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Empagliflozin’s Effect on Liver Fat

Aug 18, 2018
 

An SGLT-2 inhibitor, empagliflozin reduces liver fat and ALT levels in people who have type 2 diabetes.

Type 2 diabetes is often present with non-alcoholic fatty liver disease (NAFLD). NAFLD is also an independent risk factor for other disease states besides type 2 diabetes, such as cardiovascular disease and chronic kidney disease. A common key factor in the pathogenesis of both type 2 diabetes and NAFLD is insulin resistance. Many diabetes medications have been tested to treat both diabetes and NAFLD, including empagliflozin, a sodium glucose cotransporter-2 inhibitor (SGLT-2). Because SGLT-2 inhibitors promote urinary glucose excretion to lower blood glucose levels, they ultimately improve insulin resistance in patients who have type 2 diabetes. Because insulin resistance is improved with SGLT-2 inhibitors, empagliflozin was studied to evaluate its effect on liver fat, ALT, AST, and GGT levels in patients with type 2 diabetes and NAFLD.  

The E-LIFT trial was a prospective, open-label, randomized clinical study that examined the effect of empagliflozin on patients who have type 2 diabetes and NAFLD. The study population included patients who were seen at Medanta-The Medicity Hospital endocrine outpatient clinic in India. Patients were included in the study if they were 20 years old or older, had documented hepatic steatosis, and had an HbA1c >7% to <10%. Exclusion criteria was HbA1c>10%, alcohol intake more than 30 grams/day, or evidence of other forms of liver disease, including cirrhosis and hepatitis B and C. Hepatic steatosis was measured MRI proton density fat fraction (MRI-PDFF). Patients were randomized in a 1:1 ratio; 22 patients went into the study group where they received 10 mg of empagliflozin daily and 20 patients went into the control group where they received standard treatment for type 2 diabetes.

All participants were of Indian descent and forty percent of the patients were women.

The primary outcome measure of the study was a change in amount of liver fat from baseline to the end of the 20-week trial. Secondary outcomes were the ALT, AST, and GGT levels.

Empagliflozin was found to reduce liver fat significantly compared to the control group. The empagliflozin group achieved a reduction in fat from 16.2% to 11.3% (p<0.0001). The change in liver fat from 16.4% to 15.5% was found in the control group (p<0.054). Compared to baseline, the empagliflozin group had a significant reduction in AST levels (64.3 to 49.7 IU/L; p 0.001). The two groups together showed significant differences in serum ALT (-10.9 IU/L; p =0.005). Changes in GGT levels were not significant (-11 IU/L; p = 0.057). Adverse events reported included one case of balanoposthitis after one week of initiation of empagliflozin, nonspecific fatigue after five days of initiation, and one case of arthralgia that improved shortly after discontinuation.

In conclusion, a daily dose of 10 mg of empagliflozin reduces liver fat in patients with type 2 diabetes and NAFLD. Because non-alcoholic fatty liver disease is associated with insulin resistance and type 2 diabetes, correcting glycemia to improve insulin resistance will improve NAFLD. Empagliflozin has shown to be a good option to treat both type 2 diabetes and NAFLD.

Practice Pearls:

  • Non-alcoholic fatty liver disease often coexists with type 2 diabetes.
  • Insulin resistance is a key factor in the pathogenesis of both NAFLD and type 2 diabetes.
  • Treatment with an SGLT-2 inhibitor such as empagliflozin can improve insulin resistance and therefore help reduce  AST and ALT levels in patients with NAFLD.

Reference:

Kuchay, Mohammad Shafi, et al. “Effect of Empagliflozin on Liver Fat in Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial).” Diabetes Care, vol. 41, no. 8, Dec. 2018, pp. 1801–1808., doi:10.2337/dc18-0165.

Amanda Cortes LECOM School of Pharmacy PharmD Candidate C/O 2019

 

SGLT-2 inhbitors have additional benefits in addition to how empagliflozin reduces liver fat. To learn more,  visit our SGLT-2 Therapy center.