Identifying good responders to glucose lowering therapy in type 2 diabetes: implications for stratified medicine
Public Library of Science (PLoS)
2014 Jones et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
AIMS: Defining responders to glucose lowering therapy can be important for both clinical care and for the development of a stratified approach to diabetes management. Response is commonly defined by either HbA1c change after treatment or whether a target HbA1c is achieved. We aimed to determine the extent to which the individuals identified as responders and non-responders to glucose lowering therapy, and their characteristics, depend on the response definition chosen. METHODS: We prospectively studied 230 participants commencing GLP-1 agonist therapy. We assessed participant characteristics at baseline and repeated HbA1c after 3 months treatment. We defined responders (best quartile of response) based on HbA1c change or HbA1c achieved. We assessed the extent to which these methods identified the same individuals and how this affected the baseline characteristics associated with treatment response. RESULTS: Different definitions of response identified different participants. Only 39% of responders by one definition were also good responders by the other. Characteristics associated with good response depend on the response definition chosen: good response by HbA1c achieved was associated with low baseline HbA1c (p<0.001), high C-peptide (p<0.001) and shorter diabetes duration (p = 0.01) whereas response defined by HbA1c change was associated with high HbA1c (p<0.001) only. We describe a simple novel method of defining treatment response based on a combination of HbA1c change and HbA1c achieved that defines response groups with similar baseline glycaemia. CONCLUSIONS: The outcome of studies aiming to identify predictors of treatment response to glucose lowering therapy may depend on how response is defined. Alternative definitions of response should be considered which minimise influence of baseline glycaemia.
The PRIBA study was funded by the National Institute of Health Research (NIHR) (UK). AGJ is funded by an NIHR Doctoral Research Fellowship. ATH is an NIHR Senior Investigator and a Wellcome Trust Senior Investigator. ATH and BMS are core staff members of the NIHR Exeter Clinical Research Facility. WEH is partially supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula. The views given in this paper do not necessarily represent those of NIHR, the NHS or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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Vol. 9, e111235
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