Elobixibat Versus Prucalopride in Functional Constipation: A Prospective Comparative Effectiveness Study

BACKGROUND AND AIMS: receptor agonist, represent two different therapeutic approaches targeting intestinal secretion and colonic motility. This study aimed to directly compare the efficacy of elobixibat and prucalopride in patients with FC. METHODS: In this multicentre, prospective, pragmatic study with blinded outcome assessment, adults meeting Rome IV criteria for FC and refractory to first-line treatment were enrolled after a standardized run-in period. Participants received either elobixibat or prucalopride for 8 weeks. The primary endpoint was a sustained complete spontaneous bowel movement (CSBM) response, defined as ≥ 3 CSBMs per week and an increase of ≥ 1 CSBM from baseline for at least 6 of 8 weeks. Secondary outcomes included changes in stool consistency, associated symptoms and quality of life (QoL). RESULTS: A total of 214 patients were included (elobixibat, n = 108; prucalopride, n = 106), with a mean age of 50.8 ± 17.4 years and 62.6% males. Elobixibat resulted in a significantly higher sustained CSBM response compared to prucalopride (55.6% vs. 33.9%; p = 0.024), indicating a clinically meaningful benefit. Both treatments significantly improved CSBM frequency and stool consistency; however, elobixibat showed greater improvement in key symptom domains, including straining (p < 0.001), abdominal discomfort (p = 0.005), bloating (p = 0.011) and QoL (p = 0.009). Both drugs were well tolerated. CONCLUSIONS: This head-to-head comparative study demonstrates that elobixibat provides superior overall symptomatic relief and quality-of-life improvement compared with prucalopride, potentially due to its dual mechanism of action. These findings support the consideration of IBAT inhibition as a second-line treatment option in patients with FC. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2025/04/085075.