Manuscript ID: DOM-19-0849-RA
Journal: Diabetes, Obesity and Metabolism
Title: Effectiveness of herbal medicines for weight loss: a systematic review and meta-analysis of randomised controlled trials

This systematic review and meta-analysis evaluated the efficacy and safety of herbal medicines for treating excess weight in healthy adults with overweight or obesity. The authors have included a total of 54 randomised placebo-controlled trials, and concluded that the current clinical evidence from randomised placebo-controlled trials is not sufficient enough for recommending these herbal medicines for reducing excess body weight in healthy adults with overweight or obesity.

The authors of this study before its publication require considering the following changes in the manuscript.

 The authors, in eligibility criteria, mentioned that “only randomised placebo-controlled trials (RCTs) were eligible for inclusion” however, it is not clear whether the authors included RCTs of parallel-group or cross-over or both.

 The risk of bias tool (reference 30) which was used in this study seems to be for parallel-group RCT, but no clear details are reported by the authors.

 Authors need to justify the use of random effects models in the meta-analysis.

 Authors, in Garcinia cambogia and Phaseolus vulgaris, mentioned that “one study each was excluded from the meta-analysis due to incomplete data (reference 53 and 59);” did authors check the availability of clinical study report (CSR) or searched the trial if available in the clinical trial registry like CT.gov.

 Irvingia gabonensis: Authors mentioned that “as only three studies were identified, a meta-analysis could not be conducted.” However, in general, at least two (or more than two) studies are required for conducting meta-analysis, though the complete requirement depends on the power of the statistical tests in meta-analysis.

 In Herb medicine preparations with one RCT only, authors reported that “seventeen studies used herbal medicines that were utilised in only one RCT each,” however, for example, authors did not include another placebo-controlled RCT in Zingiber officinale which reported the outcome weight loss. Considering this, the authors need to rework on the search strategy and also screening of studies for inclusion.

Reference: Ebrahimzadeh Attari V, Asghari Jafarabadi M, Zemestani M, Ostadrahimi A. Effect of Zingiber officinale supplementation on obesity management with respect to the uncoupling protein 1‐3826A> G and ß3‐adrenergic receptor Trp64Arg polymorphism. Phytotherapy Research. 2015 Jul;29(7):1032-9 (https://www.ncbi.nlm.nih.gov/pubmed/25899896).

 Authors are requested to provide the statements (judgment) for risk of bias for all 54 included studies as supplementary document.

 The study concluded that the current clinical evidence from 54 RCTs is not sufficient enough to recommend the herbal medicines (listed in the systematic review) for reducing the body weight in healthy adults with overweight or obesity. However, this conclusion should be read with caution as 44% of the included studies asked the participants to maintain their usual dietary intake, the participants from 43% of the studies provided with dietary advice or meal plans for general health and/or weight loss, or were provided with a normo-caloric diet through food deliveries (4 studies).

The remaining studies provided participants with low-calorie, meal replacement shakes. In terms of physical activity, 70% of studies requested participants to maintain their usual levels, 20% of studies provided advice for exercise, and 9% of studies held exercise sessions for participants to attend.

As exercise and diet are contributing factors for weight loss in addition to supplementation of herbal medicines, based on this heterogeneity of included placebo-controlled RCTs, the conclusion of the study should be more robust rather than stating a general conclusion for the overall of body of evidence.

The authors have addressed most of the reviewers' comments with relevant responses in the revised submission.

However, the authors did not respond to the query where it was suggested to rework on the search strategy and also screening of studies for inclusion in order to not miss any relevant study which meets inclusion criteria.

The mention of Ebrahimzadeh Attari 2015 (41) study is an example which the authors missed to include (in the previous submission), but not the complete list of studies.

The authors have to double-check the literature hits, if required, to make sure that they did not miss any relevant study for inclusion.

The authors have addressed and responded to all the queries from reviewers and can be considered for publication in its current form.