Researchers writing in Diabetes Care this month report that empagliflozin, a sodium–glucose cotransporter 2 inhibitor (SGLT2), successfully reduced liver fat content in recent-onset and metabolically well-controlled type 2 diabetes (T2D).
This could be good news for diabetes patients who develop nonalcoholic fatty liver disease, which is associated with cardiovascular disease, chronic kidney disease, retinopathy, steatosis, fibrosis, and cirrhosis. While weight loss can effectively address nonalcoholic fatty liver disease, it can be difficult to achieve. Currently, the condition is treated with glucagon-like peptide 1 receptor agonists, thiazolidinediones and novel therapies, such as, pegbelfermin and elafibranor, but to date, there is no one accepted treatment for nonalcoholic fatty liver disease.
SGLT2 inhibitors like empagliflozin improve glycemia by increasing urinary glucose excretion, but also reducing body weight and blood pressure leading to improved cardiovascular and renal function.
This study, by Michael Roden, M.D. of Leibniz Institute for Diabetes Research at Heinrich-Heine University in Germany, included 84 patieints with type 2 diabetes of approximately three years. They were randomly assigned to a 24-week treatment course of 25 mg daily empagliflozin or placebo.
There was 2.3-fold greater reduction in liver fat from baseline to 24 weeks for patients treated with empagliflozin.
There were no differences between the two groups in adipose tissue insulin resistance and insulin-stimulated free fatty acids suppression at low- and high-insulin conditions.
The primary end point was the difference of the change in liver fat content from baseline to 24 weeks. Tissue-specific insulin sensitivity was the secondary outcome.
Researchers also found that empagliflozin also decreased uric acid levels and adiponectin levels even without a change in insulin sensitivity.
"Because future nonalcoholic fatty liver disease treatment in T2D will require strategies that simultaneously address the different mechanisms underlying metabolic liver disease, EMPA could serve as a partner for such combination treatments because of its favorable effects on liver fat and body weight," the authors wrote.
Sabine Kahl, Sofiya Gancheva, Klaus Straßburger, et al. "Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial." Diabetes Care. February 2020. https://doi.org/10.2337/dc19-0641