Ipragliflozin L-Proline

Nonalcoholic fatty liver disease (NAFLD) is a global health concern associated with dyslipidemia, obesity, and type 2 diabetes mellitus (T2DM), necessitating effective therapeutic strategies. Sodium-glucose transporter 2 (SGLT-2) inhibitors have shown promise in improving metabolic parameters, but their comparative efficacy in NAFLD remains unclear.

We systematically searched PubMed, Cochrane Library, Scopus, and Embase for randomized controlled trials (RCTs) up to 31 December 2024, involving NAFLD patients treated with SGLT-2 inhibitors versus placebo or standard treatments. Outcomes included changes in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, BMI, and HbA1c. A Bayesian NMA was performed using a random-effects model, with mean differences (MD) and 95% credible intervals (CrI) reported. Treatments were ranked using Surface Under the Cumulative Ranking Curve (SUCRA) scores.

We evaluated and compared the efficacy of SGLT-2 inhibitors in improving lipid profiles (LDL-C, HDL-C, total cholesterol, and triglycerides), BMI, and HbA1c in patients with NAFLD. Eleven RCTs involving 805 patients were included. Empagliflozin achieved the greatest LDL-C reduction (MD: −8.07 mg/dL, 95% CrI: −25.92 to 1.41; SUCRA: 95.38%), total cholesterol reduction (MD: −15.08 mg/dL, 95% CrI: −58.87 to 5.38; SUCRA: 94.32%), and HbA1c reduction (MD: −0.69%, 95% CrI: −1.52 to −0.06; SUCRA: 81.84%). Ipragliflozin non-significantly increased HDL-C (MD: 2.28 mg/dL, 95% CrI: −1.21 to 4.83; SUCRA: 85.11%) and significantly reduced triglyceride (MD: −22.39 mg/dL, 95% CrI: −39.25 to −7.27; SUCRA: 82.26%). Dapagliflozin resulted in significant BMI reduction (MD: −1.23 kg/m2, 95% CrI: −2.11 to −0.41; SUCRA: 73.28%).

Empagliflozin and ipragliflozin demonstrated superior efficacy in improving lipid profiles, while dapagliflozin was most effective for BMI reduction in NAFLD patients. These findings align with their cardiovascular and metabolic benefits, offering a multifaceted approach to a complex disease. Further research is needed to confirm long-term effects and optimize treatment strategies for diverse NAFLD populations.

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.