Non-Alcoholic Fatty Liver Disease (NAFLD) is a highly prevalent disease and unmet clinical need that we have recently proposed to be renamed for simplicity and accuracy as Fatty Liver Disease (FLD), with specific subclassifications. It has been commonly associated with metabolic comorbidities, including obesity, type 2 diabetes (T2D), hypertension, and hyperlipidemia. Since no Federal and Drug Administration (FDA) approved treatments exist to date, recent guidelines recommend lifestyle interventions, bariatric surgery, and pharmacotherapy, i.e. glucagon-like peptide-1 receptor agonists (GLP-1RA), peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, and SGLT-2 inhibitors for its treatment. A new and novel medication for the treatment of T2D, tirzepatide, a dual GIP/GLP-1RA, was approved by the FDA only one week after guidelines were published, and ongoing clinical trials demonstrate promising results not only for T2D but also for body weight and steatosis. Moreover, we realize that distinct subgroups exist under the umbrella of FLD and, thus, more precise therapeutic recommendations would be needed towards the goal of personalized medicine and therapeutics for these subgroups. As the metabolism field is moving forward very fast and as several molecules in development will most likely demonstrate benefits in NAFLD treatment in the foreseeable future, guidelines will need to be frequently updated. This rapid pace of change prompts us to propose that guidelines should exist as living online documents on the websites of professional societies, so that they continue being updated following and reflecting the rapid progress in this and other fields of medicine.

In June 2020, the Taskforce of the Guideline Workshop 2019 convened via teleconferencing to initiate a pilot project that demonstrates the various processes and considerations involved in developing high-quality, evidence-based clinical practice guidelines for the medical management of individuals with type 2 diabetes (T2D) and its associated comorbidities, including cardiovascular disease (CVD) and chronic kidney disease (CKD). The goal of the pilot project was to create evidence-based guidelines for use of sodium-glucose transport protein 2 inhibitors (SGLT2-I) when managing very high risk T2D patients, evidenced by the presence of both CVD and CKD. For this purpose the Taskforce represented a guideline panel and made use of synthesized evidence from an ongoing BMJ Rapid Recommendations project on SGLT2-I and GLP-1 receptor agonists. Results from the Taskforce pilot project demonstrated the value, feasibility and utility of using a step-wise approach to identifying and grading evidence and then developing actionable recommendations for utilizing SGLT2-I in this at-risk T2D population. This report describes the various steps involved in the process and explains how it can be utilized to rapidly develop recommendations in a format that is easy to use and can be quickly updated as new evidence becomes available, also within the emerging concept of living guidelines.