GLP-2 analog · short bowel syndrome
Apraglutide is an experimental, long-acting synthetic analog of GLP-2, a gut hormone that helps maintain the intestinal lining. It is being developed for short bowel syndrome with intestinal failure (SBS-IF), in which people cannot absorb enough fluid and nutrients and rely on intravenous (parenteral) support.
GLP-2 is a hormone secreted by the small intestine that acts on GLP-2 receptors, supporting nutrient absorption and growth of the intestinal lining. Natural GLP-2 is broken down and cleared within minutes. Apraglutide keeps potency and selectivity at the GLP-2 receptor comparable to the natural hormone but is cleared far more slowly and binds strongly to blood proteins; in rats, its elimination half-life was about 159 minutes, compared with 6.4 minutes for natural GLP-2 and 19 minutes for teduglutide, an approved GLP-2 analog1.
In rats this longer exposure produced more small-intestine growth than the comparison peptides when doses were spaced further apart1. The aim in people is to increase how much fluid and nutrition the remaining bowel absorbs, reducing reliance on intravenous support.
In a small crossover phase 2 trial, eight adults with SBS-IF produced more urine during apraglutide periods than during placebo, a sign of better fluid absorption from the gut2. In a 52-week open-label study of nine patients whose colon remained connected, parenteral support volume fell by about half, seven patients gained at least one day a week off intravenous support, and MRI showed longer measured small-bowel length3.
In the phase 3 STARS trial, 163 patients were randomized 2:1 to apraglutide or placebo; parenteral support volume at 24 weeks fell 25.5% versus 12.5% from baseline, with a larger gap in patients with a stoma, while 48-week secondary endpoints in patients with colon-in-continuity did not reach significance4. A second placebo-controlled phase 3 trial began recruiting in 20265.
Apraglutide is not approved anywhere; it remains in phase 3 development5.
In the phase 2 crossover trial, treatment-related events were mild to moderate and included increased urination, reduced stoma output, stoma complications, reduced thirst and swelling (edema), with no serious events judged drug-related2. The 52-week study reported mostly mild to moderate events3, and STARS investigators described it as well tolerated4. Longer-term data are still being collected in an open-label extension study6.
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