Ipragliflozin L-Proline

Skin disorders occur more frequently with sodium‐dependent glucose cotransporter type 2 (SGLT2) inhibitors than with other antidiabetic drugs. We conducted basic research using ipragliflozin, with the aim of identifying new measures to prevent skin disorders caused by SGLT2 inhibitors.

db/db type 2 diabetes model mice were orally administered ipragliflozin (10 mg/kg or 30 mg/kg) once a day for 28 days and skin function genes were analysed by real‐time RT‐PCR or Western blotting.

No difference in the expression level of collagen (Col1a1 and Col1a2) in the skin was detected between the ipragliflozin treatment group and the control group. On the other hand, the expression levels of enzymes involved in the synthesis and decomposition of hyaluronic acid (Has2 and Hayl1) and enzymes involved in the synthesis and decomposition of ceramide (Sptlc1, Sptlc2, Asah1, and Acer1) were significantly decreased by the administration of ipragliflozin. Furthermore, the expression levels of filaggrin (Flg), loricrin (Lor), elastin (Eln), and aquaporin‐3 (Aqp3) in the skin were lower in the ipragliflozin treatment group than in the control group.

It was revealed that ipragliflozin reduces the expression of genes involved in skin barrier and moisturizing functions, which this may be one of the mechanisms through which this drug causes skin disorders.

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with type 2 diabetes mellitus (T2DM), contributing to increased liver-related complications and cardiovascular risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as potential treatments offering benefits for both metabolic and liver-related outcomes. This systematic review evaluated the efficacy of SGLT2 inhibitors in improving hepatic steatosis, liver enzymes, glycemic control, and liver histology in patients with T2DM and NAFLD. The review was conducted using a structured methodology, including systematic database searches and risk of bias assessments. Included randomized controlled trials (RCTs) investigated various SGLT2 inhibitors, such as dapagliflozin, empagliflozin, ertugliflozin, and ipragliflozin. Most studies showed significant reductions in liver fat content, improvements in serum liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)), and favorable effects on blood pressure, triglycerides, and body composition. Glycemic control markers, including glycated hemoglobin (HbA1c), fasting glucose, and insulin resistance indices, also improved. One biopsy-based study demonstrated histological improvements, including reduced fibrosis and resolution of nonalcoholic steatohepatitis (NASH). No serious adverse events were reported. These findings suggest SGLT2 inhibitors may offer dual benefits for managing both diabetes and fatty liver disease. Further long-term studies focusing on liver histology as a primary endpoint are needed to confirm these effects.