GLP-2
Evidence: C/DEvidence: AGrade C/D — Applies to native/recombinant (non-sequence-modified) human GLP-2, administered subcutaneously to short-bowel-syndrome patients in Jeppesen et al.'s clinical research program (PMID 11231933, 5-week study; PMID 19590736, 2-year extension). This is genuine human interventional evidence, not merely mechanistic/preclinical, but it is concentrated in one research group's disease-specific (short-bowel syndrome) patient population -- not healthy-volunteer physiology data -- and a dedicated search for independent replication by other research groups did not surface additional native-GLP-2-specific human RCTs. This evidentiary concentration is itself a limitation, despite the evidence being real and disease-relevant rather than absent..
Grade A — Teduglutide (GLP-2 analogue) clinical and regulatory programme.
Teduglutide (Gattex/Revestive) is a sequence-modified GLP-2 analogue (glycine substituted for alanine at position 2, conferring DPP-4 resistance and a ~2-hour vs. ~7-minute half-life extension), not native GLP-2 itself. Its FDA approval (2012) for short bowel syndrome and its supporting Phase III clinical trial evidence are specific to this engineered product and do not transfer to native GLP-2's own evidence grade. Native GLP-2's own standalone human evidence is real but comparatively thin, concentrated in one research group's short-bowel-syndrome infusion program. Teduglutide's own dosing, safety monitoring requirements (including colonoscopy screening for polyps), and regulatory indication are product-specific and must not be presented as native-GLP-2 dosing or safety guidance.
Gastrointestinal / Gut-Hormone Signaling
Evidence Snapshot
What this grade covers
Applies to native/recombinant (non-sequence-modified) human GLP-2, administered subcutaneously to short-bowel-syndrome patients in Jeppesen et al.'s clinical research program (PMID 11231933, 5-week study; PMID 19590736, 2-year extension). This is genuine human interventional evidence, not merely mechanistic/preclinical, but it is concentrated in one research group's disease-specific (short-bowel syndrome) patient population -- not healthy-volunteer physiology data -- and a dedicated search for independent replication by other research groups did not surface additional native-GLP-2-specific human RCTs. This evidentiary concentration is itself a limitation, despite the evidence being real and disease-relevant rather than absent.
Regulatory Context
Native GLP-2 is an endogenous hormone and is not itself an FDA-approved drug product. Teduglutide (Gattex, approved 2012) is a sequence-modified GLP-2 analogue FDA-approved for short bowel syndrome in adult and pediatric (1 year and older) patients dependent on parenteral support; its regulatory status, dosing, and safety-monitoring requirements are specific to that product and do not apply to native GLP-2.
Research Takeaway
GLP-2 (Glucagon-Like Peptide-2) is a 33-amino-acid intestinotrophic hormone co-secreted with GLP-1 from intestinal L-cells, but acts on a distinct receptor and has distinct physiology (intestinal growth/repair) from GLP-1 and its drug-class analogues (Semaglutide, Liraglutide, Tirzepatide, Retatrutide).
Evidence boundary: Identity/physiology statement; the GLP-1-family drugs referenced are not GLP-2 evidence in either direction. Do not use GLP-1-family drug evidence to support any GLP-2 claim merely because both names contain 'GLP.'
See all 3 evidence claims →Quick Summary
GLP-2 (Glucagon-Like Peptide-2) is an intestinotrophic gut hormone, co-released with GLP-1 but acting through its own distinct receptor to support intestinal growth, nutrient absorption, and mucosal repair. Controlled clinical research in short-bowel-syndrome patients shows subcutaneous native GLP-2 improves nutrient absorption and nutritional status, with benefits sustained over 2 years, though this evidence is concentrated in one research program. Native GLP-2's very short half-life led to the development of Teduglutide (Gattex), a sequence-modified, FDA-approved analogue with its own separate, larger clinical evidence base and its own product-specific safety-monitoring requirements.
Mechanism & Research Overview
GLP-2 (Glucagon-Like Peptide-2) is an intestinotrophic gut hormone, co-released with GLP-1 but acting through its own distinct receptor to support intestinal growth, nutrient absorption, and mucosal repair. Controlled clinical research in short-bowel-syndrome patients shows subcutaneous native GLP-2 improves nutrient absorption and nutritional status, with benefits sustained over 2 years, though this evidence is concentrated in one research program. Native GLP-2's very short half-life led to the development of Teduglutide (Gattex), a sequence-modified, FDA-approved analogue with its own separate, larger clinical evidence base and its own product-specific safety-monitoring requirements.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
GLP-2 (Glucagon-Like Peptide-2) is a 33-amino-acid intestinotrophic hormone co-secreted with GLP-1 from intestinal L-cells, but acts on a distinct receptor and has distinct physiology (intestinal growth/repair) from GLP-1 and its drug-class analogues (Semaglutide, Liraglutide, Tirzepatide, Retatrutide).
Does not establish
Evidence boundary: Identity/physiology statement; the GLP-1-family drugs referenced are not GLP-2 evidence in either direction. Do not use GLP-1-family drug evidence to support any GLP-2 claim merely because both names contain 'GLP.'
