Apraglutide, a novel glucagon‐like peptide‐2 analog, improves fluid absorption in patients with short bowel syndrome intestinal failure: Findings from a placebo‐controlled, randomized phase 2 trial

Abstract

PB Jeppesen has served as a consultant and speaker for VectivBio AG and was the principal investigator in this study. J Eliasson served as a consultant for VectivBio AG and was a study investigator. MK Hvistendahl and N Freund were study investigators. F Bolognani and C Meyer are employees of VectivBio AG.

Apraglutide, a novel once‐weekly glucagon‐like peptide‐2 analog, improves intestinal fluid and energy absorption in patients with short bowel syndrome: An open‐label phase 1 and 2 metabolic balance trial

“…2,39 Apraglutide's beneficial impact on fluid absorption has also been confirmed in another recently published phase 2 trial in which fluid absorption was assessed indirectly by increases in urine production. 41 The magnitude of effects of once-weekly apraglutide on fluid, energy, and electrolyte absorption were comparable to those previously reported for daily native GLP-2, teduglutide, and glepaglutide treatment. 2,38,40 Apraglutide is the first GLP-2 analog to significantly improve absorption of energy across the whole patient spectrum in the SBS population when measured by bomb calorimetry, the gold standard laboratory method for quantifying intestinal energy absorption.…”

“…For the first time, our study shows that beneficial effects can be achieved through once‐weekly treatment; previous phase 2 trials of other GLP‐2 agonists required daily injections 2,39 . Apraglutide's beneficial impact on fluid absorption has also been confirmed in another recently published phase 2 trial in which fluid absorption was assessed indirectly by increases in urine production 41 …”

“…Fat mass estimation errors by DXA may occur because of variations in soft tissue hydration 43 . Contrary to this trial, the phase 2 trial of apraglutide showed more diverse effects on body composition, with no uniform pattern of change 41 . This difference emphasizes that short‐term changes in body composition should be interpreted with care and may vary because of individual patient characteristics and evaluation methods.…”

Complementary and antagonistic effects of combined glucagon‐like peptide‐2 and glucagon‐like peptide‐1 receptor agonist administration on parameters relevant to short bowel syndrome

“…However, the present study establishes that not only are these effects on intestinal growth additive, but they occur only in response to a specific dose ratio of GLP‐2R and GLP‐1R agonism. Of note, it is possible that one of the benefits of apraglutide, a very‐long‐acting GLP‐2R agonist currently under investigation, may be mediated through its ability to enhance both villus height and SI length, thus increasing the surface area for fluid absorption in patients with SBS 32,34 . However, the ability to achieve maximal intestinal growth in association with lower doses of a GLP‐2R agonist may prove beneficial in preventing some of the side effects associated with existing GLP‐2–based therapies 1–5 …”

“…Of note, it is possible that one of the benefits of apraglutide, a very-long-acting GLP-2R agonist currently under investigation, may be mediated through its ability to enhance both villus height and SI length, thus increasing the surface area for fluid absorption in patients with SBS. 32,34 However, the ability to achieve maximal intestinal growth in association with lower doses of a GLP-2R agonist may prove beneficial in preventing some of the side effects associated with existing GLP-2-based therapies. [1][2][3][4][5] As compared with GLP-2R agonists, which do not affect either GE or GI transit, GLP-1 mimetics potently slow both of these parameters, thereby increasing the time available for nutrient and fluid absorption.…”