Ipragliflozin improves the hepatic outcomes of patients with diabetes with NAFLD
Open accessAbstract
Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m2, P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18). of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects. (Hepatology Communications 2022;6:120-132) . Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m2, P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18). of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects. (Hepatology Communications 2022;6:120-132) .
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Ipragliflozin significantly improved hepatic fibrosis and MASH resolution compared with standard care.
“ipragliflozin, an SGLT2i, significantly improved hepatic fibrosis and MASH resolution compared with standard care.”
From Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages (2026) · cites this paper as [221]
The histological-results section reports significantly more fibrosis-stage improvement with ipragliflozin than with control after 72 weeks (57.1% versus 16%; P=0.01). It reports MASH resolution in 66.7% of participants who had it at baseline, versus 27.3% in the control group, but does not establish that this difference was statistically significant. The limitations discussion says the sample was too small to confirm superiority for MASH resolution. (LLM, conf=0.90)
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Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages
Aquino, J. B. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1792423 · Cited by 1 · see citing works
- Authors
- Takahashi, H., Kessoku, T., Kawanaka, M., Nonaka, M., Hyogo, H., Fujii, H., Nakajima, T., Imajo, K., Tanaka, K., Kubotsu, Y., Isoda, H., Oeda, S., Kurai, O., Yoneda, M., Ono, M., Kitajima, Y., Tajiri, R., Takamori, A., Kawaguchi, A., Aishima, S., Kage, M., Nakajima, A., Eguchi, Y., & Anzai, K.
- Affiliations
- Saga University (JP)
- Yokohama City University (JP)
- Kawasaki Medical School (JP)
- Hiroshima General Hospital (JP)
- Osaka City University (JP)
- Sapporo Kosei General Hospital (JP)
- Osaka City Juso Hospital
- Tokyo Women's Medical University (JP)
- Kurume University (JP)
- ORCID
- Venue
- Diabetes mellitus
- Publisher
- Endocrinology Research Centre
- Published
- 2025-05-23
- Volume
- 28
- Issue
- 2
- Pages
- 210-227
- ISSN
- 2072-0351 (ISSN-L)
- 2072-0378
- OpenAlex
- W4410750468
- Cited by
- 1
- References
- 50
- Citations by year
- 2026: 1
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Diabetes Mellitus (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- ipragliflozin, SGLT2 inhibitors, non-alcoholic fatty liver disease, type 2 diabetes, nonalcoholic steatohepatitis, liver fibrosis, glycemic control, obesity, liver pathology, pioglitazone, glucagon-like peptide-1 analogues, insulin therapy, HbA1c, body mass index, NAFLD prevention
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