All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
All the issues raised by the reviewers have been satisfactorily addressed.
In their replies, the authors have satisfactorily addressed the major issues raised by this reviewer. The manuscript has been significantly improved and is now worth of publication. I do not have any further comments.
No comment
No comment
No comment
No comment
No comment
My concerns have been addressed, thus the paper is now susceptible for publication.
Both reviewers 1 and 2 raise issues on the experimental design, and especially on the choice of the HbA1c threshold for patients' categorisation.
[# PeerJ Staff Note: Please ensure that all review comments are addressed in a rebuttal letter and any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate. It is a common mistake to address reviewer questions in the rebuttal letter but not in the revised manuscript. If a reviewer raised a question then your readers will probably have the same question so you should ensure that the manuscript can stand alone without the rebuttal letter. Directions on how to prepare a rebuttal letter can be found at: https://peerj.com/benefits/academic-rebuttal-letters/ #]
In this well-written, retrospective cohort study, Sia and colleagues investigated the clinical predictors of first-year treatment failure in 5579 Asian patients newly diagnosed with type 2 diabetes mellitus (T2DM). As demonstrated in the UKPDS trial, achieving early glycemic control can significantly reduce the long-term risk of microvascular and macrovascular complications in newly diagnosed T2DM patients, however, many uncertainties and controversies surround the possible predictors of poor glycemic responses in real life scenarios and further evidences are required in this field. Despite its interesting subject matter, unfortunately, the present investigation has major methodological flaws that would inflate the validity of the findings and predictive modeling.
1. The study participants were enrolled across a very long-time window (Jan 2002-Dec 2017, 16 years), thus implying that available first-line pharmacological treatment options (e.g. metformin, insulin secretagogues, DPP4 inhibitors, SGLT2 inhibitors, acarbose, TZDs, GLP1RAs, insulin) varied considerably, depending on whether these newly diagnosed T2DM patients initiated treatment earlier or later in the study window. Other than a different glycemic efficacy, the occurrence of first-year treatment failure may reflect either a specific medication intolerance, that often prevents patients maintaining their therapy, or therapeutic inertia, which is a non-negligible problem among diabetes care providers. Failing to control for these confounding variables, and their combined effects, may have distorted the associations, and should be regarded as an important study limitation.
2. Beside pharmacological treatment options, also glycemic targets have varied considerably during this wide study window, so that the definition of treatment failure used (“never achieving post-treatment HbA1c <8% at 3, 6, 9, or 12 months after initiating treatment during the first year”, lines 94-95) appears misleading. It is true that before 2004, the American Diabetes Association (ADA) recommended that HbA1c not be allowed to exceed 8.0%. However, since 2004, the ADA dropped the traditional 8.0% “action threshold” in favor of a general recommendation to treat most patients to <7.0%, especially those newly diagnosed with T2DM and expected to get clinical advantage of metabolic legacy. Few exceptions to this general recommendation are represented by frail, older adults (> 65 years of age), in which less stringent HbA1c targets are recommended (8-8.5%) since late 2000s. I would suggest narrowing the study window to ensure more homogeneous criteria for treatment and outcomes of the study participants, redefining treatment failure, and excluding elderly patients with high Charlson comorbidity index scores from the primary analysis.
3. Although legitimate, backward stepwise regression modeling is particularly subjected to multicollinearity problems when the predictive variables are intercorrelated. The methods section should explain how multicollinearity was handled.
See the points above.
No comment
No comment
No comment
This paper focuses on an interesting topic. However, there is a major concern that must be addressed.
The authors stated that “Participants with at least one of the four post-treatment HbA1c levels <8% were categorized as non-TF (reference group)”. This critical choice must be strongly supported, otherwise it appears arbitrary and invalidates the study conclusions. Why didn’t they choose only the HbA1c value at the end of the observation? In my opinion this value is more appropriate as cut-off between TF and non-TF. In any case, please, show in table the HbA1c values at the four assessments.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.