Eriksson JW, et al. - This randomised placebo-controlled double-blind parallel-group study was performed to examine the impacts of dapagliflozin and omega-3 (n-3) carboxylic acids (OM-3CA), individually or combined, on liver fat content in people with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Researchers reported that combined treatment with dapagliflozin and OM-3CA significantly decreased liver fat content. It was noted that dapagliflozin monotherapy decreased all measured hepatocyte injury biomarkers and fibroblast growth factor 21 (FGF21), implying a disease-modifying effect in NAFLD.

Methods

• This research was performed at five clinical research centres at university hospitals in Sweden.
• For the purpose of this investigation, 84 members with type 2 diabetes and NAFLD were randomly assigned 1:1:1:1 to four treatments by a centralised randomisation system, and all members and in addition investigators and staff associated with the study conduct and analyses were blinded to treatments.
• After that, each group received oral doses of one of the following: 10 mg dapagliflozin (n = 21), 4 g OM-3CA (n = 20), a combination of both (n = 22) or placebo (n = 21).
• The primary endpoint was liver fat content evaluated by MRI (proton density fat fraction [PDFF]) and also total liver volume and markers of glucose and lipid metabolism as well as of hepatocyte injury and oxidative stress were surveyed at baseline and after 12 weeks of treatment (completion of the trial).

Results

• The study results showed that participants had a mean age of 65.5 years (SD 5.9), BMI 31.2 kg/m² (3.5) and liver PDFF 18% (9.3).
• It was observed that all active treatments significantly reduced liver PDFF from baseline, relative changes: OM-3CA, -15%; dapagliflozin, -13%; OM-3CA + dapagliflozin, -21%.
• In comparison with placebo, only the combination treatment reduced liver PDFF (p=0.046) and total liver fat volume (relative change, -24%, p=0.037).
• An interaction between the PNPLA3 I148M polymorphism and change in liver PDFF in the active treatment groups (p=0.03) was found.
• The findings demonstrated that dapagliflozin monotherapy, but not the combination with OM-3CA, decreased the levels of hepatocyte injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase (γ-GT), cytokeratin (CK) 18-M30 and CK 18-M65 and plasma fibroblast growth factor 21 (FGF21).
• It was noted that changes in γ-GT correlated with changes in liver PDFF (ρ = 0.53, p=0.02).
• Findings revealed that dapagliflozin alone and in combination with OM-3CA improved glucose control and decreased body weight and abdominal fat volumes.
• By treatments, fatty acid oxidative stress biomarkers were not affected.
• Compared with previous studies with these treatments, there were no new or unexpected adverse events.