Teduglutide: what it is, how it works and what studies have found

Teduglutide is one of the clearest examples of rational peptide design: take a natural gut hormone with a very short life in the circulation, change one amino acid to block the enzyme that inactivates it, and the result is a drug. Unlike many peptides discussed online, it has a full regulatory record, including two phase 3 programmes in adults, a paediatric phase 3 trial, long-term extension data and approved labelling on both sides of the Atlantic.

This overview covers its structure, receptor biology, pharmacokinetics, pivotal trials, reported safety findings and how it is handled in the laboratory. It reports published findings and labelling; it is not a guide to clinical use.

What is teduglutide?

Teduglutide is a 33-amino-acid analogue of human glucagon-like peptide-2 (GLP-2) [1]. The European orphan designation describes the substance as “[Gly2]-recombinant human glucagon-like peptide”, that is, GLP-2 with glycine at position 2 [2]. It was developed under the code ALX-0600 and described as “a dipeptidyl peptidase IV resistant glucagon-like peptide 2 analogue” [3].

GLP-2 itself was identified as an intestinal growth factor in 1996, when nude mice carrying proglucagon-producing tumours showed marked proliferation of the small intestinal epithelium; the responsible factor was GLP-2, “a 33-aa peptide with no previously ascribed biological function” [4]. Teduglutide is approved for short bowel syndrome in patients who depend on parenteral support [1].

Teduglutide structure, sequence and molecular weight

Property	Value
INN	Teduglutide [1]
Development code	ALX-0600 [3]
CAS number	197922-42-2 [5]
Sequence	HGDGSFSDEMNTILDNLAARDFINWLIQTKITD [1]
Length	33 amino acids, linear [1]
Modification versus GLP-2	Ala2 to Gly2 [2]
Molecular formula	C164H252N44O55S [5]
Molecular weight	3752 Da [1] (3752.1 g/mol [5])
Manufacture of approved drug substance	Recombinant DNA technology in Escherichia coli [1]
Drug substance appearance	Clear, colourless to light-straw-coloured liquid [1]
Approved dosage form	White lyophilized powder in single-dose vials, formulated with mannitol, L-histidine and sodium phosphate buffer as excipients and no preservative [1]

The sequence carries a single methionine (Met10) and a single tryptophan (Trp25), with no cysteines and no lipid or polymer modification. Teduglutide is therefore a short-acting peptide; its improvement over GLP-2 comes from protease resistance rather than albumin binding.

Mechanism of action: the GLP-2 receptor

The GLP-2 receptor was cloned in 1999. It is a G protein-coupled receptor “closely related to the glucagon and GLP-1 receptors”, expressed in the gut, and the human gene maps to chromosome 17p13.3 [6]. Cells expressing it responded to GLP-2, but not to GLP-1 or related peptides, with increased cAMP (EC50 0.58 nM) and showed high-affinity binding (Kd 0.57 nM) [6]. GLP-2 analogues that activated the receptor in vitro were intestinotrophic in vivo [6].

The US label describes the mechanism as follows [1]:

• GLP-2 is secreted by L-cells of the distal intestine and is known to increase intestinal and portal blood flow and inhibit gastric acid secretion.
• Teduglutide binds GLP-2 receptors on intestinal subpopulations of enteroendocrine cells, subepithelial myofibroblasts and enteric neurons of the submucosal and myenteric plexus.
• Receptor activation releases local mediators including insulin-like growth factor-1 (IGF-1), nitric oxide and keratinocyte growth factor (KGF).

The label does not list the absorptive enterocyte among these cell types, and it attributes the effect to locally released mediators, so the trophic action on the mucosa is described as indirect [1].

Structural and functional effects in patients match this biology. In the 2005 phase 2 study, 21 days of teduglutide in patients with an end jejunostomy increased villus height by 38%, crypt depth by 22% and mitotic index by 115% compared with baseline [3]. Across the pivotal trials, teduglutide increased plasma citrulline, a biomarker of enterocyte mass [7] [8].

