Teduglutide

Overview

GLP-2 is an intestinotrophic hormone secreted by enteroendocrine L-cells that stimulates growth of the intestinal mucosa. Native GLP-2 is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4); teduglutide's Ala-to-Gly substitution at position 2 confers DPP-4 resistance, extending its half-life enough for once-daily subcutaneous dosing.

In the pivotal 24-week STEPS trial, teduglutide 0.05 mg/kg/day produced a clinically meaningful (20–100%) reduction in weekly parenteral support in 63% of patients versus 30% on placebo, and earlier work in Gut established its ability to reduce parenteral nutrition and IV fluid requirements. Some patients achieve enteral autonomy (independence from parenteral support) over long-term treatment.

Because it stimulates cell proliferation, teduglutide carries warnings around colorectal polyps/neoplasia, and patients require colonoscopic surveillance. Other adverse effects include abdominal pain, injection-site reactions, fluid overload, and stoma complications.

Mechanism of Action

GLP-2 receptors are expressed on intestinal subepithelial cells rather than directly on enterocytes; receptor activation drives paracrine signaling (including IGF-1 and keratinocyte growth factor) that promotes epithelial proliferation and reduces apoptosis. The net effect is a larger, more absorptive intestinal surface plus slowed gastric emptying and reduced secretion, which together lessen dependence on parenteral support in short bowel syndrome. DPP-4 resistance from the Ala2→Gly substitution is what makes sustained once-daily dosing possible.