest follow-up.
    1 context sentence
    Summary · context
    Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months.
  7. 07HumanCase report or seriesEfficacy outcome

    In four children with Wolfram syndrome type 1, time in range improved in two patients during liraglutide treatment.

    In plain wordsIn four children with Wolfram syndrome, time in range improved in two patients on liraglutide.

    Peptide
    Liraglutide
    Outcome
    IncreaseTime in range
    Study

    n = 4

    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    0.3 mg/day start, increased up to 1.8 mg/day · subcutaneous · 8-27 monthsAs given in this study (human).

    Source sentences

    Summary
    Time in range improved in two patients.
    1 context sentence
    Summary · context
    Four patients aged between 10 and 14 years at baseline were treated with liraglutide for 8-27 months.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    12 Oct 2026, 11:11 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:05 UTC

    First added · source update from Europe PMC

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