The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease

Abstract

Background and objectiveThe prevalence of non-alcoholic fatty liver disease (NAFLD) is 60% in patients with type 2 diabetes mellitus (T2DM). NAFLD can lead to non-alcoholic steatohepatitis (NASH), both of which are the leading causes of cirrhosis. This study was undertaken to evaluate whether empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, reduces liver fat content in these patients after therapy. MethodsAfter enrolling patients of T2DM with NAFLD, they were administered empagliflozin 10 mg once daily orally for six months without modifying existing oral hypoglycemic agents (OHA) if any. All demographic data were collected, and anthropometric measurements, as well as laboratory investigations, were performed, and controlled attenuation parameter (CAP) and liver stiffness (LS) were measured using FibroScan® (Echosens, Paris, France) at baseline, and six months of therapy. The adverse effects related to therapy were also taken into account. ResultsThere was a significant decrease in mean CAP value from 282.07 ± 47.29 dB/m to 263.07 ± 49.93 dB/m and LS from 5.89 ± 4.23 kPa to 5.04 ± 1.49 kPa along with a significant decrease in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) among the patients. Compared to the baseline, there was a significant reduction in post-treatment weight, body mass index (BMI), and blood pressure (BP). The most commonly observed adverse effects of the therapy were urinary tract infection (UTI) (17.8%), nasopharyngitis (11.9%), and hypoglycemia (10.71%). ConclusionA reduction in hepatic fat content was seen in our prospective study cohort after six months of empagliflozin therapy. Empagliflozin also led to beneficial effects such as weight loss and reduction in transaminases and GGT. Given the absence of significant side effects of the therapy, empagliflozin could be used as an effective treatment modality for T2DM patients with NAFLD, which are two conditions commonly seen in combination.

In a Prediabetic Model, Empagliflozin Improves Hepatic Lipid Metabolism Independently of Obesity and before Onset of Hyperglycemia

“…Several animal studies involving diabetic and obese rodents, although notable for their exclusion of lipotoxic intermediates, have observed decreased TAG in the liver after empagliflozin treatment [ 12 , 13 ]. In one human study involving diabetic subjects, empagliflozin treatment reduced liver fat content [ 25 ]. Intrahepatic accumulation of fatty acids induces insulin resistance and endoplasmic reticulum stress [ 26 ], two factors previously implicated in the intracellular mechanism of lipid accumulation and hepatic steatosis development.…”

Efficacy and safety of guanabenz acetate treatment for non-alcoholic fatty liver disease: a study protocol for a randomised investigator-initiated phase IIa study

“…In addition, because the judgement of fat deposition depends on the collection site of the liver biopsy, MRI-PDFF, which enables easy quantitative evaluation, is considered appropriate. 8–11 …”

“…In contrast, image evaluation using MRI-PDFF has been indicated as stable and highly reproducible. In addition, because the judgement of fat deposition depends on the collection site of the liver biopsy, MRI-PDFF, which enables easy quantitative evaluation, is considered appropriate 8–11…”

“…In addition, because the judgement of fat deposition depends on the collection site of the liver biopsy, MRI-PDFF, which enables easy quantitative evaluation, is considered appropriate. [8][9][10][11] The 24-week MOZART (Magnetic Resonance Imaging and Elastography in Ezetimibe Versus Placebo for the Assessment of Response to Treatment in NASH) trial explored the correlation between histological changes by liver biopsy and hepatic fat content using MRI-PDFF to examine the effect of ezetimibe on NASH. The trial reported an estimated cut-off point of -3.46% for changes in liver fat content from baseline that optimally distinguished between histological responders and nonresponders.…”

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

“…Compared to baseline measurements in patients with NASH, body weight, hemoglobin A1c (HbA1c), hepatic function indexes (AST, ALT, and GGT), body fat mass, and steatosis were significantly decreased after Ipragliflozin oral administration (50 mg/day) for 24 weeks. 176 , 177 Empagliflozin, another SGLT2 inhibitor was analyzed in several clinical trials (Institutional Review Board of NAMS (approval number: 547-077/078), 178 NCT02964715, IRCT20190122042450N3). 179 After Empagliflozin administration for 6 months, there was a significant reduction in the mean controlled attenuation parameter (CAP) value from 282.07 ± 47.29 to 263.07 ± 49.93 dB/m and liver stiffness (LS) from 5.89 ± 4.23 to 5.04 ± 1.49 kPa.…”