Glepaglutide: Side Effects
Known side effects, contraindications, and interactions
📌TL;DR
- •6 known side effects documented
- •5 mild, 1 moderate, 0 severe
- •4 contraindications listed
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Side Effects Severity Chart
Reported in approximately 72% of patients in the phase 2 trial. Includes stoma prolapse, high output, and peristomal complications. Related to the intestinotrophic effects of GLP-2 receptor activation in patients with ostomies.
Reported in approximately 61% of patients. Includes erythema, induration, and pain at the injection site. Generally grade 1-2 and self-limiting.
Reported in approximately 56% of patients. Related to fluid retention from increased intestinal absorption. May be managed by adjusting parenteral support volumes.
Reported in approximately 44% of patients. A GLP-2 class effect related to slowed gastric emptying. Usually mild and self-limiting.
Reported in approximately 44% of patients. Related to intestinal adaptation and increased mucosal growth. May decrease with continued treatment.
Reported in approximately 33% of patients. May be related to fluid shifts during intestinal adaptation or the underlying SBS condition.
⛔Contraindications
- •Active intestinal obstruction or severe intestinal stricture
- •Known or suspected intestinal malignancy (GLP-2 promotes intestinal cell proliferation)
- •Known hypersensitivity to glepaglutide or any excipient
- •Active inflammatory bowel disease with severe intestinal inflammation (relative contraindication)
⚠️Drug Interactions
- •No formal drug interaction studies have been completed. However, as glepaglutide increases intestinal absorption, oral drug bioavailability may increase, potentially requiring dose adjustments for medications with narrow therapeutic indices.
- •Parenteral support volumes must be adjusted as intestinal absorption improves to avoid fluid overload.
Community-Reported Side Effects
See which side effects community members report most frequently.
Based on 10+ community reports
View community protocolsSafety Overview#
Glepaglutide has been evaluated in phase 1 healthy volunteer studies, the phase 2 trial (18 patients), and the phase 3 EASE SBS 1 trial (106 patients). The safety profile is consistent with the GLP-2 analog class and the SBS patient population. The phase 3 trial confirmed that glepaglutide was safe and well tolerated. No new safety signals were identified compared to known GLP-2 class effects.
Gastrointestinal Adverse Events#
As a GLP-2 analog that promotes intestinal growth and alters GI motility, gastrointestinal adverse events are the most prominent safety finding:
Stoma Complications#
- Frequency: ~72% in phase 2 data
- Manifestations: High stoma output, peristomal skin irritation, stoma prolapse
- Mechanism: GLP-2-driven intestinal mucosal growth and increased secretory function
- Management: Stoma care optimization; may require PS adjustment
Nausea and Vomiting#
- Nausea: ~44% of patients
- Vomiting: ~28% of patients
- Mechanism: GLP-2-mediated slowing of gastric emptying
- Temporal pattern: Often more pronounced early in treatment
Abdominal Pain and Distention#
- Abdominal pain: ~44% of patients
- Abdominal distention: ~28% of patients
- Mechanism: Related to intestinal adaptation, increased mucosal mass, and altered motility
- Usually self-limiting as adaptation stabilizes
Injection Site Reactions#
- Frequency: ~61% of patients
- Severity: Generally grade 1-2 (mild to moderate)
- Manifestations: Erythema, induration, pain at the injection site
- Management: Site rotation between abdomen and thigh
Fluid-Related Effects#
Peripheral Edema#
- Frequency: ~56% of patients
- Mechanism: Increased intestinal fluid absorption combined with continued parenteral support at pre-treatment volumes
- Management: Timely reduction of PS volume as intestinal absorption improves
- Clinical significance: Underscores the importance of careful PS adjustment during glepaglutide treatment
Serious Adverse Events#
In the phase 2 trial, serious adverse events were reported in 4 patients:
- Abdominal pain (n=1)
- Stoma obstruction (n=1)
- Catheter-related sepsis (n=1)
- Infection of unknown origin (n=1)
No deaths occurred in the trial. In the phase 3 trial, glepaglutide was assessed to be safe and well tolerated without new safety signals.
Adverse Event Summary#
| Adverse Event | Frequency | Severity | Notes |
|---|---|---|---|
| Stoma complications | ~72% | Moderate | GLP-2 class effect |
| Injection site reactions | ~61% | Mild | Grade 1-2; site rotation recommended |
| Peripheral edema | ~56% | Mild | Adjust PS volumes |
| Nausea | ~44% | Mild | GLP-2 class effect |
| Abdominal pain | ~44% | Mild | Related to adaptation |
| Fatigue | ~33% | Mild | May improve over time |
| Abdominal distention | ~28% | Mild | Related to adaptation |
| Vomiting | ~28% | Mild | GLP-2 class effect |
GLP-2 Class Safety Concerns#
Intestinal Polyps and Neoplasm Risk#
All GLP-2 analogs carry a theoretical risk of promoting growth of intestinal polyps or neoplasms because GLP-2 stimulates intestinal crypt cell proliferation. Teduglutide carries a boxed warning regarding this risk, and colonoscopy surveillance is recommended. While no polyp signal has been specifically reported with glepaglutide, the same monitoring approach is warranted for any GLP-2 agonist.
Biliary and Pancreatic Effects#
GLP-2 receptors are expressed in the gallbladder and pancreas. Gallbladder-related events (cholecystitis, cholelithiasis) have been reported with teduglutide and should be monitored with any GLP-2 analog.
Contraindications#
- Intestinal obstruction: GLP-2-driven intestinal growth could worsen obstruction
- Intestinal malignancy: Known or suspected malignancy contraindicates intestinal growth stimulation
- Hypersensitivity: To glepaglutide or any excipient
Drug Interactions#
No formal drug-drug interaction studies have been completed for glepaglutide. Key considerations:
- Increased oral drug absorption: As intestinal absorptive surface increases, oral drug bioavailability may rise
- Narrow therapeutic index drugs: May require dose monitoring (e.g., warfarin, digoxin, phenytoin, cyclosporine)
- Parenteral support: Must be adjusted to avoid fluid overload as intestinal absorption improves
Related Reading#
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Frequently Asked Questions About Glepaglutide
What are the most common side effects of glepaglutide?
The most commonly reported side effects in clinical trials include stoma complications (72%), injection site reactions (61%), peripheral edema (56%), nausea and abdominal pain (44% each), and fatigue (33%). Most adverse events are mild to moderate and related to the expected pharmacological effects of GLP-2 receptor activation.
Who should not use glepaglutide?
Glepaglutide should be avoided in patients with active intestinal obstruction, known or suspected intestinal malignancy, or hypersensitivity to the drug. Caution is warranted in patients with severe inflammatory bowel disease. As an investigational drug, use is restricted to clinical trials.
Does glepaglutide interact with other medications?
No formal drug interaction studies have been completed. However, as glepaglutide increases intestinal absorption, the bioavailability of oral medications may increase. This is particularly relevant for drugs with narrow therapeutic indices that may require dose monitoring.
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Medical Disclaimer
This website is for educational and informational purposes only. The information provided is not intended to diagnose, treat, cure, or prevent any disease. Always consult with a qualified healthcare professional before using any peptide or supplement.