Sources: Clinical Significance of GLP-2 in Short-Bowel Syndrome
Supported
Subcutaneous administration of native/recombinant GLP-2 improves intestinal nutrient absorption and nutritional status in short-bowel-syndrome patients with impaired postprandial GLP-2 secretion, with benefits sustained over a 2-year extension study.
Does not establish
Evidence boundary: Evidence is concentrated in one research group's short-bowel-syndrome patient population; not established in healthy volunteers, and no independent replication by a separate research group was located in this review. Do not generalize to healthy-volunteer use or to weight-management claims outside the short-bowel-syndrome context.
Sources: Glucagon-Like Peptide 2 Improves Nutrient Absorption and Nutritional Status in Short-Bowel Patients with No Colon; Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2 (GLP-2): Compliance, Safety, and Effects on Quality of Life
Supported
Teduglutide (Gattex), an FDA-approved, sequence-modified GLP-2 analogue, has a substantially larger and higher-grade clinical/regulatory evidence base than native GLP-2 itself. Teduglutide's approval, efficacy data, dosing, and safety monitoring requirements are specific to that product and do not establish native GLP-2's own efficacy, safety, or regulatory status.
Does not establish
Evidence boundary: Never present Teduglutide's colonoscopy-monitoring requirement, dosing, or approval as native-GLP-2 guidance.
Sources: FDA Label / DailyMed Record for GATTEX (Teduglutide)
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Higher-Priority Safety Consideration
The official Gattex label documents a potential for hyperplastic/neoplastic changes, including intestinal polyps observed in clinical trials and postmarketing, requiring colonoscopy monitoring. This is a risk of the APPROVED ANALOGUE PRODUCT specifically and must never be presented as a risk of native GLP-2.Safety Consideration
All verified native-GLP-2 human interventional evidence located in this review comes from the same research group's short-bowel-syndrome program (Jeppesen et al.). No independent replication by a separate research group, and no healthy-volunteer native-GLP-2 interventional study, was identified.Safety Consideration
Native GLP-2's short plasma half-life (~7 minutes vs. Teduglutide's ~2 hours) is the core rationale for the Teduglutide development program and a genuine practical limitation of the native molecule for any standalone therapeutic use.
Research Areas Being Studied
Research areas discussed on this page reflect the Gastrointestinal / Gut-Hormone Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2 (GLP-2): Compliance, Safety, and Effects on Quality of Life (2009):
- Glucagon-Like Peptide 2 Improves Nutrient Absorption and Nutritional Status in Short-Bowel Patients with No Colon (2001):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Short Bowel Patients Treated for Two Years with Glucagon-Like Peptide 2 (GLP-2): Compliance, Safety, and Effects on Quality of Life | 2009 | 11 short-bowel-syndrome patients, 2-year subcutaneous GLP-2 | Sustained 2-year compliance, favorable safety profile, and improved quality-of-life measures. | Very small (n=11), single-arm/open extension design. | |
| Glucagon-Like Peptide 2 Improves Nutrient Absorption and Nutritional Status in Short-Bowel Patients with No Colon | 2001 | short-bowel-syndrome patients with no colon | Subcutaneous native/recombinant human GLP-2 over 5 weeks improved intestinal nutrient absorption and nutritional status in short-bowel-syndrome patients with impaired postprandial GLP-2 secretion. | Disease-population-scoped (short-bowel syndrome); not established in healthy volunteers. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| FDA Label / DailyMed Record for GATTEX (Teduglutide) | 2012 | Teduglutide (Gattex), a 33-amino-acid GLP-2 analogue with a glycine-for-alanine substitution at the N-terminal position 2 conferring DPP-4 resistance, has a mean terminal half-life of ~2 hours (healthy subjects; ~1.3 hours in SBS patients) vs. native GLP-2's ~7-minute half-life. FDA-approved 2012 for adult and pediatric (1 year+) short bowel syndrome patients dependent on parenteral support. Label warnings: potential hyperplastic/neoplastic changes (colorectal, gastric, small-intestinal polyps observed in trials and postmarketing, with an animal carcinogenicity signal) requiring colonoscopy monitoring; cholecystitis/cholelithiasis/pancreatitis; intestinal obstruction; fluid overload/CHF. | Product-specific; does not establish native GLP-2's own efficacy, safety, or dosing. Colonoscopy-monitoring requirement is Teduglutide-specific, never native-GLP-2 guidance. | No source link available |
Review Articles / Secondary Sources
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Clinical Significance of GLP-2 in Short-Bowel Syndrome | 2003 | Review summarizing the antisecretory, transit-modulating, and intestinotrophic effects of native GLP-2 and its potential clinical significance for short-bowel patients. |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published research on endogenous GLP-2 and its FDA-approved analogue, Teduglutide. It does not constitute medical advice, a treatment recommendation, or dosing guidance for any GLP-2-related substance or its analogue drug product.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-08-26.
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