Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2: Effects on Intestinal Morphology and Absorption, Renal Function, Bone and Body Composition, and Muscle Function

Abstract

Background and aims. In a short-term study, Glucagon-like peptide 2 (GLP-2) has been shown to improve intestinal absorption in short bowel syndrome (SBS) patients. This study describes longitudinal changes in relation to GLP-2 treatment for two years. Methods. GLP-2, 400 micrograms, s.c.,TID, were offered, to eleven SBS patients keeping parenteral support constant. 72-hour nutritional balance studies were performed at baseline, weeks 13, 26, 52 during two years intermitted by an 8-week washout period. In addition, mucosal morphometrics, renal function (by creatinine clearance), body composition and bone mineral density (by DEXA), biochemical markers of bone turnover (by s-CTX and osteocalcin, PTH and vitamin D), and muscle function (NMR, lungfunction, exercise test) were measured. Results. GLP-2 compliance was >93%. Three of eleven patients did not complete the study. In the remaining 8 patients, GLP-2 significantly reduced the fecal wet weight from approximately 3.0 to approximately 2.0 kg/day. This was accompanied by a decline in the oral wet weight intake, maintaining intestinal wet weight absorption and urinary weight constant. Renal function improved. No significant changes were demonstrated in energy intake or absorption, and GLP-2 did not significantly affect mucosal morphology, body composition, bone mineral density or muscle function. Conclusions. GLP-2 treatment reduces fecal weight by approximately 1000 g/d and enables SBS patients to maintain their intestinal fluid and electrolyte absorption at lower oral intakes. This was accompanied by a 28% improvement in creatinine clearance.

Randomised controlled trial of colostrum to improve intestinal function in patients with short bowel syndrome

“…However, in a similar setting, it has been possible to demonstrate significant improvements in intestinal function employing other treatment modalities, and therefore, the effects of colostrum seem to be so modest that the clinical relevance is negligible. 20,21,43 In fact, two of the eight patients showed a negative value for relative improvement of intestinal absorption; the other six had improvements, though mainly minor, in the magnitude of 2-3%, and one patient improved his relative absorption with 11% from 47 to 58%.…”

Exogenous GLP-2 and IGF-I induce a differential intestinal response in IGF binding protein-3 and -5 double knockout mice

“…In our rat model of short bowel syndrome we have noted that GLP-2 increases small intestine length (21), an important goal of rehabilitation therapy in patients with intestinal failure (20). Thus, given the therapeutic potential of GLP-2 to improve intestinal adaptation (13,19), further studies are needed to investigate the role of IGFBP-3/-5 in the growth of muscularis and subsequent lengthing of the bowel in response to GLP-2.…”

“…Moreover, GLP-2 is considered a key mediator of intestinal adaptive growth through stimulation of epithelial cell proliferation and inhibition of apoptosis (7,11,17,31). Clinical studies evaluating native GLP-2 and (Gly 2 )GLP-2, a degradation-resistant analog of GLP-2, demonstrate improved intestinal morphology and absorption in humans with intestinal failure (13,19), and studies have been conducted or are underway to evaluate the efficacy of GLP-2 in Crohn's disease (22) and other conditions of intestinal dysfunction (www. npsp.com).…”

GLP-2: What do we know? What are we going to discover?

“…It showed that the exogenous administration of GLP-2 stimulates small intestinal growth during weaning in neonatal pigs without polyps or unusual growths in the intestine [56]. It is of interest to note that the authors administered a dose of 40 μg/kg/day, in two subcutaneous injections a day, which is twice that of a pharmacological dose of GLP-2 used in the majority of adult human trials [57][58][59][60]. They reported that the effects were limited to the gastrointestinal tract and it was well tolerated with no measurable changes in activity, growth, development, renal and hepatic function, or growth in non-gastrointestinal tissues [56].…”