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Empagliflozin as First Line in Patients with Type 2 and Fatty Liver Disease

Oct 13, 2018
 
Editor: Joy Pape, MSN, FNP-C, CDE, WOCN, CFCN, FAADE

Author: Melissa Bailey, Pharm.D. Candidate, USF College of Pharmacy

Multiple studies find drug to be first diabetes medication to show significant reduction of liver fat and suggest empagliflozin as first line therapy.

Recent studies are suggesting immediate use of empagliflozin as first line therapy for people with type 2 who have nonalcoholic fatty liver disease (NAFLD). Empagliflozin works by inhibiting the sodium-glucose cotransporter 2, promoting the excretion of glucose in the urine and improving insulin resistance.

Dr. Mohammad Kuchay and colleagues found this mechanism downregulates and reduces fatty acid synthesis in the liver of patients with nonalcoholic fatty liver disease (NAFLD) in the E-LIFT trial.

Dr. Kuchay found that 50-70% of patients with type 2 are also diagnosed with NAFLD, which can cause further complications, such as scarring and cirrhosis of the liver. The E-LIFT trial examined 50 randomized patients with T2D and NAFLD taking either 10 mg of empagliflozin, or standard of care treatments. After treatment with empagliflozin for 20 weeks, a significant reduction of liver fat (4.9%) was found by using a magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) for liver fat mapping (noninvasive technique). The control group did not show a significant reduction in liver fat (only 0.9%). They also found the reduction in HbA1c to be similar in both groups.

Currently, the only recommendation to reduce liver fat in patients with type 2 is initiating an intense low caloric diet (< 853 calories daily) and losing a significant amount of weight. However, the E-LIFT study showed no correlation between weight reduction and the reduction of liver fat, making it easier for patients who are not ready to make certain lifestyle changes to reduce NAFLD.

Another study conducted by Naveed Sattar examined six randomized trials that involved empagliflozin. Researchers used two key enzymes — alanine aminotransferase (ALT) and aspartate aminotransferase (AST) — in each trial to measure the reduction of fat in the liver from baseline. These enzymes correlate with the amount of liver fat. The EMPA-REG OUTCOME trial analyzed 7,020 patients taking either empagliflozin, glimepiride, or a placebo. Patients taking empagliflozin had a significant decrease in ALTs and ASTs after 28 weeks from baseline. Those patients who showed higher levels of ALTs and ASTs at baseline had larger reductions.

At this time, first line treatment for T2D is metformin and there is no medication approved for patients with T2D who have NAFLD. Dr. Kuchay presents this matter as an urgent public health issue and believes empagliflozin has a high potential of becoming approved for patients with T2D and NAFLD in the near future.

Practice Pearls:

  • A majority of people with type 2 diabetes are known to have nonalcoholic fatty liver disease (NAFLD), which can lead to liver scarring and cirrhosis.
  • Empagliflozin is the first diabetes medication to show a significant reduction of liver fat in patients with T2D in multiple studies.
  • Similar reductions in HbA1c and glucose levels were observed in patients taking empagliflozin compared with other diabetes medications.
  • Empagliflozin may soon be approved for the treatment of NAFLD in patients with T2D.

References:

Kuchay, M S, 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. Aug 2018, 41 (8) 1801-1808; doi: 10.2337/dc18-0165

Zinman, Bernard et al. “Rationale, Design, and Baseline Characteristics of a Randomized, Placebo-Controlled Cardiovascular Outcome Trial of Empagliflozin (EMPA-REG OUTCOMETM).” Cardiovascular Diabetology 13 (2014): 102. PMC. Web. 10 Aug. 2018.