Table 1.

Main studies and case reports on glucagon-like peptide-2 analogues in Crohn’s disease with short bowel syndrome

Ref.	Molecule tested	Number of patients	Number of CD patients	Study type	Main results	Adverse events
Jeppesen et al[64], 2005	Teduglutide	16	12 (in clinical remission)	Pilot open label, phase II	Increased wet weight absorption; decreased urine weight and urine sodium excretion; decreased fecal wet weight and fecal energy content; increased villus height, crypt depth and mitotic index in end-jejunostomy patients	Enlargement of the stoma nipple; mild lower leg oedema; severe AE (dehydration, sepsis, CS) in 4/16, not judged to be related to the drug
Jeppesen et al[65], 2012	Teduglutide	43 (+ 43 PBO)	10 (in clinical remission)	Multicenter, randomized, double blind, PBO-controlled phase III	63% of TED patients had a ≥ 20% reduction of PS volume at week 24 (significant versus 30% of the PBO group); increased serum citrulline (index of intestinal mucosa mass)	Mostly mild GI symptoms (abdominal pain, nausea, stoma complication, or abdominal distension); 7/43 CS; not different from PBO
Schwartz et al[66], 2016	Teduglutide	88	16	2 yr open label extension study	Clinical response (≥ 20% reduction of PS volume) in 28/30 (93%) and 66% of PS volume reduction in TED/TED group; 13 reached enteral autonomy	34%abdominal pain; 25% episodes of weight decrease; 39% infections (SAE); 2 CD exacerbations (12% of CD, SAE)
Kochar et al[89], 2017	Teduglutide	13	13 (8 on biologics and/or IS)	Retrospective cohort study (median duration 1 yr)	9 patients on PN at the beginning of therapy; 1 patient still on PN at the end of therapy; PS reduced from median 9000 mL/wk to 3100 mL/wk, 6 patients no PS at the end	Among non-immunosuppressed (5) only 2 minor AE and 1 CS; among immunosuppressed (8) minor AE, 3 CS and 2 pancreatitis
Barberio et al[94], 2019	Teduglutide	1	1 (on EN and adalimumab)	Case report	EN reduction of 50% after 24 wk of TED; EN suspension after 72 wk of treatment	Transient nausea and mild abdominal pain and nausea
Al Draiweesh et al[90], 2019	Teduglutide	2	2 (on biologics)	Case report	Weaning off from PS after 7 mo of TED; improvement in oral intake, reduced stool output, and weight gain; reduction of PN to 1 night/wk	Any reported
Naimi et al[84], 2019	Glepaglutide	16	8	Double-blind randomised phase II trial	1 mg daily glepaglutide reduces the fecal output by 592 mg/d; 10 mg daily glepaglutide reduces the fecal output by 833 mg/d	Stoma complications (73%); injection site reactions (61%); peripheral edema (56%); nausea and abdominal pain (44%); SAEs (stoma obstruction, sepsis) in 4 patients
Joly et al[74], 2020	Teduglutide	54	16	Retrospective multicenter real life cohort	85% of patients were responders (PS reduction ≥ 20%) at week 24; 24% weaned off PS at week 24	Not specifically collected
Borghini et al[91], 2020	Teduglutide	1	1 (clinically active)	Case report	At least 20% reduction in PS; daily Kcal intake reduction of 15%; reduction in CD activity and severity	Two mild CVC-related infections
Mouillot et al[93], 2020	Teduglutide	1	1	Case report	Reduction of PS and increase of nutrients absorption; hypertrophy of villi at capsule endoscopy; increase in the size of intestinal villi and crypts assessed by biopsy	Not specifically assessed
Puello et al[75], 2021	Teduglutide	18	10	Retrospective single center real life cohort	Response (reduction of > 20% PS) in: 16 (75%) patients at 12 mo; 10 of 13 (76.9%) patients at 24 mo; 7 of 10 (70%) patients at 36 mo; 3 of 3 (100%) patients at 60 mo; 5 patients (all CD) weaned off PS	Abdominal pain or cramping (3); volume overload (1); taste loss (1); legs edema (2); increase in ostomy size (2)
Eliasson et al[82], 2022	Apraglutide	8	3 (in clinical remission)	Open label phase I-II trial	Weekly 5 mg apraglutide increases urinary output by 714 mL/d; weekly 10 mg apraglutide increases urinary output by 795 mL/d	Polyuria (7/8); any stoma complication (6/8); thirst decrease (4/8) and appetite decrease (3/8); edema (4/8); no SAE related to the drug

CD: Crohn’s disease; PN: Parenteral nutrition; PS: Parenteral support; EN: Enteral nutrition; TED: Teduglutide; PBO: Placebo; GI: Gastrointestinal; SAEs: Severe adverse events; CS: Catheter-related sepsis; CVC: Central venous catheter; IS: Immunosuppressives; AE: Adverse events.