Table 1.
Antidiabetic and lipid metabolism drugs under clinical trials
| Class | Drug classification | Drug name | Registered clinical trails | Outcome | Ref. |
|---|---|---|---|---|---|
| Antidiabetic drugs (PPAR signaling) | PPARγ agonists | Pioglitazone | Phase 4 (NCT00994682) |
↓Liver fibrosis ↓Insulin resistance ↓Liver TG |
140,141 |
| PPARα/δ agonists | Elafibranor (GFT505) |
Phase 3 (NCT02704403) Phase 2b (NCT01694849) |
↓Liver fibrosis ↓Inflammation ↓Liver enzymes, lipids, glucose profiles |
143 | |
| PPARα/γ agonists | Saroglitazar | Phase 2 (NCT03061721) |
↓Insulin resistance ↓Liver fibrosis ↓Plasma ALT, liver fat content |
573 | |
| PPARα agonists | Pemafibrate (K-877) | Phase 2 (NCT03350165) |
↓MRE-based liver stiffness. ↓ ALT, LDL-C No decrease in liver fat content |
574 | |
| Fenofibrate | Phase 2 (NCT02781584, NCT02354976) |
↓Serum triglycerides No decrease in liver fat |
575,576 | ||
| PPARδ agonists | Endurobol (GW501516) | Phase 2 (NCT00388180) |
↓VLDL, LDL, IDL ↑HDL |
577,578 | |
| Seladelpar | Phase 2 (NCT03551522) |
No effect on hepatic steatosis ↓ALT, AST, GGT, AP |
579 | ||
| PPARα/δ/γ agonists | Lanifibranor (IVA337) |
Phase 3 (NCT04849728, recruiting) Phase 2b (NCT03008070) |
↓Liver fibrosis ↓Hepatic steatosis ↓Liver enzyme levels ↓Inflammation |
146 | |
| Antidiabetic drugs (GLP-1 agonists) | GLP agonist | Exenatide |
Phase 4 (NCT01208649, NCT02303730) Phase 2 (NCT00529204) |
↓Hepatic steatosis ↓ALT, AST, GGT ↓Blood glucose |
580,581 |
| Liraglutide | Phase 2 (NCT01237119, NCT02654665) |
↓Hepatic steatosis ↑Glucose control ↓Body weight |
154,156,582 | ||
| Semaglutide | Phase 2 (NCT02453711, NCT02970942) |
↓Hepatic steatosis ↓Body weight |
158,162 | ||
| Glucagon/GLP-1 dual agonist | BI 456906 | Phase 2 (NCT04771273, recruiting) | No results posted | ||
| GIP/GLP-1 receptor agonist | Tirzepatide (LY3298176) | Phase 2 (NCT03131687) |
↓ALT, AST ↓Keratin-18, procollagen III ↑Adiponectin |
163,164 | |
| GLP-1-glucagon-GIP receptor tri-agonist | HM15211 |
Phase 1 (NCT03744182) Phase 2 (NCT04505436, recruiting) |
↓Body weight | 583 | |
| Balanced glucagon-GLP-1 receptor agonist | Cotadutide |
Phase 2b (NCT03235050) Phase 2 (NCT04019561, ongoing) |
↓Liver fibrosis ↓Hepatic steatosis ↓Body weight ↓ALT, AST |
166 | |
| GCGR and GLP-1R dual agonist | Oxyntomodulin (OXM, JNJ-6456511) | Phase 1 (NCT01055340 NCT01373450) |
↓Body weight ↓Serum TC, TG, LDL-C ↑Insulin secretion |
584–586 | |
| DPP-4 inhibitor | Sitagliptin | Phase NA (NCT01260246) |
↓Hepatic steatosis ↓Body weight ↓ALT, AST, GGT, LDL |
587 | |
| SGLT2 inhibitors | Empagliflozin |
Phase 4 (IRCT20190122042450N3, NCT02637973, NCT02686476, NCT02964715) Combined therapy (NCT04639414, NCT03646292) |
↓Liver fibrosis ↓Hepatic steatosis ↓Insulin resistance ↓ALT, AST |
178–180,588 | |
| Dapagliflozin |
Phase 3 (NCT03723252, recruiting) Phase 2 (NCT02279407) Phase 1 (NCT02696941) |
↑Glucose control ↓Body weight, abdominal fat ↓ALT, AST, GGT ↓CK18-M30, CK18-M65, FGF21 |
184,589 | ||
| Dapagliflozin |
UMIN000022155 UMIN000023574 |
↓Liver fibrosis ↓Hepatic steatosis ↓Body weight ↓ALT, GGT |
182,183 | ||
| Canagliflozin |
UMIN000023044 UMIN000020615 |
↓Hepatic steatosis ↓Insulin resistance ↓Body weight ↓ALT, AST, GGT |
181,590 | ||
| Ipragliflozin |
UMIN000015727 UMIN 000022651 jRCTs071180069 UMIN000029697 |
↓Liver fibrosis ↓Body weight, abdominal fat ↓ALT, AST, HbA1c |
176,177 | ||
| Tofogliflozin | jRCTs031180159 |
↓Hepatic steatosis ↓Body weight ↓ALT, AST, GGT, HbA1c ↓CK18-M30, ↑HDL |
591 | ||
