Glucagon-like Peptide-2 Analog Research Articles

Intestinal adaptation and rehabilitation in adults with short bowel syndrome.

Over the past decade, trophic gastrointestinal hormonal factors have been included in the intestinal rehabilitation programs for short bowel syndrome (SBS). Up today the only trophic factor approved for clinical practice is the glucagon-like peptide-2 (GLP-2) analogue, teduglutide. A literature review on the last 2-year data on GLP-2 analogues for the treatment of SBS in adults has been performed. Several reports on real-world data on the efficacy and safety of teduglutide treatment for SBS, some case-reports on the use of teduglutide in non-SBS conditions as well as phase 2 trials on new GL-2 analogues on patients with SBS have been retrieved. Real-world data confirmed the teduglutide efficacy not only in weaning off IVS in accurately selected patients but also increased the alert on the risk of development of gastrointestinal polyps related to the drug; the impact of the therapy on patients' QoL deserves further studies and the cost-utility of the treatment is still uncertain. Some case reports highlighted the potential benefit of treatment with teduglutide in non-SBS gastrointestinal diseases, such as graft-versus-host disease, primary amyloidosis and refractory microscopic colitis. Phase 2 RCTs on safety and efficacy of two new long-acting GLP-2 analogues, glepaglutide and apraglutide, were published, and phase 3 RCTs have been completed.

Cholecystitis following the initiation of glucagon-like peptide-2 analogue for short bowel syndrome: A case report.

Patients with short bowel syndrome (SBS) have a risk for cholelithiasis and cholecystitis, particularly those who have received long-term parenteral nutrition (PN). Teduglutide (Revestive), a glucagon-like peptide-2 (GLP-2) analogue, is the first effective therapy approved for treating patients with SBS via self-subcutaneous injection. It also pharmacologically inhibits gallbladder contraction, which may increase the risks for cholelithiasis and cholecystitis. Here, we report a case of cholecystitis occurring after the introduction of a GLP-2 analogue in a patient with SBS and cholelithiasis. A 16-year-old girl, with a residual intestinal anatomy of 5 cm jejunum and left colon, was referred to our hospital for further treatment of SBS. She underwent jejunocolic anastomosis 2 months later. After that, she received PN for 2.5 years. Teduglutide treatment was initiated to reduce PN dependence. Several asymptomatic gallbladder stones were found during a routine ultrasound examination before drug initiation. On day 31 of teduglutide treatment, right subcostal pain with fever occurred, and the patient was diagnosed with acute cholecystitis. GLP-2 analogue treatment was temporarily discontinued. The patient underwent gallbladder drainage followed by cholecystectomy 3 weeks later. Histopathological findings illustrated mucosal hyperplasia of the gallbladder. Her postoperative course was uneventful, and teduglutide was restarted 2 weeks postoperatively. GLP-2 analogues promote gallbladder refilling and epithelial hyperplasia, which may be a risk factor for cholecystitis in patients with cholelithiasis, as observed in our patient. Based on our experience, patients with SBS and established asymptomatic cholelithiasis may be considered for prophylactic cholecystectomy before the administration of GLP-2 analogues.

Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate: a multicenter study.

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4-4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12-40) cm. The median duration of teduglutide therapy was 19 (IQR 12-36) months, with 23 patients (74%) treated for > 1year and 9 treated for > 3years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5-22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028). Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate. What is Known: • Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS. •Data about long-term therapy with teduglutide in children in real life are still scarce. What is New: • Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional. • Starting treatment with the drug at a young age is associated with a greater response rate.

Effect of the semisynthetic form of glucagon-like peptide-2 analog in an experimental model of intestinal ischemia-reperfusion injury

Effect of the semisynthetic form of glucagon-like peptide-2 analog in an experimental model of intestinal ischemia-reperfusion injury

Teduglutide improves liver chemistries in short bowel syndrome-associated intestinal failure: Post hoc analysis.