Why glycine at position 2

Native GLP-2 is a substrate of dipeptidyl peptidase-4 (DPP-4). Teduglutide’s Gly2 substitution makes it DPP-4 resistant, and in animal models it “prolongs the intestinotrophic properties of GLP-2” [3].

Teduglutide half-life and pharmacokinetics

Parameter	Value (US label)
Absolute bioavailability (subcutaneous, healthy subjects)	88% [1]
Time to peak concentration	3 to 5 hours [1]
Volume of distribution	103 mL/kg, similar to blood volume [1]
Clearance	About 123 mL/hr/kg, similar to GFR; primarily renal [1]
Terminal half-life, healthy adults	About 2 hours [1]
Terminal half-life, short bowel syndrome	About 1.3 hours [1]
Terminal half-life, children 1 to 11 years	0.7 ± 0.2 hours [1]
Accumulation on repeated dosing	None observed [1]
Metabolism	Not studied in humans; expected degradation to small peptides and amino acids, as for endogenous GLP-2 [1]

Exposure rises with renal impairment, consistent with kidney clearance [1].

Development history and timeline

Year	Event	Ref
1996	GLP-2 identified as an intestinal epithelial growth factor in mice	[4]
1999	Human and rat GLP-2 receptors cloned	[6]
2001	EU orphan designation granted for [Gly2]GLP-2 in short bowel syndrome	[2]
2005	Phase 2 results for ALX-0600 published	[3]
2011	First 24-week phase 3 trial published; authors had consulted for NPS Pharmaceuticals and Nycomed	[7]
2012	STEPS phase 3 results published (ClinicalTrials.gov lists Shire as sponsor, Nycomed as collaborator)	[8] [9]
30 August 2012	EU marketing authorisation	[2]
21 December 2012	FDA approval, NDA 203441 (new molecular entity)	[10]
2016 to 2020	STEPS-2 and STEPS-3 extension data and paediatric phase 3 published	[11] [12] [13]
8 January 2026	EU authorises the first teduglutide generic, Teduglutide Viatris	[14]

The NDA holder listed on Drugs@FDA today is Takeda [10].

Teduglutide clinical trials: key studies and findings

Study	Phase / design	Population	n	Duration	Primary endpoint	Main finding	Ref
Jeppesen 2005	Phase 2, open-label, metabolic balance	SBS with end jejunostomy or colon in continuity	16 (per protocol)	21 days	Intestinal absorption	Wet weight absorption +743 g/day (pooled); villus height +38% (end jejunostomy)	[3]
Jeppesen 2011	Phase 3, randomised, placebo-controlled, two dose groups	SBS with intestinal failure	83	24 weeks	Graded response score	Lower-dose group significant (16/35, p = 0.007); higher-dose group not (8/32 vs 1/16, p = 0.16)	[7]
STEPS	Phase 3, randomised, placebo-controlled	SBS with intestinal failure	86	24 weeks	Responders: >20% reduction in parenteral support at weeks 20 and 24	63% vs 30% (P = .002)	[8]
STEPS-2	Open-label extension	STEPS completers and eligible untreated patients	88	Up to 2 years	Long-term safety and efficacy	13 patients reached full enteral autonomy	[11]
STEPS-3	Open-label extension	STEPS-2 completers	14	1 year	Long-term safety and efficacy	2 more patients reached independence from parenteral support	[12]
Paediatric phase 3	Randomised, double-blind across two dose groups, plus standard-care arm	Children with SBS and intestinal failure	59	24 weeks	≥20% reduction in parenteral support at week 24	54.2% and 69.2% vs 11.1% with standard care (P < 0.05)	[13]

Phase 2 (2005)

Sixteen patients with short bowel syndrome completed the per-protocol analysis. Pooled across groups, teduglutide increased absolute wet weight absorption by 743 g/day and relative absorption by 22%, increased urine weight and sodium excretion, and reduced faecal wet weight and faecal energy excretion (all versus baseline) [3]. The effects reversed after the drug-free follow-up period [3]. The most common side effects were enlargement of the stoma nipple and mild lower leg oedema [3].

