Table 5.
Studies on the impact of SGLT-2i on NAFLD in patients with T2DM.
| Study | Study Design | No of Pts | SGLT-2i/Drug Used (No of Pts) |
Control Group | Treatment Duration (Weeks) |
NAFLD Diagnosis ** |
Key Results |
|---|---|---|---|---|---|---|---|
| Eriksson, J., et al., 2018 [150] | Randomised, double-blind, prospective | 84 | Dapagliflozin (42) | OM-3CA or placebo | 12 | MRI | Reduction of serum transaminases, CK-18, FGF-21 in Dapagliflozin group and liver fat in Dapagliflozin + OM-3CA group |
| Kahl, S., et al., 2020, [161] | Randomised, double-blind, prospective | 84 * | Empagliflozin (42) | Placebo | 24 | MRI | LFC improvement only in empagliflozin |
| Chehrehgosha, H., et al., 2021 [165] | Randomised, double-blind, prospective | 78 | Empagliflozin (21) | Pioglitzone or placebo | 24 | TE | Better CAP, LS, no difference vs. pioglitzone for serum transaminases or FIB-4 |
| Gaborit, B., et al., 2021 [167] | Randomised, double-blind, prospective | 34 | Empagliflozin (18) | Placebo | 12 | MRI | Reduction in liver fat vs. placebo |
| Bando, Y., et al., 2017 [145] | Randomised, open label, prospective | 62 | Ipragliflozin (40) | SOC | 12 | C/T | Improvement in serum transaminases. VFA, L/S ratio compared to SOC |
| Ito, D., et al., 2017 [147] | Randomized, open label, prospective | 66 | Ipragliflozin (32) | Pioglitazone | 24 | C/T or U/S | Improvement of L/S ratio, ALT, ferritin not statistically significant between 2 groups; ipragliflozin more weight and VFA reduction |
| Kuchay, M.S., et al., 2018 [152] | Randomized, open label, prospective | 42 | Empagliflozin (22) | SOC | 20 | MRI | Reduction of liver fat and ALT |
| Shibuya, T., et al., 2018 [154] | Randomized, open label, prospective | 32 | Luseogliflozin (16) | Metformin | 26 (6 months) |
C/T or U/S | Improvement in L/S ratio compared to baseline |
| Shimizu, M., et al., 2019 [155] | Randomized, open label, prospective | 57 | Dapagliflozin (33) | SOC | 24 | U/S | Improvement of CAP and LS, especially for high LS at the trial beginning |
| Han, E., et al., 2020 [160] | Randomized, open label, prospective | 44 | Ipragliflozin (+metformin +pioglitazone) (29) |
Metformin + pioglitazone | 24 | U/S | Better FLI, CAP, NAFLD liver fat score |
| Kinoshita, T., et al., 2020 [162] | Randomized, open label, prospective | 98 | Dapagliflozin (32) | Pioglitazone (33) Glimepiride (33) | 28 | C/T | Improvement of L/S ratio and ALT with pioglitazone and dapagliflozin |
| Takahashi, H., et al., 2021 [168] | Randomized, open label, prospective | 55 | Ipragliflozin (27) | SOC, except pioglitazone, GLP1 | 72 | LB | Statistically significant improvement in NASH resolution and fibrosis improvement in SGLT-2i vs. SOC |
| Yoneda, M., et al., 2021 [169] | Randomized, open label, prospective | 40 | Topogliflozin (21) | Pioglitzone | 24 | MRI | Decrease of liver steatosis in both groups, body weight decrease in topogliflozin |
| Arai, T., et al., 2021 [164] | Open label, Prospective | 100 | Canagliflozin (29) Ipragliflozin (12) Tofogliflozin (6) Dapagliflozin (4) Luseogliflozin (4) Empagliflozin (1) |
SOC | 48 | U/S | Decrease in LS and CAP in SGLT-2i during treatment, statistically significant decrease in SGLT-2i vs SOC in ALT, FIB-4 |
| Akuta, N., et al., 2017 [146] | Single-arm, Prospective | 5 | Canagliflozin (5) | N/A | 24 | LB | Improvement of NAS score, liver steatosis; fibrosis improvement in 2 pts |
| Itani, T., et al., 2018 [151] | Single arm, Prospective | 35 | Canagliflozin (35) | N/A | 26 (6 months) | U/S | Improvement in ALT, ferritin, FIB-4 at 3 and 6 months |
| Miyake, T., et al., 2018 [153] | Single arm, Prospective | 43 | Ipragliflozin (43) | N/A | 24 | 12 LB, 41 U/S | Reduction in serum transaminases, CAP, not statistically significant reduction in fibrosis |
| Sumida, Y., et al., 2019 [156] | Single-arm, Prospective | 40 | Luseogliflozin (40) | N/A | 24 | U/S | Reduction in transaminases, serum ferritin and liver fat in MRI |
| Akuta, N., et al., 2019 [157] | Single arm, Prospective | 9 | Canagliflozin (9) | N/A | 24 | LB | Histological improvement in all patients |
| Akuta, N., et al., 2020 [159] | Single arm, Prospective | 7 | Canagliflozin (7) | N/A | 24 | LB | Histopathological improvement at 24 weeks sustained to >1 year, transaminases and ferritin better at 24 weeks |
| Seko, Y., et al., 2017 [148] | Retrospective | 45 | Canagliflozin (18) Ipragliflozin (6) |
Sitagliptin | 24 | LB | Significant decrease in serum transaminases with both drugs, not statistically significant between SGLT-2i and sitagliptin |
| Choi, D.H., et al., 2018 [149] | Retrospective | 102 (all abnormal ALT) | Dapagliflozin + Metformin (50) | DPP4 + Metformin | 44.4 ± 18.4 for dapagliflozin and 50.4 ± 21.6 for DPP4 | U/S | Statistically significant decrease in dapagliflozin vs. DPP4 |
| Yamashima, M., et al., 2019 [158] | Retrospective | 22 | Ipragliflozin (18) Dapagliflozin (2) Tofogliflozin (1) Empagliflozin (1) | N/A | 52 (22 pts) and 104 (15 pts) | 12 LB, 10 U/S | Lower serum transaminases levels at 12 and 24 months, better CAR and shear wave velocity at 12 months |
| Yano, K., et al., 2020 [163] | Retrospective | 69 | Dapagliflozin (10) Canagliflozin (7) Ipragliflozin (3) Empagliflozin (2) |
SOC | 162 | LB | Improvement of serum transaminases in both groups (No head to head comparison) |
| Euh, W., et al., 2021 [166] |
Retrospective | 283 | Dapagliflozin (58) Empagliflozin (34) Ipragliflozin (3) |
SOC, except GLP-1 and Insulin | 39 | U/S | Statistically significant reduction in ALT and body weight in SLT2i vs. SOC |
* All patients with excellent glycemic control. ** Test used to diagnose/assess NAFLD.Abbreviations: RCT: Randomised controlled trial, L/S ratio: Liver to spleen ratio, VFA: Visceral fat area, C/T: Computed tomography, MRI: Magnetic Resonance Imaging, OM-3CA: omega-3 carboxylic acids, LFC: Liver fat content, FIB-4: Fibrosis-4 index, ALT: Alanine aminotransferase, FLI: Fatty liver index, CAP: Controlled attenuation parameter, SGLT-2i: Sodium-glucose co-transporter type-2 inhibitors, NAS score: NAFLD Activity Score, LB: Liver biopsy, GLP-1: Glucagon-like peptide-1, pts: patients.