Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes Mellitus (T2DM) are increasing rapidly worldwide, reaching epidemic proportions. Their association, based on common metabolic risk factors (obesity, insulin resistance (IR), unhealthy lifestyle), brings an additional risk of both hepatic and cardiovascular (CV) adverse clinical outcomes. The terminology of “NAFLD” is stigmatizing to some but not all patients, and a more practical one should be announced soon. Medical strategies can address both diseases simultaneously, as they have crossing pathophysiological mechanisms, mainly IR. Strategies vary from lifestyle intervention and pharmacological options, as more molecules designated for T2DM treatment may be helpful in NAFLD, to surgical procedures. This review focuses on the coexistence of NAFLD and T2DM, pointing out the utility of the appropriate terminology, its prevalence, and mortality rates among the diabetic population. Briefly, we have discussed the main pathophysiological mechanisms and the risk stratification algorithm for the development of NAFLD and nonalcoholic steatohepatitis (NASH) as well as the tools for evaluation of fibrosis. Finally, we have focused on the current therapeutic options for the treatment of NAFLD associated with T2DM.

As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment‘s pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research.