Chronic hepatic complications are common in patients with short bowel syndrome-associated intestinal failure (SBS-IF). Teduglutide, a glucagon-like peptide-2 analogue, demonstrated efficacy in reducing parenteral nutrition and/or intravenous fluid dependence among patients with SBS-IF in phase 3 clinical studies. This was a post hoc analysis of pooled data from two separate randomized, double-blind, placebo-controlled, multinational phase 3 clinical studies. Adult patients with SBS-IF with parenteral nutrition and/or intravenous fluid dependence without liver disease at baseline were randomized to treatment with the glucagon-like peptide-2 analogue teduglutide (0.05 or 0.10 mg/kg/day) or placebo subcutaneously once daily for 24 weeks. Mixed-effects models assessed the baseline predictors of change in liver chemistries. Between baseline and week 24, teduglutide treatment (n = 109) was associated with least squares mean reductions in aspartate aminotransferase (-7.51 IU/L; P = 0.014), alanine aminotransferase (-12.15 IU/L; P = 0.002), and bilirubin (-5.03 µmol/L [-0.057 mg/dl]; P < 0.001) compared with that of the placebo (n = 59). These values were independent of reductions in parenteral nutrition and/or intravenous fluid dependence. Teduglutide treatment was associated with reductions in liver chemistries by week 24, which is beneficial for patients with SBS-IF beyond improvements in parenteral nutrition and/or intravenous fluid dependence. Future studies should examine how long-term teduglutide might mitigate the risk of liver disease in patients with SBS-IF.

Pharmacokinetics and Tolerability of a Single Dose of Apraglutide, a Novel, Long-Acting, Synthetic glucagon-like peptide-2 Analog With a Unique Pharmacologic Profile, in Individuals With Impaired Renal Function.

Renal impairment is a common complication in patients with short bowel syndrome with intestinal failure (SBS-IF). Glucagon-like peptide-2 analogs, such as apraglutide, have been developed as a treatment option for SBS-IF. This study assessed the potential for apraglutide overexposure in individuals with severely impaired renal function versus healthy volunteers with normal renal function. In this phase 1, open-label, multicenter, nonrandomized, parallel-group study, a single dose of apraglutide 5 mg was administered subcutaneously to individuals with severely impaired renal function (<30 mL/min/1.73 m2) and healthy volunteers with normal renal function (≥90mL/min/1.73 m2). Primary pharmacokinetic endpoints were maximum observed concentration (Cmax) and exposure to apraglutide (area under the curve [AUC] from time 0 to infinity [AUCinf], and AUC from time 0 to the last quantifiable concentration [AUClast]). Each group comprised 8 individuals. Results show that patients with severe renal impairment do not have increased apraglutide exposure. Apraglutide achieved a lower Cmax and AUCinf in individuals with severe renal impairment versus those with normal renal function (Cmax = 36.9 vs 59.5 ng/L; AUCinf = 3100 vs 4470 h · ng/mL, respectively). The respective geometric mean ratios were 0.620 and 0.693 for Cmax and AUCinf, and the upper bound of their 90% confidence intervals were <2, indicating patients with severe renal impairment were not overexposed to apraglutide versus those with normal renal function. Adverse events were mild or moderate in severity. Apraglutide does not require dose reduction for any degree of renal impairment and could be used in a broader patient population of renally impaired patients without dose adjustment.

Principles of management of patients with short bowel syndrome

Short bowel syndrome (SBS) is a rare disease accompanied by the phenomena of malabsorption (impaired absorption of food) and maldigestion (phenomena of creato-, steato-and amilorrhea), as a result of resection of most of the small intestine (usually with a residual part of the intestine less than 200 cm) from – due to various etiological factors. One of the severe complications of this syndrome is the development of intestinal failure, which can be manifested by the occurrence of water, electrolyte and white matter disturbances, hypovitaminosis, and deficiency of micro-and macronutrients. It is possible to suspect the development of intestinal failure if the patient continues to have repeated diarrhea 2–3 months after surgery and a progressive decrease in body weight by 5% or more of the initial weight within a month. Therefore, an important aspect in the treatment of SBS is the correction of electrolyte disturbances and maintenance of nutritional status. However, the severity of the patient’s condition is often determined not only by the course of the disease itself, but also by the long-term use of parenteral nutrition after surgery. Therefore, an important aspect in the management of patients with SBS is the cessation of parenteral nutrition as early as possible and the transition to a physiological nature of food intake. This can be achieved both by choosing certain surgical treatment techniques and by using drug therapy – an analogue of glucagon-like peptide-2 – Teduglutide, which increases the functional ability of enterocytes to absorb. SBS is a significant social problem due to the high mortality rate in childhood and a significant percentage of disability in people of working age, which makes it highly relevant to discuss the management strategy for this category of patients.

