Teduglutide is a glucagon-like peptide 2 (GLP-2) analog which acts by increasing intestinal absorption of the remnant bowel for children with short bowel syndrome (SBS) dependent on parenteral nutrition. We present a 13-year-old male patient with type 2 SBS (55 cm of jejunum) from necrotizing enterocolitis on full oral feeding from the age of 12 months. Because of faltering growth from the age of 11 despite oral hyperphagia, he started Teduglutide at the standard dose. Eighteen months after Teduglutide start the young boy gained 10 kg in weight and 13 cm in height with a significant reduction in bowel distension. No adverse events were reported during the treatment. Pubertal spurt might be impaired in children with SBS on full oral feeding if the caloric need is not met by the residual intestinal absorption rate. GLP-2 analog might represent an option to sustain pubertal spurt in SBS children on full oral feeding with hyperphagia.

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn\'s disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.

BACKGROUND: Short bowel syndrome with chronic intestinal failure (SBS/CIF) is the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance due to a short bowel. Although SBS/CIF is rare, its clinical management is complex, challenging, expensive, and time-consuming.
OBJECTIVE: This study aimed to analyze a single center\'s experience with SBS/CIF in adult patients treated with home parenteral nutrition (HPN).
METHODS: A retrospective single-center analysis of all 13 consecutive adult patients with SBS/CIF was included in an HPN program between January 1994 and August 2023.
RESULTS: Between 1992 and 2023, 13 patients were included in an HPN program. The primary underlying pathology was acute mesenteric ischemia. The median age of starting HPN was 44 years. Most were subjected to several surgeries of extensive intestinal resection with posterior intestinal reconstruction. Five of the 13 patients died while on HPN with a median duration of 42 months. The causes of death related to HPN were catheter sepsis, endocarditis with cardiac failure, or hepatic failure. One patient died due to underlying pathology: pelvic abscesses and bleeding related to radiotherapy. Eight patients remain alive, with a median time of HPN of 173 months. During the HPN support, the most frequent complications were venous catheter infection and venous territory thrombosis. None of the eight patients alive have hepatic failure. Two patients recently started teduglutide with good tolerance and need a reduction in HPN support. All eight patients have a satisfactory quality of life (parenteral support needs range between five and two nutrition bags per week).  Conclusion: Home parenteral nutrition remains the gold standard of SBS/CIF treatment, although teduglutide may reduce HPN needs and complications and provide a better quality of life. Despite the small number of patients, the results shown in this study are not inferior to those in large-volume centers. The existence of the commitment and interest of professionals involved in SBS/CIF at Centro Hospitalar Universitário de Santo António, Portugal, was a fundamental key to achieving those results. A multidisciplinary healthcare group for HPN support can be essential to ensuring these patients\' survival and quality of life.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract (GIT). Glucagon-like peptide-2 (GLP-2) analogs possess high potential in the treatment of IBD by enhancing intestinal repair and attenuating inflammation. Due to the enzymatic degradation and poor intestinal absorption, GLP-2 analogs are administered parenterally, which leads to poor patient compliance. This work aims to develop IBD-targeted nanoparticles (NPs) for the oral delivery of the GLP-2 analog, Teduglutide (TED). Leveraging the overproduction of Reactive Oxygen Species (ROS) in the IBD environment, ROS-sensitive NPs are developed to target the intestinal epithelium, bypassing the mucus barrier. PEGylation of NPs facilitates mucus transposition, but subsequent PEG removal is crucial for cellular internalization. This de-PEGylation is possible by including a ROS-sensitive thioketal linker within the system. ROS-sensitive NPs are established, with the ability to fully de-PEGylate via ROS-mediated cleavage. Encapsulation of TED into NPs resulted in the absence of absorption in 3D in vitro models, potentially promoting a localized action, and avoiding adverse effects due to systemic absorption. Upon oral administration to colitis-induced mice, ROS-sensitive NPs are located in the colon, displaying healing capacity and reducing inflammation. Cleavable PEGylated NPs demonstrate effective potential in managing IBD symptoms and modulating the disease\'s progression.

UNASSIGNED: SBS is a rare and disabling condition. The standard management is based on diet optimization with parenteral supplementation. In addition, glucagon-like peptide-2 (GLP-2)analogs, have shown promising results as disease-modifying therapies for SBS.
UNASSIGNED: Short bowel syndrome (SBS) is defined as a reduction in functional intestinal length to less than 200 cm, leading to intestinal failure (IF) leading to malnutrition and parenteral support dependency. This review discusses the current management of SBS-CIFpatients, the place of GLP-2 analog treatment in terms of efficacy, safety and availability, and the new perspectives opened by the use of enterohormones.
UNASSIGNED: Clinical trials and real-world experience demonstrated that Teduglutide   reduces dependence on parenteral support and has a place in the management of patients with SBS-CIF.  The use of Teduglutide should be discussed in patients stabilized after resection and its introduction requires the advice of an expert center capable of assessing the benefit-risk ratio. The complex, individualized management of SBS-C IF requires theexpertise of a specialized IF center which a multidisciplinary approach. The arrival of new treatments will call for new therapeutic strategies, and the question of how to introduce and monitor them will represent a new therapeutic challenge.

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 5 years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3 months. 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 > 1 year and 9 treated for > 3 years. 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.

