SGLT2 Inhibition Beyond Glycemic Control: Dapagliflozin's Role in Nonalcoholic Steatohepatitis

<p><span>Dapagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor primarily used for type 2 diabetes mellitus (T2DM), has recently emerged as a potential therapeutic option for nonalcoholic steatohepatitis (NASH). Preclinical studies indicate that dapagliflozin reduces hepatic steatosis by modulating lipogenic and inflammatory pathways, including FXR/SHP/LXRα/SREBP-1c and NF-κB signaling. Clinical trials in patients with NASH, particularly those with T2DM, demonstrate improvements in liver enzymes, insulin resistance, hepatic fat content, and fibrosis scores. A recent randomized controlled trial involving biopsy-confirmed NASH showed significant histological improvement in steatosis, ballooning, and fibrosis with dapagliflozin compared to placebo. Meta-analyses further support reductions in liver transaminases, body weight, and hepatic fat fraction. These findings suggest that dapagliflozin exerts benefits beyond glycemic control by targeting key mechanisms underlying NASH progression. However, large multicenter studies in non-diabetic populations and long-term data on liver-related outcomes are still required. This review summarizes current evidence and mechanistic insights into dapagliflozin’s role in NASH management</span><span lang="EN-IN">.</span><span lang="EN-IN"> </span></p>