In type 2 diabetes patients with co-existing metabolic dysfunction-associated fatty liver disease (MAFLD), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2i) was superior to other antidiabetic drugs like pioglitazone.¹

Mino et al retrospectively analysed data of 568 patients with MAFLD and type 2 diabetes. Of these, 210 were taking treatment for their diabetes: 95 were on SGLT2is, 86 were on pioglitazone, while 29 were taking both. Through this study, they aimed to compare the effects of these antidiabetic drugs on liver disease measured via a change in fibrosis measured by the Fibrosis-4 (FIB-4) Index at 96 weeks from the baseline.

The mean FIB-4 index showed a substantial decline from 1.79 at baseline to 1.56 at 96 weeks among patients on SGLT2i. However, a similar reduction was not observed among patients taking pioglitazone. A significant decrease in the aspartate aminotransferase to platelet ratio index (APRI), serum aspartate and alanine aminotransferase (ALT), hemoglobin A1c and fasting blood sugar was seen in both groups. The reduction in ALT in the SGLT2i group was -17 vs -14 in the pioglitazone group. Patients taking pioglitazone registered an increase in their body weight by 1.7kg compared to the SGLT2i group, where a decrease of -3.2 kg was observed. However, categorizing patients according to their baseline ALT (>30 IU/L) saw a significant reduction in the FIB-4 index in all patients. When an SGLT2i was added to pioglitazone treatment, an improvement in the liver enzymes but not FIB-4 index was seen.

At present, the American Association for the Study of Liver Disease (AASLD)² and European Association for the Study of the Liver and European Association for the Study of Diabetes (EASL-EASD)³ recommend only pioglitazone for the treatment of type 2 diabetes patients with NAFLD.

This study highlights that the beneficial effects of SGLT2is extend beyond glycemic control. In type 2 diabetes patients with MAFLD, SGLT2i treatment not only improved blood glucose, but was also superior to pioglitazone in improving fatty infiltration and liver fibrosis by reducing body weight.

References

1. Masaaki Mino, et al. Effects of sodium glucose cotransporter 2 inhibitors and pioglitazone on FIB-4 index in metabolic associated fatty liver disease. Hepatol Res. 2023 Mar 11. doi: 10.1111/hepr.13898.
2. Naga Chalasani, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 Jan;67(1):328-357. doi: 10.1002/hep.29367.
3. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004.