Teduglutide is a 33-amino-acid analog of glucagon-like peptide-2 (GLP-2), not of GLP-1. FDA approved it in 2012 as Gattex for short bowel syndrome (SBS) in people who still need parenteral support, later expanding the label to children 1 year and older. The peptide is intestinotrophic: it grows absorptive surface. It does not work through the GLP-1 receptor that drives the obesity drugs.

TL;DR

  • Native GLP-2 is an L-cell peptide. Intact half-life in humans is about 7 minutes because dipeptidyl peptidase-4 (DPP-4) cuts alanine at position 2 (Hartmann et al., 2000).
  • Teduglutide puts glycine in that slot. Mean terminal half-life after a subcutaneous shot is about 1.3 hours in SBS and 2 hours in healthy subjects, with 88% absolute bioavailability (FDA label).
  • STEPS (n=86): 63% on teduglutide versus 30% on placebo hit a 20% or greater cut in weekly PN/IV volume at weeks 20 and 24 (Jeppesen et al., 2012).
  • The same trophic biology is why the label wants colonoscopy and upper endoscopy before treatment and on a schedule after it starts.
  • A research vial marked “GLP-2” is not Gattex. It is also not a weight-loss peptide.

Educational only. Not medical advice, not a protocol, and not a reason to inject a catalog analog.

How is GLP-2 different from GLP-1?

Both peptides come from proglucagon in intestinal L-cells. GLP-1 is the incretin. GLP-2 was the leftover 33-residue fragment with no assigned job.

That changed when Drucker’s group showed that GLP-2, not GLP-1, drove small-bowel epithelial proliferation in mice bearing proglucagon-producing tumors (Drucker et al., 1996). GLP-2 is a gut-growth peptide. GLP-1 is not.

The approved product binds the GLP-2 receptor on enteroendocrine cells, subepithelial myofibroblasts, and enteric neurons. Downstream mediators include IGF-1, nitric oxide, and keratinocyte growth factor (KGF). The label also lists more intestinal and portal blood flow and less gastric acid secretion (FDA label).

For the incretin side of this family, see the GLP-1 receptor agonist guide. For the amino-acid primer, see Peptides 101.

Why does native GLP-2 fail as a drug?

DPP-4 eats it. Hartmann infused synthetic human GLP-2 in healthy volunteers and measured intact peptide versus the metabolite GLP-2(3-33): intact half-life was 7.2 plus or minus 2 minutes, and the truncated fragment lasted about 27 minutes (Hartmann et al., 2000).

Teduglutide is recombinant [Gly2]GLP-2, 3752 daltons, made in E. coli. Swap glycine for alanine at position 2 and DPP-4 loses its preferred cut site. That is the same half-life logic as other analog tricks, just a single residue instead of a fatty acid or PEG.

See the DAC, PEGylation, and lipidation guide for those other clocks. Tmax is 3 to 5 hours, volume of distribution is about blood volume, and clearance is mainly renal, so the labeled dose drops from 0.05 mg/kg to 0.025 mg/kg when eGFR is under 60 (FDA label).

What did STEPS actually measure?

STEPS is the 24-week adult trial the label calls Study 1: 86 people with SBS and intestinal failure, randomized 1:1 to subcutaneous teduglutide 0.05 mg/kg daily or placebo. The responder definition was a 20% or greater cut in weekly parenteral volume at both week 20 and week 24 (Jeppesen et al., 2012).

Source Design Primary finding
Hartmann 2000 IV native GLP-2 in healthy adults Intact t1/2 7.2 min (DPP-4)
FDA label, PK Subcutaneous teduglutide Bioavailability 88%; t1/2 1.3 to 2 h
STEPS / Study 1 24 weeks, n=86, 1:1 Responders 63% (27/43) vs 30% (13/43), p=0.002
STEPS, week 24 volume Same trial Mean weekly PN/IV -4.4 L from 12.9 L vs -2.3 L from 13.2 L
STEPS, days off Same trial 1 or more days/week PN reduction: 54% vs 23%
Study 2 extension Up to 30 months on drug 28 of 30 completers still at 20% reduction; 10 weaned off PN/IV

Mean remaining small intestine in Study 1 was about 77 cm, and 45% had a stoma. This is not a recomp protocol. It is a parenteral-support trial in a rare malabsorptive disease.

A dose-ranging study on the label reported roughly 750 to 1000 mL/day more wet-weight absorption, with taller villi and deeper crypts. Plasma citrulline, a crude mucosal-mass marker, moved with that anatomy. When the peptide stops, absorption can fall, so the label tells clinicians to watch fluid and electrolytes after discontinuation.

What does the trophic signal cost?

If a peptide grows epithelium, the safety conversation starts with neoplasia, not nausea. The Gattex label has no boxed warning, but it does tell adults to get colonoscopy and upper endoscopy with polyp removal within 6 months before starting, again at 1 year, then no less often than every 5 years.

Stop the drug if an intestinal malignancy shows up. Temporarily stop it for intestinal or stomal obstruction. Check bilirubin, alkaline phosphatase, lipase, and amylase every 6 months.

Fluid overload, including heart failure, is the other mechanical problem: better absorption plus unchanged parenteral volume is extra water. The trial also flagged more absorption of concomitant oral drugs, benzodiazepines included. That is a clinical monitoring issue, not a stacking tip.

Common adverse reactions at 10% or more included abdominal pain, nausea, abdominal distension, injection-site reaction, vomiting, fluid overload, and hypersensitivity. Among people with a stoma, stoma complications were 42% versus 14% on placebo (FDA label).

Is a catalog GLP-2 vial the same peptide?

No. Gattex is a recombinant, FDA-reviewed [Gly2]GLP-2 product with measured 88% subcutaneous bioavailability and a reconstitution kit (5 mg lyophilized powder plus 0.5 mL sterile water, use within 3 hours). A research vial labeled “GLP-2” has none of that CMC, none of that endoscopy program, and none of that indication.

It is also the wrong receptor if the search query was weight loss. For oral GLP-1 engineering see SNAC and Rybelsus. For mixing math on a prescribed product, use the reconstitution guide and the calculator, then a licensed provider.

Next-generation GLP-2 analogs are trying to leave daily injections. On September 18, 2026, Zealand said EMA’s CHMP issued a positive opinion for glepaglutide (Zeydovio), a long-acting analog studied twice weekly (Zealand, 2026).

In EASE-1, twice-weekly glepaglutide cut weekly parenteral volume 5.13 L versus 2.85 L on placebo. That is a European committee opinion, not a U.S. approval. Zealand is still running EASE-5 for a U.S. filing.

Bottom line

Teduglutide is the DPP-4-resistant GLP-2 analog that turned L-cell gut-growth biology into an FDA-reviewed SBS drug. STEPS showed fewer parenteral liters, not a GLP-1 effect, and a catalog “GLP-2” vial is not Gattex.

This article is educational and is not medical advice. Peptide use belongs under a licensed clinician.