Saroglitazar improves liver health in people with fatty liver disease and NASH
Saroglitazar magnesium improved various measures of liver health in a recent study of people with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
Samer Gawrieh, MD, Indiana University, presented the results of the prospective, multicenter, double-blind, randomized phase II EVIDENCES IV trial in saroglitazar at The Liver Meeting, the annual meeting of the American Association for the Study of Liver Disease, in Boston this month.
Saroglitazar is a novel, non-thiazolidinedione, non-fibric PPAR alpha-gamma double agonist that plays a role in the oxidation of free fatty acids and reduces the production of triglycerides in the liver, thereby improving insulin sensitivity and glucose metabolism. .
The study could include adults (aged 18 to 75) with a body mass index (BMI) of at least 25 (meaning they were at least overweight, if not obese), with a documented diagnosis of NAFLD within 24 months of the study screening period and a liver biopsy showing NASH or simple steatosis (accumulation of fat in the liver).
The study excluded men who drank more than three drinks per day and women who drank more than two drinks per day. It also excluded those who had experienced a weight change of more than 5% in the previous three months, had started taking vitamin E at a dose greater than 100 international units per day during the previous three months, were taking drugs containing thiazolidinedione, had altered the doses of statins. or fibrates within the past three months, had cirrhosis, or had a history of other chronic liver disease.
The study selected participants for NAFLD and NASH over a four-week period during which they had two visits. The people included in the study had to have an ALT liver enzyme level of at least 50 units per liter at both visits with a maximum variation of 30% between these two levels.
At the end of the screening period, 106 people were randomized into four groups to receive 1 milligram (26 people), 2 mg (26 people) or 4 mg (27 people) of saroglitazar or placebo (28 people) for 16 weeks.
All those in the 1 mg and 4 mg treatment groups completed the study and were included in the final analysis. In the 2 mg treatment group, five people did not complete the study, including one who did not stick to the regimen, one who withdrew from the study, and three who discontinued treatment due to adverse health events. This meant that there were 25 people in this group in the study’s safety analysis and 23 people in the overall analysis. In the placebo group, three people did not complete the study, including one who was lost to follow-up and two who withdrew from the trial. All members of this group were always included in the overall analysis.
In the placebo, 1 mg, 2 mg and 4 mg groups, changes in liver ALT enzymes during the study were an increase of 4.2% and decreases of 27.3%, 33.2% and 44, 4%, respectively. The difference in these changes between the placebo group and the saroglitazar treatment groups was statistically significant, meaning that it was unlikely to be the result of chance.
Thereafter, the difference between the figures cited for the placebo group compared to those cited for the saroglitazar treatment groups is statistically significant, unless otherwise indicated. If any of the treatment groups is not mentioned, it means that there was no significant difference in these groups with regard to the outcome in question.
The proportion of participants in the placebo, 1 mg, 2 mg, and 4 mg groups who had at least a 25% reduction in their ALT levels was 17.9%, 73.1%, 73.9% and 70.4%, respectively. The proportion that showed at least a 50% reduction in ALT was 3.57% in the placebo group and 51.9% in the 4 mg group.
The placebo group experienced a 0.3% drop in liver fat content while the 4 mg group experienced a 4.2% drop. The proportion of these two groups who experienced a reduction of more than 20% in liver fat content was 16.0% and 48.2%, respectively. The proportion that saw a decline of more than 30% was 8.0% and 40.7%.
Fasting insulin decreased by an average of 6.1 and 13.8 microunits per milliliter in the placebo and 4 mg groups, respectively. Treatment did not have a significant association with changes in fasting glucose or HbAlc levels.
Triglycerides increased by 1.9 mg per deciliter in the placebo group and decreased by 29.6 mg per dl in the 4 mg group. HDL cholesterol decreased by 0.3% in the placebo group and increased by 10.9% in the 4 mg group. The treatment had no significant impact on total cholesterol or LDL cholesterol.
Those in the placebo group experienced a 22.0% increase in their APRI score (an indicator of the likelihood of advanced fibrosis or cirrhosis), while the 1 mg, 2 mg, and 4 mg groups experienced a decrease of 19. 4%, 23.2% and 27.6% their marks, respectively. Improved liver fibrosis test scores increased 3.9% in the placebo group and decreased 2.5% in the 4 mg group. The treatment had no significant impact on CK-18 (a biomarker of NASH) or liver stiffness.
Treatment with saroglitazar had no significant effect on creatinine levels or BMI.
Saroglitazar was generally well tolerated. Two people experienced serious adverse health events, both of which were considered unrelated to treatment. A person who stopped treatment did so for a reason considered likely to be related to the treatment: a mild rash on the abdomen and neck.
There were no deaths or cardiovascular health events in the study.
“Saroglitazar magnesium 4 mg significantly improved serum ALT, hepatic steatosis, insulin resistance and [irregular blood lipids] in patients with elevated baseline NAFLD / NASH and ALT, âthe study authors concluded.
To read the summary of the conference, Click here.