Long-term outcomes and adverse effects of teduglutide in patients with short bowel syndrome: Highlighting hyperamylasemia and hyperlipasemia.

Short bowel syndrome is a malabsorptive condition that occurs due to surgical removal or a congenital absence of a significant portion of the small intestine. Patients with short bowel syndrome often rely on parenteral support for extended periods or even their entire lives. Teduglutide, a glucagon-like peptide-2 analog, has shown promising results in reducing dependency on parenteral support in these patients by promoting intestinal adaptation and enhancing nutrient absorption. However, the long-term safety of teduglutide remains a concern, particularly with respect to its potential for the development of hyperamylasemia and hyperlipasemia. This study involved patients who received teduglutide from December 2012 to December 2022 at Boston Medical Center. We evaluated outcomes and adverse events, focusing on hyperamylasemia and hyperlipasemia, through chart review. Thirteen eligible patients were identified who had used teduglutide. Of these, the majority (84.6%) experienced a reduction in parenteral support. A high incidence (72.7%) of nonpathological pancreatic enzyme elevation was observed in patients treated with teduglutide. These elevations were often dose dependent and were not associated with any clinical signs of acute pancreatitis or abnormal imaging findings. This study highlights the need for further investigations into the long-term safety of teduglutide and the importance of closely monitoring amylase and lipase levels in patients undergoing treatment with teduglutide.

Predictive Potential of Biomarkers of Intestinal Barrier Function for Therapeutic Management with Teduglutide in Patients with Short Bowel Syndrome.

The human intestinal tract reacts to extensive resection with spontaneous intestinal adaptation. We analyzed whether gene expression analyses or intestinal permeability (IP) testing could provide biomarkers to describe regulation mechanisms in the intestinal barrier in short bowel syndrome (SBS) patients during adaptive response or treatment with the glucagon-like peptide-2 analog teduglutide. Relevant regions of the GLP-2 receptor gene were sequenced. Gene expression analyses and immunohistochemistry were performed from mucosal biopsies. IP was assessed using a carbohydrate oral ingestion test. The study includes 59 SBS patients and 19 controls. Increases in gene expression with teduglutide were received for sucrase-isomaltase, sodium/glucose cotransporter 1, and calcium/calmodulin serine protein kinase. Mannitol recovery was decreased in SBS but elevated with teduglutide (Δ 40%), showed a positive correlation with remnant small bowel and an inverse correlation with parenteral support. Biomarkers predicting clinical and functional features in human SBS are very limited. Altered specific gene expression was shown for genes involved in nutrient transport but not for genes controlling tight junctions. However, mannitol recovery proved useful in describing the absorptive capacity of the gut during adaptation and treatment with teduglutide.

Adult patients with short bowel syndrome treated with teduglutide: A descriptive cohort study.

Teduglutide is a synthetic glucagon-like peptide-2 analogue approved for the treatment of short bowel syndrome associated with chronic intestinal failure (SBS-IF) in adult patients. Clinical trials have demonstrated its ability to reduce parenteral support (PS) requirement. This study aimed to describe the effect of 18-month treatment with teduglutide, evaluating PS and factors associated with PS volume reduction of ≥20% from baseline and weaning. Two-year clinical outcomes were also assessed. This descriptive cohort study collected data prospectively from adult patients with SBS-IF treated with teduglutide and enrolled in a national registry. Data were collected every 6 months and included demographics, clinical, biochemical, PS regimen, and hospitalizations. Thirty-four patients were included. After 2 years, 74% (n = 25) had a PS volume reduction of ≥20% from baseline, and 26% (n = 9) achieved PS independency. PS volume reduction was significantly associated with longer PS duration, significantly lower basal PS energy intake, and absence of narcotics. PS weaning was significantly associated with fewer infusion days, lower PS volume, longer PS duration, and lower narcotics use at baseline. Alkaline phosphatase was significantly lower in weaned patients after 6 and 18 months of treatment. During the 2-year study duration, patients who had PS volume reduction of ≥20% had significantly fewer yearly hospitalizations and hospital-days. Teduglutide reduces PS volume and promotes weaning in adults with SBS-IF. Lack of narcotics and longer PS duration were associated with PS volume reduction and weaning, and lower baseline PS volume and fewer infusion days were favorable in obtaining enteral autonomy.

