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

BACKGROUND AND AIMS: The choice of second-line therapy in functional constipation (FC) is often empirical, owing to the lack of direct comparisons between agents with distinct mechanisms of action. Elobixibat, an ileal bile acid transporter inhibitor, and prucalopride, a selective 5-HT4 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.