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. 2019 Oct 11;20(20):5055. doi: 10.3390/ijms20205055

Table 5.

Summary of the clinical evidence of PPAR agonists in liver diseases.

Disease Target Drug Name Clinical Phase (Sample Size) Main Findings/Primary Endpoint Reference/Clinical Trial Identifier
NAFLD PPARα Gemfibrozil NA (46)

  • ▪ Decreased liver enzymes

 [178]
Fenofibrate NA (16)

  • ▪ Decreased liver enzymes, hepatocellular ballooning degeneration, and triglycerides

 [179]
NA (27)

  • ▪ Reduced triglycerides, VLDL, and APOB

 [180]
Pemafibrate II-ongoing (100)

  • ▪ Primary endpoint: Hepatic fat fraction and adverse events

 NCT03350165
PPARγ Pioglitazone NA (18)

  • ▪ Improved biochemical and histological features of NASH

 [185]
IV (55)

  • ▪ Reduced liver enzymes and hepatic fat content

  • ▪ Improved histological features of NASH

 [186]
NA (74)

  • ▪ Reduced liver enzymes

  • ▪ Reduced hepatocellular injury, Mallory–Denk bodies and fibrosis

 [187]
III (247)

  • ▪ Reduced liver enzymes

  • ▪ Reduced hepatic steatosis and lobular inflammation

 [188]
IV (101)

  • ▪ Improved biochemical and histological features of NASH

 [189]
NA (10)

  • ▪ Improved ALT levels, mild histological improvement

 [190]
Rosiglitazone NA (30)

  • ▪ Improved insulin sensitivity

  • ▪ Decreased in liver enzymes and fat content

  • ▪ No change to triglyceride level.

 [191]
II (63)

  • ▪ Improved steatosis, insulin sensitivity and AST/ALT levels

 [192]
II (44)

  • ▪ No improvement in fibrosis, ballooning and steatosis.

  • ▪ Maintained insulin sensitivity and AST/ALT levels.

 [193]
NA (74)

  • ▪ Reduced plasma insulin and improved HOMA-IR score.

  • ▪ Decrease in AST and ALT

  • ▪ Improved NAFLD activity score

 [194]
NA (47)

  • ▪ No change in rate of steatosis and fibrosis

  • ▪ Diet together with exercise was superior to rosiglitazone alone.

 [195]
dual PPAR α/δ Elafibranor II (276)

  • ▪ Resolved NASH without fibrosis worsening

 [196]
III-ongoing (2000)

  • ▪ Primary endpoint: Achieving resolution of NASH without worsening of fibrosis

 NCT02704403
Dual-PPAR α/γ Saroglitazar III-unknown status (100)

  • ▪ Primary endpoint: Change in NAFLD fibrosis score

 NCT02265276
II-ongoing (106)

  • ▪ Primary endpoint: Percentage change from baseline in serum ALT levels

 NCT03061721
II-ongoing (15)

  • ▪ Primary endpoint: Change in NAFLD activity score with no worsening of fibrosis

 NCT03863574
II-ongoing (60)

  • ▪ Primary endpoint: Change in hepatic fat content

 NCT03617263
II-ongoing (15)

  • ▪ Primary endpoint: Number of participants with adverse events

 NCT03639623
Lobeglitazone IV (38)

  • ▪ Reduced hepatic fat content

  • ▪ Improved glycemic, liver, and lipid profiles

 [197]
Pan-PPAR Lanifibranor II-ongoing (225)

  • ▪ Primary endpoint: Responder analysis based on the improvement of the SAF (steatosis: S, activity: A, and fibrosis: F) activity score

 NCT03008070
II-ongoing (84)

  • ▪ Primary endpoint: Intrahepatic triglyceride level

 NCT03459079
PBC PPARα Bezafibrate III (100)

  • ▪ Normalization of bilirubin, liver enzymes, albumin, and plasma triglyceride levels.

 [202]
NA (16)

  • ▪ Decreased levels of liver enzymes

 [203]
NA (66)

  • ▪ Improved biliary enzyme parameters

 [204]
III-ongoing (34)

  • ▪ Primary endpoint: Complete biochemical response

 NCT02937012
III-ongoing (84)

  • ▪ Primary endpoint: Proportion of patients with a reduction in itch intensity of 50% or more

 [217]
Fenofibrate II (20)

  • ▪ Decrease in liver enzymes, IgM, IL-1, and IL-6

  • ▪ No significant decrease in bilirubin

 [206]
NA (22)

  • ▪ Decrease in liver enzymes, cholesterol, and TG

  • ▪ No significant effect on serum bilirubin

 [208]
NA (120)

  • ▪ Improvement in ALP, ALT, AST and decompensation, and transplant-free survival

 [209]
II (10)

  • ▪ Decrease in total cholesterol, TG, VLDL, LDL, and liver enzymes

 [210]
PPARβ/δ Seladelpar III-ongoing (240)

  • ▪ Primary endpoint: Complete biochemical response

 NCT03602560
II & III-ongoing (356)

  • ▪ Primary endpoint: Adverse events, and treatment emergent adverse events

 NCT03301506
II-ongoing (116)

  • ▪ Primary endpoint: Serum alkaline phosphatase, adverse events

 NCT02955602
II (41)

  • ▪ Normalization of ALP. Risk of grade 3 increase in aminotransferases

 [211]
Dual PPAR α/δ Elafibranor II (45)

  • ▪ Primary endpoint: Relative change from baseline in serum alkaline phosphatase

 NCT03124108
Dual PPAR α/γ Saroglitazar II-ongoing (36)

  • ▪ Primary endpoint: Improvement in ALP levels

 NCT03112681
Hepatitis C PPARγ Farglitazar II (265)

  • ▪ No evidence of antifibrotic activity

 [212]
Pioglitazone II (5)

  • ▪ No satisfactory viral response.

 [213]
II (40)

  • ▪ Decreased serum HCV RNA.

 [214]
IV (80)

  • ▪ Increased rapid virologic response

 [215]