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Kashmiri endocrinologist shows new medicine reduces liver fat

Wednesday, June 13, 2018

A research led by Kashmiri endocrinologist, Dr M Shafi Kuchay has found that addition of empagliflozin, a new anti-diabetes medicine, to standard diabetes treatment for patients with type-2 diabetes and non-alcoholic fatty liver disease (NAFLD) produces reductions in liver fat and improvements in liver enzymes.

The research has been published in topmost journal of American Diabetes Association, Diabetes Care and was carried out in Division of Endocrinology and Diabetes, Medanta, The Medicity Hospital Gurugram, India. Dr Kuchay was the lead researcher for the study.
“Fatty liver disease is a public health problem and an increasingly recognised association of diabetes,” said Dr Kuchay, consultant in Medanta. He noted that NAFLD progresses to steatohepatitis (NASH) and eventually to cirrhosis or even cancer in a significant proportion of patients. 

“Pharmacologic treatment modalities are few,” he continued, “No agent is approved by the FDA for treating this condition. Empagliflozin, an antidiabetic drug belonging to the SGLT-2 inhibitor class, has gained popularity in recent years because of its ability to promote weight loss and reduce the rate of cardiac events in high-risk patients with type 2 diabetes”. 

Dr Kuchay and his colleagues randomly assigned 50 patients with type 2 diabetes and NAFLD to treatment with empagliflozin 10 mg daily combined with standard treatment of type 2 diabetes or to standard treatment for diabetes without the addition of empagliflozin. This was an open-label trial that lasted for 20 weeks. 

The addition of empagliflozin to standard diabetes treatment was associated with a reduction in liver fat as measured by MRI-derived proton density fat fraction, with a mean difference between the two groups of 4.0 percent (P<0.0001). 

In addition, there was a significant reduction in liver fat from baseline to the end-of-treatment, from 16.2% to 11.3% (P < 0.0001) among empagliflozin-treated patients. In contrast, among those who did not receive empagliflozin, the reduction in liver fat only trended toward significance (from 16.4% to 15.5%; P = 0.057). 

Those treated with empagliflozin also experienced a 10.9 IU/L greater reduction in alanine aminotransferase (ALT) and a 7.7 IU/L greater reduction in aspartate aminotransferase (AST) than those on standard therapy alone. The difference was only significant for ALT, however (P = 0.005 for ALT and P = 0.212 for AST). There was also a trend towards a greater reduction in gamma-glutamyltranspeptidase with empagliflozin (11 IU/L; P = 0.057). 

“This is the first study that showed that this drug reduces liver fat and if the use of this agent, or others of this class, is confirmed to have beneficial effects on all the stages of NAFLD, it will enable physicians to target multiple complications of diabetes with a single drug,” said Dr. AmbrishMithal, Chairman, Division of Endocrinology and Diabetes, Medanta Hospital. 

He pointed out, however, that it remains to be seen whether empagliflozin treatment will ultimately delay or prevent chronic liver disease in a larger group of patients. It will also be important to evaluate how the agent affects histopathological changes at various stages of fatty liver disease. Finally, it will be interesting to see if fatty liver disease can be addressed using empagliflozin in patients without type 2 diabetes.

This study was earlier presented at the annual meeting of the Endocrine Society, from March 17 to 20, in Chicago, where it was widely covered by international media. Subsequently, it was also published by Medscape, a famous professional website for healthcare providers.