The indications and results of the use of teduglutide in patients with short bowel.

Short bowel syndrome (SBS) is a rare condition defined as a reduced residual functional small intestinal length to less than 200 cm often resulting from extensive intestinal resection, and can lead to chronic intestinal failure (CIF). Patients with SBS-CIF are unable to absorb sufficient nutrients or fluids to maintain metabolic homeostasis through oral or enteral intake and require long-term parenteral nutrition and/or fluids and electrolytes. However, complications may arise from both SBS-IF and life-sustaining intravenous support, such as intestinal failure-associated liver disease (IFALD), chronic renal failure, metabolic bone disease and catheter-related complications. An interdisciplinary approach is required to optimize intestinal adaptation and decrease complications. In the last two decades, glucagon-like peptide 2 (GLP-2) analogs have sparked pharmacological interest as a potential disease-modifying therapy for SBS-IF. Teduglutide (TED) is the first developed and marketed GLP-2 analog for SBS-IF. It is approved in the United States, Europe, and Japan for use in adults and children with SBS-IF who are intravenous supplementation dependent. This article discusses the indications, candidacy criteria and results of the use of TED in patients with SBS.

Characterization of the Pharmacokinetic and Pharmacodynamic Profile of Apraglutide, a Glucagon-Like Peptide-2 Analog, in Healthy Volunteers.

Apraglutide (FE 203799) is a glucagon-like peptide-2 (GLP-2) analog under development for the treatment of intestinal failure associated with short bowel syndrome (SBS-IF) and graft-versus-host disease (GvHD). Compared with native GLP-2, apraglutide has slower absorption, reduced clearance, and higher protein binding, enabling once-weekly dosing. This study evaluated the pharmacokinetic (PK) and pharmacodynamic (PD) profile of apraglutide in healthy adults. Healthy volunteers were randomized to receive 6 weekly subcutaneous (s.c.) administrations of 1, 5, or 10 mg apraglutide or placebo. PK and citrulline samples were collected at multiple timepoints. Kinetic parameters of apraglutide and citrulline were calculated using noncompartmental analysis; repeated PD measures were analyzed with a mixed model of covariance A population PK/PD model was developed that also included data from a previous phase I study in healthy volunteers. Twenty-four subjects were randomized; 23 received all study drug administrations. Mean estimated apraglutide clearance was 16.5‒20.7 L/day and mean volume of distribution was 55.4‒105.0 L. A dose-dependent increase in citrulline plasma concentration was observed, with 5-mg and 10-mg doses inducing higher citrulline levels than 1-mg doses and placebo. PK/PD analysis showed that weekly 5-mg apraglutide induced the maximal citrulline response. Increased plasma citrulline levels were sustained for 10‒17 days after the final apraglutide administration. Apraglutide displays predictable dose-dependent PK and PD profiles, with a 5-mg dose showing significant PD effects. Results suggest that apraglutide has early and enduring effects on enterocyte mass and supports the continued development of weekly s.c. apraglutide for SBS-IF and GvHD patient populations Significance Statement Once-weekly, SC apraglutide results in dose-dependent elevations of plasma citrulline (an enterocyte mass PD marker) with parameters suggesting that apraglutide has lasting effects on enterocyte mass and the potential to provide therapeutic benefits. This is the first report of a model relating GLP-2 agonism and its effects in intestinal mucosa, affording not only the ability to predict pharmacologic effects of GLP-2 analogs but also the exploration of optimal dosing regimens for this drug class across populations with different body weights.