The first phase 3 trial (2011)

In 83 patients randomised to one of two teduglutide dose groups or placebo for 24 weeks, the higher-dose group did not reach statistical significance on the graded response score (8/32 versus 1/16 on placebo, p = 0.16), while the lower-dose group did (16/35, p = 0.007) [7]. The authors suggested that a higher baseline parenteral volume in the higher-dose group may explain the discrepancy, since absolute volume reductions were equal [7]. Three treated patients were completely weaned off parenteral support, and villus height, plasma citrulline and lean body mass increased compared with placebo [7].

STEPS

STEPS (NCT00798967) randomised 86 patients with short bowel syndrome and intestinal failure to teduglutide or placebo for 24 weeks [8] [9]. Responders, defined as a reduction of more than 20% in parenteral support volume at weeks 20 and 24, were 27/43 (63%) with teduglutide and 13/43 (30%) with placebo (P = .002) [8]. At week 24, mean parenteral support volume fell by 4.4 L/week with teduglutide versus 2.3 L/week with placebo (P < .001) [8]. A reduction of at least one day per week of parenteral support occurred in 54% versus 23% (P = .005) [8]. Treatment-emergent adverse events leading to discontinuation were similar (2 versus 3 patients) [8].

STEPS-2 and STEPS-3

STEPS-2 enrolled 88 patients for up to two years of open-label teduglutide; 65 (74%) completed it [11]. Among completers, clinical response was achieved in 28/30 (93%) of patients treated since the start of STEPS, and mean parenteral support volume fell by 7.6 L/week (66%) in that group [11]. Thirteen patients achieved full enteral autonomy [11]. STEPS-3 followed 14 of these patients for a further year; 13 completed it, two more achieved independence from parenteral support, and no patient had a treatment-related serious adverse event [12].

Children

The paediatric phase 3 study randomised 59 children to two blinded teduglutide dose groups or a non-blinded standard-of-care arm for 24 weeks; all 59 completed it [13]. A reduction of at least 20% in parenteral support at week 24 was achieved by 54.2% and 69.2% in the two teduglutide groups versus 11.1% with standard care (P < 0.05 versus standard care), and five children (two and three in the respective teduglutide groups) achieved enteral autonomy [13]. The most common treatment-emergent adverse events were pyrexia and vomiting [13].

Safety findings reported in studies and labelling

The US label lists five warnings and precautions [1]:

Warning	Basis in the label
Acceleration of neoplastic growth	Pharmacological activity and tumour findings in rat and mouse carcinogenicity studies; potential to cause hyperplastic changes including neoplasia
Gastrointestinal polyps	Intestinal polyps identified in clinical studies; postmarketing colorectal, gastric and small intestinal polyps reported
Intestinal obstruction	Intestinal or stomal obstruction; treatment interrupted pending clinical evaluation
Biliary and pancreatic disease	Periodic monitoring of bilirubin, alkaline phosphatase, lipase and amylase recommended
Fluid overload, including congestive heart failure	Parenteral support adjusted and continued treatment reassessed if it occurs

The label also notes potential for increased absorption of concomitant oral medicines [1]. In two 24-week placebo-controlled adult studies (136 patients), adverse reactions reported more often than with placebo included abdominal pain (30% versus 22%), nausea (23% versus 20%), upper respiratory tract infection (21% versus 12%) and abdominal distension (20% versus 2%) [1]. In STEPS-2, the most common treatment-emergent adverse events were abdominal pain (34%), catheter sepsis (28%) and decreased weight (25%) [11].

