Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non- Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common reasons of enzyme increase in liver. In About 10 percent of patients with NAFLD, the disease progresses toward Non Alcoholic Steatohepatitis (NASH) and about one third of them may progress toward cirrhosis, liver dysfunction, and even hepatocellular carcinoma.ObjectivesAccording to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease, the aim of this study was to assess the effects of metformin, pioglitazone, and silymarin on treatment of NAFLD.Patients and MethodsSixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital, Qazvin, Iran, were assigned randomly into three groups (n = 22). First group was treated by pioglitazone 15 mg/d, second group by metformin 500 mg/d, and third group by silymarin 140 mg/d. All patients underwent clinical and biochemical evaluations including weight, fasting blood sugar (FBS), lipid profiles, body mass index (BMI), aspartate aminotransferase (AST ), alanine aminotransferase (ALT), and serum insulin levels in pre- and post-intervention after eight-week follow up.ResultsBefore the treatment there was no significant difference between three groups with respect to average age, BMI and gender, FBS, lipid profile, AST, ALT, serum insulin level, and Homeostasis Model Assessment (HOMA) index for insulin resistance. After the intervention, a significant reduction was observed in average amount of FBS, lipid profile, ALT, AST, serum insulin level and HOMA index in three groups (P < 0.01). The most reduction in average FBS, TG, serum insulin level, and HOMA index was observed in pioglitazone group, the most reduction in average amount of cholesterol was seen in metformin group, and the most decrease in average amount of AST and ALT occurred in silymarin group.ConclusionsThese results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD. Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups.

The potential of silymarin for the treatment of hepatic disorders

“…Several groups have been interested in examining the potential of silymarin in the treatment of NAFLD/ NASH. In three comparative trials silymarin has been tested against placebo, in one against vitamin E, and in one against pioglitazone and metformin (Summary in Table 4, [98][99][100][101][102]). Furthermore, three Italian groups conducted open trials applying silymarin combined with other agents (see Additional file 3).…”

“…Although the number of participants, doses and period of treatment were different, both trials revealed a tendency to reduce ALT/ AST levels in silymarin treated patients [99,101]. In comparison to pioglitazone and metformin, silymarin also caused a more significant change in ALT/AST levels [102]. However, the effect of silymarin on triglycerides, fasting blood sugar, and insulin levels was rather weak compared to pioglitazone treatment [102].…”

“…In comparison to pioglitazone and metformin, silymarin also caused a more significant change in ALT/AST levels [102]. However, the effect of silymarin on triglycerides, fasting blood sugar, and insulin levels was rather weak compared to pioglitazone treatment [102]. Thus, the effect of silymarin on insulin and other metabolic parameters in the liver is an open question.…”

Nuclear Receptors as Therapeutic Targets in Liver Disease: Are We There Yet?

“…For instance, rosiglitazone, a PPARγ agonist, in combination with fenofibrate, a PPARα agonist, was in clinical trial, but owing to the small number of participants, the clinical trial was terminated (33). Currently, among many thiazolidinediones, pioglitazone is the only drug that is considered to be an effective therapeutic agent for improving NAFLD (34). Pioglitazone, in combination with Berberine (a plant alkaloid that lowers cholesterol), is in Phase II clinical trial.…”

Non Alkolik Yağlı Karaciğer Hastalığında Güncel Medikal Tedavi

“…Yağ depolanmasına ilave olarak başlayan inflamasyonu, giderek şiddetlenen ileri inflamasyon ve balonlaşma dejenerasyonu takip eder. Bu süreç devam ederse; fibroz, mallory cisimciği ve sirozu takiben karaciğer yetmezliği gelişir (4,5).…”