| Luseogliflozin | UMIN000016090 |
↓Hepatic steatosis ↓Body weight |
592 | ||
| Lipid metabolism | Acetyl-ACC inhibitor | Firsocostat (GS-0976) |
Phase 2 (NCT02856555) Phase 2b (NCT03449446) |
↓Liver fibrosis ↓Hepatic steatosis ↓ALT |
85,86,570 |
| PF-05221304 | Phase 2a (NCT03248882) combined therapy (NCT03776175, NCT04321031, recruiting) |
↓Hepatic steatosis ↑Plasma TG (co-administration with a DGAT2 inhibitor could address increased TG) |
88 | ||
| MK-4074 | Phase 1 (NCT01431521) |
↓Hepatic steatosis ↑Plasma TG |
87 | ||
| Allosteric inhibitor of ACC1 and ACC2 | NDI-010976 | Phase 1 (NCT02876796) | ↓DNL | 89 | |
| Fatty acid synthetase (FAS) inhibitor | Orlistat | Phase 4 (NCT00160407) |
↓Hepatic steatosis ↓Body weight ↓Insulin resistance ↓ALT, AST ↑Adiponectin |
93 | |
| TVB-2640 |
Phase 2 (NCT03938246) Phase 2b (NCT04906421, recruiting) |
↓Hepatic steatosis ↓Liver fibrosis ↓Inflammation |
91 | ||
| FT-4101 | Phase ½ (NCT04004325, terminated) | ↓Hepatic steatosis | 92 | ||
| SCD inhibitor | Aramchol |
Phase 3 (NCT04104321, recruiting) Phase 2 (NCT01094158, NCT02279524) |
↓Hepatic steatosis ↓ALT, AST, HbA1c |
95,97 | |
| AMPK activator | PXL770 | Phase 1 (NCT03950882) |
↑Insulin sensitivity ↓GGT |
593 | |
| Downregulation of SREBP1-c expression | Oltipraz (OPZ) |
Phase 2 (NCT01373554, NCT00956098) Phase 3 (NCT02068339, NCT04142749, recruiting) |
↓Liver fat content ↓TGF-beta1 |
109,110 | |
| HMG-CoA reductase inhibitor | Atorvastatin | Phase 2 (NCT02633956) (NCT04679376, recruiting) |
↓Hepatic steatosis ↓Serum advanced glycation endproducts |
120,594 | |
| LXR and SREBP-1c inhibitor | DUR-928 | Phase 1b |
↓Hepatic steatosis ↓ALT, AST, GGT ↓TC, LDL |
595 | |
| Lipid metabolism | 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1/HSD11B1) inhibitor | RO5093151 | Phase 1b (NCT01277094) |
↓Liver fat content ↓Body weight ↓ALT, GGT, TC |
596 |
| Lipid metabolism | Hydrophilic, non-toxic, secondary bile acid in humans | Ursodeoxycholic acid (UDCA) | Phase 4 (NCT04977661) |
↓Hepatic steatosis ↓Body weight ↓ALT, AST, LDL, TG, TC ↓Inflammation |
597,598 |
| Steroidal agonist of FXR | Obeticholic acid |
Phase 3 (NCT02548351) (EudraCT, 20150-025601-6)) Phase 2b (NCT01265498) |
↓Hepatic steatosis ↓Liver fibrosis ↓ALT, AST, GGT |
202,203,599 | |
| EDP-305 | Phase 2 (NCT03421431) |
↓Liver fat content ↓ALT |
600 | ||
| Non-steroidal agonist of FXR | Tropifexor (LJN-452) | Phase 2b (NCT03517540, NCT02855164) |
↓Liver fat content ↓ALT, GGT |
599,601,602 | |
| EYP001 | Phase 2 (NCT03812029) | No results posted | 603 | ||
| Nidufexor (LMB763) | Phase 2 (NCT02913105, NCT03804879) | No results posted | 604 | ||
| Cilofexor (GS-9674) | Phase 2 (NCT02781584, NCT02854605) |
↓Hepatic steatosis ↓serum bile acids ↓GGT |
205 | ||
| THR-β agonist | Resmetirom (MGL-3196) |
Phase 3 (NCT03900429 EudraCT Number: 2018-004012-22) Phase 2 (NCT02912260) |
↓Hepatic steatosis ↓Liver fibrosis ↓LDL, APOB, TG |
218,219 | |
| VK2809 | Phase 2 (NCT02927184 NCT04173065, recruiting) |
↓Liver fat ↓LDL |
|||
| Lipid metabolism | FGF19 analog | Aldafermin (NGM282) | Phase 2 (NCT02443116, NCT02704364 NCT03912532) |
↓Hepatic steatosis ↓ALT, AST, bile acids ↓PRO-C3 |
212–214 |
| Lipid metabolism | Fibroblast growth factor 21 (FGF21) receptor agonist | Pegbelfermin (BMS-986036) | Phase 2 and 2b (NCT03486899, NCT03486912, NCT02413372, NCT02097277) |
↓Hepatic steatosis ↓serum PRO-C3 ↑adiponectin ↑HDL, ↓TG |
227,228,605 |
| Efruxifermin | Phase 2a (NCT03976401) |
↓Hepatic steatosis ↓serum PRO-C3 ↓ALT, AST, GGT, ALP |
229 |