Teduglutide regulatory status by region

Region	Status	Ref
United States	Approved 21 December 2012 (NDA 203441); indicated for adults and children 1 year and older with SBS who are dependent on parenteral support	[1] [10]
European Union	Authorised since 30 August 2012; orphan designation EU/3/01/077 (2001). Generic Teduglutide Viatris authorised 8 January 2026, indicated from 4 months corrected gestational age	[2] [14]
Other regions	Not reviewed here; check the national regulator

Teduglutide in laboratory research

Teduglutide is used as a reference GLP-2 receptor agonist and as a tool for studying intestinal adaptation:

• Receptor pharmacology: cAMP accumulation and radioligand binding in cells expressing the cloned GLP-2 receptor [6].
• Intestinotrophic models: small bowel weight, villus height and crypt cell proliferation in mice, the readouts used to discover GLP-2’s function [4].
• Human biomarkers: villus height, crypt depth and mitotic index in mucosal biopsies [3], and plasma citrulline as a marker of mucosal mass [8].
• Analytical characterisation: reversed-phase HPLC for purity and related substances, LC-MS for identity against the 3752 Da target [1], and peptide mapping to confirm the Gly2 substitution and the full 33-residue sequence.

Synthesis, purity and impurities

The approved drug substance is produced in a recombinant Escherichia coli strain [1]. For research-scale material, a 33-residue peptide without disulfides or lipidation is within the normal range of Fmoc solid-phase synthesis followed by preparative HPLC; the choice between chemical and other routes is discussed in SPPS vs LPPS.

Sequence features that matter for the impurity profile:

• Position 2. The defining Gly2 residue must be confirmed; an Ala2 variant would be native GLP-2, which is DPP-4 sensitive [3].
• Methionine 10 and tryptophan 25. Both are oxidation-prone residues, so oxidised variants are expected related substances.
• Five aspartates and three asparagines. These are sites for isomerisation, aspartimide formation and deamidation.
• Recombinant-specific impurities. Material made in E. coli also needs control of host-cell proteins and DNA, which do not arise in chemical synthesis.

Degradation and process impurity classes are summarised in peptide API impurities and specifications.

Storage and stability of lyophilized teduglutide

The approved product is a lyophilized powder formulated with mannitol, L-histidine and sodium phosphate buffer [1]. The label specifies refrigerated storage at 2 °C to 8 °C before dispensing, with no freezing, and allows storage at up to 25 °C after dispensing with a 90-day use-by date [1]. For research material, which is usually supplied without excipients, frozen storage in a sealed, desiccated container is the conservative default. General guidance is in lyophilised peptide stability and storage, and cycle design for formulated products is covered in the peptide lyophilization guide.

Teduglutide vs related peptides

	Native GLP-2	Teduglutide
Length	33 amino acids [4]	33 amino acids [1]
Position 2	Alanine	Glycine [2]
DPP-4	Susceptible	Resistant [3]
Receptor	GLP-2 receptor [6]	GLP-2 receptor [1]
Source	L-cells of the distal intestine [1]	Recombinant E. coli (approved product) [1]
Duration of action	Limited by DPP-4 cleavage; intestinotrophic effect shorter in animal models [3]	Terminal half-life about 2 h healthy, 1.3 h SBS [1]

GLP-2 is a proglucagon-derived peptide and its receptor is closely related to the glucagon and GLP-1 receptors [6], but cells expressing the GLP-2 receptor did not respond to GLP-1 [6]. Teduglutide therefore sits in a different pharmacological class from the GLP-1 receptor agonists used in metabolic disease, despite the shared design principle of DPP-4 protection.

How Winhycare Pharma supplies teduglutide

Winhycare Pharma supplies teduglutide as research-use-only material, at a purity of at least 99% as stated in our brochure, with a certificate of analysis covering identity, purity and peptide content. Custom synthesis is available. Product details are on the teduglutide page; to discuss supply, contact our pharma team.

For laboratory research use only. Not for human or veterinary use.