The article by Seidu et al addresses a relevant clinical question in current clinical practice.

The main objective was to evaluate the efficacy and safety of initial combination therapy vs. the stepwise approach in subjects with a recent diagnosis of type 2 diabetes.

Therefore, they performed a systematic review of the literature including randomized controlled trials and observational studies. They used state-of-the-art methodology, with no major issues affecting its validity.

This reviewer is hereby kindly requesting that the authors address the following issues:

• Please, explain the reason for not including other databases (e.g., EMBASE) in their literature search. Please, discuss this as a potential limitation of the paper.

• It is not clear whether they adopted language restrictions in their literature search. Please, explain under Methods.

• From the information included the reader understands that the literature search only yielded 27 references. Please, confirm this explicitly.

• Under Outcomes, please, explain what is the definition of "adverse events".

• After reviewing the studies included to evaluate the effect of combination therapy on hypoglycemia, it is pretty clear the comparison arm (stepwise approach) included antidiabetic therapies associated with increased risk of hypo, while the combination therapy arms did not.

Here, the authors cannot conclude that the initial combination therapy reduced the risk of hypoglycemia as the intrinsic risk by therapy allocation was on the comparison arm. Please, make changes and discuss this accordingly.

• In the discussion and the conclusions (also in the Abstract), it should be clear to the reader that there is a lack of sufficient evidence to recommend initial combination therapy, at least for relevant clinical outcomes.

The authors have addressed all the comments made by this reviewer