University of Oulu

Kero, J., Koskenniemi, J. J., Karsikas, S., Pokka, T., Lou, O., Toppari, J., & Veijola, R. (2022). innovative trial design for testing the efficacy, safety and tolerability of 6‐month treatment with incretin‐based therapy to prevent type 1 diabetes in autoantibody positive participants: A protocol for three parallel double‐blind, randomised controlled trials(investdia). Diabetic Medicine, 39(10).

INnoVative trial design for testing the Efficacy, Safety and Tolerability of 6-month treatment with incretin-based therapy to prevent type 1 DIAbetes in autoantibody positive participants : a protocol for three parallel double-blind, randomised controlled trials (INVESTDIA)

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Author: Kero, Jukka1,2,3; Koskenniemi, Jaakko J.1,2,3; Karsikas, Sara2;
Organizations: 1Research Centre for Integrative Physiology and Pharmacology, Institute of Biomedicine, University of Turku, Turku, Finland
2Department of Paediatrics, Turku University Hospital, Turku, Finland
3Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
4Department for Children and Adolescents, Oulu University Hospital, Oulu, Finland
5Department of Paediatrics, PEDEGO Research Unit, MRC Oulu, University of Oulu, Oulu, Finland
6JDRF, New York, New York, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.2 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2022-12-28


Aims: β-cell stress and dysfunction may contribute to islet autoimmunity and progression to clinical type 1 diabetes. We present a protocol of three randomised controlled trials assessing the effects of glucagon-like peptide 1 (GLP − 1) analogue liraglutide in three early stages of type 1 diabetes.

Methods: We will test 10- to 30-year-old people with multiple islet autoantibodies for their glucose metabolism and randomise participants with stage 1 (multiple islet autoantibodies and normoglycaemia), stage 2 (multiple islet autoantibodies and dysglycaemia) and early stage 3 (clinical diagnosis) type 1 diabetes, 10−14 persons in each, to a 6-month intervention with liraglutide or placebo with 6-month follow-up in the stage 2 and stage 3 trials and 18-month follow-up in the stage 1 trial. Primary efficacy outcome in the stage 1 and stage 2 trials is a first-phase insulin response in an intravenous glucose tolerance test and C-peptide area under the curve in a 2-h mixed-meal tolerance test in the stage 3 trial. In addition, safety and tolerability of liraglutide treatment will be assessed.

Conclusions: Most prevention trials of type 1 diabetes have targeted the immune system. Treatment with GLP-1 analogue liraglutide supports the pancreatic β-cells, which should likewise attenuate islet autoimmunity. Our innovative study design allows simultaneous investigation of an intervention in three groups of people who represent various early stages of type 1 diabetes and maximises the eligibility to participate.

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Series: Diabetic medicine
ISSN: 0742-3071
ISSN-E: 1464-5491
ISSN-L: 0742-3071
Volume: 39
Issue: 10
Article number: e14913
DOI: 10.1111/dme.14913
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
317 Pharmacy
Funding: These are investigator-initiated clinical trials. The work is supported by JDRF International, a non-profit foundation for type 1 diabetes research (grant numbers 3-SRA-2014-301-M-R, 3-SRA-2016-142-M-R and 3-SRA-2016-143-M-R). JDRF also follows the progress of the study. Study drug and placebo are donated by Novo Nordisk for the stage 1 trial. The design, management, analysis and reporting of the study are entirely independent of Novo Nordisk. Neither JDRF nor Novo Nordisk have any role in the data interpretation and reporting.
Copyright information: © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.