Targeted Ileal Bile Acid Transporter Inhibition as Rescue Therapy for Tirzepatide-Induced Severe Constipation: A Case...

Constipation is a common, dose-dependent adverse effect of incretin-based anti-obesity therapies that affects patient adherence and may necessitate discontinuation, resulting in loss of metabolic benefits and weight regain. Elobixibat, an ileal bile acid transporter (IBAT) inhibitor, may offer a targeted alternative when conventional laxatives fail.

A 56-year-old woman with obesity (95 kg; BMI 38.5 kg/m²) developed severe constipation after increasing tirzepatide to 10 mg weekly. Her bowel movements decreased from 6 to 8 times weekly (Bristol Stool Chart types 3-5) to 2-3 times weekly (types 1-2), with worst symptoms 2-3 days post-injection. Lactulose, psyllium, stimulant laxatives, and polyethylene glycol were ineffective or poorly tolerated, leading to painful perianal fissures. Tests showed hypertriglyceridemia and mild transaminitis with no obstruction on imaging. Elobixibat was started at 10 mg daily before dinner with continued tirzepatide. Bowel movement occurred 20 h after the administration. Stool frequency improved to 5-6 times weekly initially and 9-10 times weekly in the second week. Transient loose stools resolved after reducing elobixibat to 5 mg daily. By week three, bowel movements normalized to 7-8 times weekly (types 3-5) with improved defecation and resolved perianal symptoms. No serious adverse events were observed.

Elobixibat provided effective relief, enabling the continuation of tirzepatide therapy. Therefore, a prospective evaluation is recommended. IBAT inhibition may represent a mechanism-based strategy to overcome the specific motility deficits induced by incretin therapy.