Teduglutide, a novel glucagon-like peptide 2 analog, in the treatment of patients with short bowel syndrome

Abstract

Short bowel syndrome results from surgical resection, congenital defect or disease-associated loss of absorption. Parenteral support (PS) is lifesaving in patients with short bowel syndrome and intestinal failure who are unable to compensate for their malabsorption by metabolic or pharmacologic adaptation. Together, the symptoms of short bowel syndrome and the inconvenience and complications in relation to PS (e.g. catheter-related blood steam infections, central thrombosis and intestinal failure associated liver disease) may impair the quality of life of patients. The aim of treatment is to maximize intestinal absorption, minimize the inconvenience of diarrhea, and avoid, reduce or eliminate the need for PS to achieve the best possible quality of life for the patient. Conventional treatments include dietary manipulations, oral rehydration solutions, and antidiarrheal and antisecretory treatments. However, the evidence base for these interventions is limited and treatments that improve the structural and functional integrity of the remaining intestine are needed. Teduglutide, an analog of glucagon-like peptide 2, improves intestinal rehabilitation by promoting mucosal growth and possibly by restoring gastric emptying and secretion, thereby reducing intestinal losses and promoting intestinal absorption. In a 3-week, phase II balance study, teduglutide reduced diarrhea by around 700 g/day and fecal energy losses by around 0.8 MJ/day. In two randomized, placebo-controlled, 24-week, phase III studies, similar findings were obtained when evaluating the fluid composite effect, which is the sum of the beneficial effects of teduglutide – reduction in the need for PS, increase in urine production and reduction in oral fluid intake. The fluid composite effect reflects the increase in intestinal fluid absorption (and the concomitant reduction in diarrhea) and may be used in studies in which metabolic balance assessments are not performed. In studies of up to 24 weeks’ duration, teduglutide appears to be safe and well tolerated. Treatment with teduglutide was associated with enhancement or restoration of the structural and functional integrity of the remaining intestine with significant intestinotrophic and proabsorptive effects, facilitating a reduction in diarrhea and an equivalent reduction in the need for PS in patients with short bowel syndrome and intestinal failure.