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
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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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