Dapagliflozin + Omega-3 Carboxylic Acids Lower Liver Fat in Type 2 Diabetes NAFLD
BOSTON, MA—Combined dapagliflozin (DAPA) and free omega-3 fatty acid carboxylic acids (OM-3 CA) significantly reduced liver fat, according to a 12-week double blind study presented at The Liver Meeting® 2016.
“The combination of DAPA and OM-3 CA resulted in a significant reduction in percentage and total liver fat, while the monotherapies resulted in numerically smaller and non-significant reductions compared to placebo,”noted lead study author Jan Oscarsson, MD, PhD, of AstraZeneca R&D, in Mölndal, Sweden. “This study suggests beneficial effects of SGLT2 inhibition alone or in combination with OM-3 CA on non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes.”
“DAPA had unique effects on measures of hepatocyte injury, which was not evident in the combination therapy group indicating that effects on liver fat reduction and hepatocyte damage biomarkers are not necessarily associated,” Dr. Oscarsson noted.
DAPA, a sodium-glucose co-transporter 2 (SGLT2) inhibitor works by increasing glucose loss in urine, and reducing HbA1c and body weight. Inhibition of SGLT2 also leads to greater fatty acid oxidation. OM-3 CA is a mixture of polyunsaturated free fatty acids, mainly eicosapentaenoic (EPA) and docosahexaenoic acid (DHA).
The study authors sought to evaluate the effects of DAPA and OM-3 CA, both individually and in combination, on liver fat content in patients with type 2 diabetes (T2D) and NAFLD compared with placebo.
“T2D patients with BMI >25kg/m2, liver fat >5.5% on stable metformin and/or sulfonylurea treatment were randomized to placebo (n=21), 10mg DAPA (n=21), 4g OM-3 CA OD (n=20) or the combination of DAPA and OM-3 CA (n=22) once daily,” Dr. Oscarsson reported. A total of 75 patients completed the trial.
At baseline and Week 12, liver and adipose tissue fat content were assessed by magnetic resonance imaging (MRI). Patients underwent a 75g glucose tolerance test (OGTT).
“All active treatments significantly reduced liver fat percentage from baseline,” reported Dr. Oscarsson. “The relative reduction in liver fat percentage for the combination (DAPA+OM-3 CA) was significant (-21%, adjusted P=0.046), but not significant for DAPA (-13%) or OM-3 CA (-15%) alone, as compared to placebo (-3%).”
Change in total liver fat volume was similar to changes in liver fat percentage, “suggesting that the change in liver fat percentage was not secondary to changed hepatic water volume,” the researchers found.
Body weight and abdominal subcutaneous and visceral fat volumes all declined among patients in the DAPA and DAPA+OM-3 CA study arms. Glucose control (HbA1c levels, fasting glucose) improved in these patients, as well.
Levels of biomarkers of hepatocyte damage (AST, ALT, CK-18 [M30 and M65] and gGT) declined in patients receiving DAPA, but not OM-3 CA or combined DAPA+OM-3 CA when compared to placebo.
“All adverse events were mild or moderate in intensity and as expected from previous studies with these treatments,” the coauthors noted.