Ironwood to buy VectivBio for $1 billion

Ironwood Pharmaceuticals, a health-care firm focused on gastrointestinal disorders, will acquire VectivBio in a $1 billion all-cash deal. VectivBio specializes in developing treatments for rare conditions such as short bowel syndrome with intestinal failure and acute graft-versus-host disease. The Swiss company’s lead asset is a glucagon-like peptide-2 analog; it is in Phase 3 clinical trials and has an expected readout by year-end.

Pathophysiology of gastrointestinal acute graft-versus-host disease and the potential role of glucagon-like peptide 2.

Acute graft-versus-host disease (aGVHD) is a life-threatening complication after allogeneic haematopoietic cell transplantation, with gastrointestinal (GI) tract involvement (GI aGVHD) being one of the leading causes of morbidity and mortality. Whilst systemic steroids are the standard first-line treatment for aGVHD, approximately 50% of patients become steroid refractory (SR), which is associated with poor outcomes. Existing options for SR-GVHD are limited, and there is a significant unmet need for new non-immunosuppressive treatment approaches in patients with GI aGVHD. Here, we review newer concepts in the pathogenesis of GI aGVHD and present the evidence for the role of glucagon-like peptide 2 (GLP-2) in maintaining and protecting GI epithelial cells, including the enterocytes, intestinal stem cells and Paneth cells, which are direct targets of aGVHD. Finally, we discuss the therapeutic rationale for GLP-2 treatment as a tissue regeneration approach and the potential use of the novel GLP-2 analogue apraglutide as an adjunctive treatment for GI aGVHD.

Pharmacokinetics, Safety, and Tolerability of Glepaglutide, a Long-Acting GLP-2 Analog, in Subjects with Renal Impairment.

Glepaglutide is a novel, ready-to-use, long-acting, glucagon-like peptide-2 (GLP-2) analog intended for the treatment of patients with short bowel syndrome (SBS). This study investigated the impact of renal function on the pharmacokinetics and safety of glepaglutide. In this 3-site, non-randomized, open-label study, 16 subjects were enrolled: 4 with severe renal impairment (eGFR 15 to < 30mL/min/1.73m2), 4with end stage renal disease (ESRD) not on dialysis (eGFR < 15mL/min/1.73m2), and 8 matching controls with normal renal function (eGFR ≥ 90mL/min/1.73m2). Blood samples were collected over a 14-day period following a single subcutaneous (SC) dose of glepaglutide 10mg. Safety and tolerability were assessed throughout the study. The primary pharmacokinetic parameters were area under the curve between dosing and 168h (AUC0-168h) and the maximum plasma concentration (Cmax). There was no clinically relevant difference between subjects with severe renal impairment/ESRD and normal renal function with respect to total exposure (AUC0-168h) and peak plasma concentrations (Cmax) of glepaglutide following a single SC dose. A single SC dose of glepaglutide 10mg appeared safe and well tolerated in subjects with normal renal function and subjects with severe renal impairment or ESRD. No serious adverse events were reported, and no safety issues were identified. No difference in glepaglutide pharmacokinetics was seen between renal impaired and normal subjects. Based on this trial, dose adjustment appears not to be warranted in SBS patients with renal impairment. The trial is registered at http://www. gov (NCT04178447) and has the EudraCT number: 2019-001466-15.

Biased GLP-2 agonist with strong G protein-coupling but impaired arrestin recruitment and receptor desensitization enhances intestinal growth in mice.

