Identifying good responders to glucose lowering therapy in type 2 diabetes: implications for stratified medicine

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01503112.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Different methods of defining good responders to glucose lowering therapy identify different individuals.

Response definitions based on the top quartile of response for each method to give equal numbers of responders, n = 169.

Figure 2. Comparison of baseline HbA1c (a), diabetes duration (b) and C-peptide (c) in ‘responders’ and ‘non-responders’ to GLP-1A defined by HbA1c achieved or HbA1c change.

Responders n = 38, non responders n = 131.

Figure 3. Comparison of baseline HbA1c (a), diabetes duration (b) and C-peptide (c) in ‘responders’ and ‘non responders’ to GLP-1A defined by combined outcome or baseline adjusted HbA1c change (regression residuals).

Responders n = 38, non responders n = 131.