Optimization of glucose control drives improvement of NAFLD independent of weight loss in people with T2D

Aim. The mainstays for the treatment of non-alcoholic fatty liver disease (NAFLD) are lifestyle intervention with the aim of significant weight loss alongside aggressive cardiovascular risk reduction. NAFLD is tightly associated with both obesity and type 2 diabetes (T2D). In people with T2D, glucose lowering agents that promote weight loss have shown a beneficial impact on NAFLD based on histological features. However, it remains unclear as to whether glucose lowering can improve NALFD in patients with T2D, independent of weight loss. Methods. In a consecutively recruited population of 637 patients with T2D with HbA1c levels above treatment targets, DPP-IV inhibition, GLP-1RA therapy or SGLT2 inhibition was initiated, alongside lifestyle education with maintenance of exiting background glucose lowering treatment. We examined the longitudinal impact of the optimization of glycaemic control on fatty liver index (FLI) and Fibrosis score 4 (Fib-4) adjusting for changes in BMI and choice of glucose lowering regimen over a 12-month period. Results. Change in HbA1c and change in FLI correlated significantly in a linear regression analysis after adjustment for change in BMI, age, sex, and drug class (R=0.467, p=0.031). The greatest reduction in FLI was observed in patients with the largest reduction in HbA1c (p<0.0001). The probability of improvements in FLI with optimization of glycaemic control was similar with all 3 glucose lowering agents, despite differences in weight reduction. Similar relationships were observed examining the changes in glycaemic control and Fib-4. Conclusions. Significant reductions of HbA1c are associated with improvement in NAFLD independently from weight loss. These results suggest a prominent role for the optimization of glucose control in the management of coexistent NAFLD and T2D, especially in the ‘lean’ NAFLD and where significant weight loss may not be achieved.