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Introduction: Innovation through the repurposing of generic drugs encloses several advantages when compared with the process of developing new drugs from scratch. Metformin is an established and inexpensive antidiabetic drug for which anticancer properties have been hypothesised. A systematic review of observational studies found promising results for metformin related to breast cancer in women with diabetes. Although the number of randomised clinical trials of metformin for the treatment of breast cancer increased over the last decades, the overall landscape of those studies in this heterogeneous field remains unclear. Hence, we designed the present scoping review protocol to map the literature on randomised clinical trials of metformin in the treatment of breast cancer to determine the value and scope of future systematic reviews on this subject and identify research gaps., Methods: We will search MEDLINE (via PubMed), EMBASE, CENTRAL, LILACS, Web of Science and sources of grey literature. We will include any randomised clinical trial of metformin for the treatment of breast cancer in adult women, and will not impose restrictions regarding context, language or publication date. Two independent reviewers will screen and select studies, and chart the data. We will structure the presentation of our results based on the molecular types of breast cancer, their stages and treatment modalities., Ethics and Dissemination: As a literature review, this study is exempt from ethics approval. Findings will be disseminated through presentations in conferences and a peer-reviewed publication. OPEN SCIENCE FRAMEWORK REGISTRATION: osf.io/yquba., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Frailty has been defined as a clinical syndrome of multicausal origin characterized by a reduction of physiologic reserves that increase the vulnerability of an individual to adverse outcomes such as the development of functional dependence and death. Considered one of the most important geriatric syndromes, frailty's prevention and management represent important goals for gerontology and geriatrics. Although nutrition plays an important role within the multifactorial susceptibility for this syndrome, up to the present no systematic review specifically addressed the effectiveness of nutritional interventions for the treatment of frailty. Therefore, we propose the present systematic review with the aim to assess the effectiveness of nutritional interventions for the treatment of frailty in older adults living in the community or in long-term care facilities., Methods: We will search Medline (via Pubmed), Embase, Cinahl, Central, Lilacs, Web of Science, and sources of gray literature. We will accept trials whereby the unit of randomization consisted of individuals or clusters of individuals. Our primary outcome is all-cause mortality. Secondary outcomes are quality of life, functional status, cognitive function, frailty status, body composition, and physical activity. Risk of bias will be assessed using the Cochrane Collaboration tool. We will analyze the overall strength of the evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Two independent researchers will conduct all evaluations and any disagreements will be resolved through the participation of a 3rd author. If possible, we will perform random-effects meta-analyses and subgroup analyses concerning specific details of nutritional interventions (e.g., components and duration), research scenario, risk of bias, and criteria used to diagnose frailty., Conclusion: In this systematic review protocol we outline the details of the aims and methods of a systematic review on the effectiveness of nutritional interventions for the management of frailty in older adults living in the community or in long-term care facilities". We believe this wording to be more objective and balanced than the previous one. We understand that it is not ideal to propose changes to the text after manuscripts have been accepted. However, we feel that the new wording of the conclusion section of the abstract is more consistent with the overall content of the main text of the review than its previous version. Hence, we hope you may accept our request.