Efficacy of Empagliflozin in Patients with Mild-to-Moderate Ulcerative Colitis: A Randomized Controlled Pilot Study

Abstract Ulcerative colitis (UC) is a relapsing-remitting inflammatory bowel disease characterized by chronic mucosal inflammation of the colon. Preclinical evidence suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin, exert anti-inflammatory and antioxidant effects through activation of the adenosine monophosphate-activated protein kinase (AMPK) pathway. This randomized, double-blind, placebo-controlled pilot study aimed to evaluate the clinical efficacy, safety, and biomarker modulation of adjunctive empagliflozin in patients with mild-to-moderate UC. A total of 60 adult patients were allocated (1:1) to receive either standard background therapy plus placebo or standard therapy plus empagliflozin (25 mg orally once daily) for 6 months. The primary composite endpoints were improvements in disease activity (Montreal grade response and remission) and health-related quality of life (SF-36 score). Secondary endpoints included changes in serum tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), AMPK, fecal calprotectin, number of daily stools, hemoglobin, and erythrocyte sedimentation rate (ESR). Following 6 months of intervention, empagliflozin treatment significantly reduced serum TNF-α, CRP, and fecal calprotectin levels compared to placebo (P < 0.01). Serum AMPK levels showed marked upregulation in the empagliflozin group (P < 0.001). Patients receiving empagliflozin demonstrated a significantly higher clinical response rate (93.3% vs. 66.6%, P = 0.001) and clinical remission rate (63.3% vs. 46.7%, P = 0.001) based on the Montreal classification. Significant improvements were also observed in SF-36 scores (68.6 vs. 58.2, P = 0.008), number of daily stools (2.3 vs. 4.8, P < 0.001), hemoglobin (12.8 vs. 11.1 g/dL, P < 0.001), and ESR (18.4 vs. 34.5 mm/1st hr, P < 0.001). Adverse events were minimal and comparable between the study arms. In conclusion, adjunctive empagliflozin therapy demonstrated significant clinical benefit, improved quality of life, and attenuated both systemic and mucosal inflammatory biomarkers in mild-to-moderate UC, likely mediated via AMPK pathway activation. Clinical Trial Registration Registered at ClinicalTrials.gov (Identifier NCT05610956).