(1) Background: We present the first real-world-data study on teduglutide-treated SBS patients in the Slovak Republic and the first study to enable the comparison of the effects of teduglutide treatment between the adult and pediatric populations. (2) Methods: This was a non-interventional retrospective cohort study of adult and pediatric SBS patients treated with teduglutide. Primary and secondary endpoints were the results of teduglutide use at 12 weeks and 6 months after the initiation of treatment, compared to baseline. (3) Results: Teduglutide treatment led to a statistically significant reduction in the volume of intravenous hydration, HPN caloric intake, HPN and intravenous hydration applications per week and to increased urine output in adult patients. The results in the pediatric population were similar, but not statistically significant. A complete weaning off HPN was achieved in 57.14% of all patients (50.00% of children; 62.50% of adults) after a median of 0.99 years of teduglutide treatment (1.07 and 0.98 years for children and adults, respectively). (4) Conclusions: Teduglutide treatment in SBS patients leads to considerable reduction in or even weaning off PN in both pediatric and adult patients.

BACKGROUND: Short bowel syndrome (SBS) resulting from acute aortic dissection (AAD)-induced visceral malperfusions leads to chronic intestinal failure (CIF), necessitating patients to adopt home parenteral nutrition to prevent malabsorption. Teduglutide (TED), a glucagon-like peptide-2 analog, is a promising pharmacotherapy for intestinal rehabilitation that reduces parenteral support and improves the quality of life. Gastric mucosal necrosis, a rare gastrointestinal disorder, had never been observed as an adverse event relevant to this drug. We report a case of mucosal necrosis in the stomach after TED treatment for SBS-CIF with hepatorenal failure.
METHODS: A 68-year-old Japanese man who underwent massive intestinal resection for AAD experienced malnutrition and diarrhea caused by SBS-CIF. The patient received TED to improve intestinal absorption and entero-hepatic circulation besides controlling infectious diseases. Endoscopy showed mucosal hyperplasia in the stomach and duodenum 1.5 months after TED administration. The patient consented to enteral nutrition via a nasogastric tube because of anorexia. The nutritional status gradually improved after initiating enteral feeding. However, the patient experienced hematemesis 13 days after enteral feeding, and endoscopy revealed acute gastric mucosal necrosis, followed by fatal septic shock.
CONCLUSIONS: For patients with SBS, TED is expected to increase intestinal absorption through epithelial proliferation. When SBS is accompanied by multiple ischemic organ failure, TED therapeutic effects remain unclear as malnutrition-associated infectious diseases are refractory, and many underlying mechanisms can be involved.
CONCLUSIONS: TED administration should be deliberately considered for patients with SBS-CIF and multiple organ failure experiencing uncontrolled systemic infection.

Short bowel syndrome with intestinal failure (SBS-IF) is a rare but devastating medical condition. An absolute loss of bowel length forces the patients into parenteral support dependency and a variety of medical sequelae, resulting in increased morbidity and mortality. Interdisciplinary treatment may include therapy with the effective but expensive intestinotrophic peptide teduglutide.
A time-discrete Markov model was developed to simulate the treatment effect [lifetime costs, quality-adjusted life years (QALYs), and life years (LYs)] of teduglutide plus best supportive care compared with best supportive care alone in patients with SBS-IF.
The health status of the model was structured around the number of days on PS. Clinical data from 3 data sets were used: 1) an Austrian observational study (base case), 2) pooled observational cohort studies, and 3) a prospective study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects. Direct and indirect costs were derived from published sources. QALYs, LYs, and costs were discounted (3% per annum).
Under the base case assumption, teduglutide is associated with costs of 2,296,311 € per patient and 10.78 QALYs (13.74 LYs) over a lifetime horizon. No teduglutide is associated with 1,236,816 € and 2.24 QALYs (8.57 LYs). The incremental cost-utility ratio (ICUR) amounts to 123,945 €. In case of the pooled clinical data set, the ICUR increases to 184,961 €. If clinical data based on the study of teduglutide effectiveness in parenteral nutrition-dependent short bowel syndrome subjects were used, the ICUR increased to 235,612 €.
Teduglutide in treating patients with SBS-IF meets the traditional cost-effectiveness criteria from a European societal perspective. Nevertheless, the varying concentrations of teduglutide efficacy leave a degree of uncertainty in the calculations.

UNASSIGNED: Crohn\'s disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment option for these patients. We investigated clinical outcomes of CD-CIF patients with SBS treated with teduglutide.
UNASSIGNED: Adults with CD-CIF and SBS who received teduglutide were identified at a tertiary care academic center between 2012 and 2023. Data was collected retrospectively. Primary outcome measured was reduction in parenteral support (PS) by ≥20% volume, with PS defined as utilization of parenteral nutrition (PN) or intravenous fluids (IVF). Several secondary outcomes included immunosuppressive medication changes, subjective symptom improvement, and stool output.
UNASSIGNED: We identified 32 patients with CD-CIF and SBS receiving teduglutide. Comparing clinical outcomes before and after teduglutide, 26 of 32 patients achieved the primary outcome of ≥20% PS reduction. A decrease was seen in patients requiring PN + IVF, with corresponding increases in patients requiring PN only and IVF only. Among all 3 groups, a total of 23 patients received PN prior to teduglutide, which decreased to 14 following teduglutide. Weekly PN volume reduced from 7.00 to 3.55 L and weekly frequency decreased from 7.00 to 3.00 instances (P < .01). Reductions in weekly volume and frequency were observed among all patients receiving IVF support (25 vs 15). Secondary outcomes showed improvement in patient reported subjective symptoms (84.4%), stool output (90.6%), patients meeting criteria for diarrhea/high ostomy output (27 vs 14), and use of unique antidiarrheal medications (3.0 vs 2.0).
UNASSIGNED: This retrospective case series demonstrated improved clinical outcomes in patients with CD-CIF and SBS treated with teduglutide resulting in decreased PS requirements, antidiarrheal medications requirement, and stool output without significant effects on immunosuppressive therapy.