Dapagliflozin Plus Omega-3 Carboxylic Acids for Non-Alcoholic Fatty Liver Disease in T2D

Combination treatment with dapagliflozin plus omega-3 carboxylic acids may reduce fat content in nonalcoholic fatty liver disease.

Combination therapy with dapagliflozin and omega-3 carboxylic acids reduced liver fat content in individuals with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), according to findings published in Diabetologia.

Although there is some evidence that the use of sodium-glucose co-transporter 2 inhibitors may have a positive effect on liver fat and hepatocyte injury biomarkers in type 2 diabetes and NAFLD, there have been no completed placebo-controlled studies. The current randomized placebo-controlled double-blind parallel-group clinical trial included 84 participants with type 2 diabetes and NAFLD who were randomly assigned to 1 of 4 treatments: 10 mg dapagliflozin (n=21), 4 g omega-3 carboxylic acids (n=20), a combination of both (n=22), or placebo (n=21).

The study’s primary endpoint was liver fat content, as evaluated by magnetic resonance imaging (proton density fat fraction).The total liver volume, markers of glucose and lipid metabolism, and hepatocyte injury and oxidative stress were assessed at baseline and on trial completion after 12 weeks of treatment.

Liver proton density fat fraction was significantly reduced from baseline in all groups except placebo (relative changes: omega-3 carboxylic acids, −15%; dapagliflozin, −13%; omega-3 carboxylic acids + dapagliflozin, −21%). The combination regimen was the only regimen that reduced both liver proton density fat fraction and total liver fat volume (relative change, −24%) vs placebo. Dapagliflozin monotherapy lowered the levels of hepatocyte injury biomarkers, and when used alone and combined with OM3CA, glucose control was improved and body weight and abdominal fat volumes were reduced. There was no effect on fatty acid oxidative stress biomarkers with any treatment. The NAFLD fibrosis score had no significant change with the effect of treatment on liver proton density fat fraction.

Related Articles

There was a significant decrease in HbA1c from baseline in participants using dapagliflozin monotherapy only. There was no treatment effect of omega-3 carboxylic acids treatment on fasting and 2-hour plasma glucose concentrations.

“The study met its primary objective and provides proof of concept for this dual therapy to reduce liver fat in individuals with type 2 diabetes and NAFLD,” wrote the authors.


Eriksson JW, Lundkvist P, Jansson PA, et al. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study. Diabetologia. 2018;61(9):1923-1934.