Glucagon-like peptide-2 (GLP-2) is secreted postprandially by enteroendocrine L-cells and stimulates growth of the gut and bone. One GLP-2 analogue is approved for short bowel syndrome (SBS). To improve therapeutic efficacy, we developed biased GLP-2 receptor (GLP-2R) agonists through N-terminal modifications. Variants with Ala and Trp substitutions of the first seven positions of GLP-2(1-33) were studied in vitro for affinity, G protein activation (cAMP accumulation), recruitment of β-arrestin 1 and 2, and internalization of the human and mouse GLP-2R. The intestinotrophic actions of the most efficacious (cAMP) biased variant were examined in mice. Ala substitutions had more profound effects than Trp substitutions. For both, alterations at positions 1, 3 and 6 most severely impaired activity. β-arrestin recruitment was more affected than cAMP accumulation. Among Ala substitutions, [H1A], [D3A] and [F6A] impaired potency (EC50 ) for cAMP-accumulation >20-fold and efficacy (Emax ) to 48%-87%, and were unable to recruit arrestins. The Trp substitutions, [A2W], [D3W] and [G4W] were partial agonists (Emax of 46%-59%) with 1.7-12-fold decreased potencies in cAMP and diminished β-arrestin recruitment. The biased variants, [F6A], [F6W] and [S7W] induced less GLP-2R internalization compared with GLP-2, which induced internalization in a partly arrestin-independent manner. In mice, [S7W] enhanced gut trophic actions with increased weight of the small intestine, increased villus height and crypt depth compared with GLP-2. G protein-biased GLP-2R agonists with diminished receptor desensitization have superior intestinotrophic effects and may represent improved treatment of intestinal insufficiency including SBS.

The Role of a Colon-in-Continuity in Short Bowel Syndrome.

Short bowel syndrome (SBS) is a rare gastrointestinal condition that is defined as having less than 200 cm of remaining small intestine. SBS results from extensive surgical resection and is associated with a high risk for intestinal failure (IF) with a need for parenteral support (PS). Depending on the region of intestinal resection, three different main anatomy types can be distinguished from each other. In this review, we synthesize the current knowledge on the role of the colon in the setting of SBS-IF with a colon-in-continuity (SBS-IF-CiC), e.g., by enhancing the degree of intestinal adaptation, energy salvage, and the role of the microbiota. In addition, the effect of the disease-modifying treatment with glucagon-like peptide-2 (GLP-2) analogs in SBS-IF-CiC and how it differs from patients without a colon will be discussed. Overall, the findings explained in this review highlight the importance of preservation of the colon in SBS-IF.

Comprehensive physicochemical characterization of a peptide-based medicine: Teduglutide (Revestive®) structural description and stress testing

Teduglutide (Revestive®) is a glucagon-like peptide-2 analogue used for the treatment of short bowel syndrome, a rare life-threatening condition in which the amount of functional gut is too short to enable proper absorption of nutrients and fluids. During handling prior to administration to the patient in hospital, it is possible that peptide-based medicines may be exposed to environmental stress conditions that could affect their quality. It is therefore essential to carry out stress testing studies to evaluate how such medicines respond to these stresses. For this reason, in this paper we present a strategy for a comprehensive analytical characterization of a peptide and a stress testing study in which it was subjected to various stress conditions: heating at 40 °C and 60 °C, light exposure and shaking. Several complementary analytical techniques were used throughout this study: Far UV circular dichroism, intrinsic protein fluorescence spectroscopy, dynamic light scattering, size-exclusion chromatography and intact and peptide mapping reverse-phase chromatography coupled to mass spectrometry. To the best of our knowledge, this is the first study to offer an in-depth description of the chemical structure of teduglutide peptide and its physicochemical characteristics after stress stimuli were applied to the reconstituted medicine Revestive®.

Опыт применения аналога глюкагоноподобного пептида-2 у ребенка с синдромом короткой кишки

This article presents a clinical case of ultra-short bowel syndrome. The development of the underlying disease and comorbid disorders are described in dynamics, difficulties and therapeutic options are discussed. This clinical case reflects the real practice of managing a child with a rare disease using current possibilities of pharmacotherapy. Key words: short bowel syndrome, nutritional status, intestinal adaptation, glucagon-like peptide-2 analog

Glucagon-like peptide-2 analogues for Crohn’s disease patients with short bowel syndrome and intestinal failure

Short bowel syndrome (SBS) with intestinal failure (IF) is a rare but severe complication of Crohn's disease (CD), which is the most frequent benign condition that leads to SBS after repeated surgical resections, even in the era of biologics and small molecules. Glucagon-like peptide-2 analogues have been deeply studied recently for the treatment of SBS-IF. These drugs have a significant intestinotrophic effect and the potential to reduce the chronic dependence of SBS-IF patients on parenteral support or nutrition. Teduglutide has been approved for the treatment of SBS-IF, and apraglutide is currently in clinical development. The use of these drugs was examined with a focus on their use in CD patients.