What are the adverse effects of glucagon-like peptide‑2 (GLP‑2) therapy, specifically teduglutide, in patients with short‑bowel syndrome?

Adverse Effects of GLP-2 (Teduglutide) Therapy

Teduglutide is generally well tolerated with adverse effects primarily localized to the gastrointestinal tract, but requires lifelong surveillance for gastrointestinal malignancy risk, which is the most serious concern. 1, 2

Gastrointestinal Adverse Effects

Polyp Formation and Malignancy Risk (Most Critical)

• Teduglutide enhances growth of colonic polyps and can accelerate gastrointestinal cancer progression due to its growth factor properties. 2, 3
• Colonoscopy must be performed before starting treatment to confirm absence of colorectal polyps or malignancies. 2, 3
• Regular surveillance colonoscopies are mandatory during treatment to monitor for new polyp formation or malignant transformation. 2
• Teduglutide is absolutely contraindicated in patients with active gastrointestinal malignancies. 2
• Patients with history of non-gastrointestinal malignancies (especially within 5 years) should avoid teduglutide. 2
• Postmarketing surveillance has identified colorectal polyps, gastric polyps, and small intestinal polyps (duodenum, ileum, jejunum) as adverse reactions. 4

Intestinal Obstruction and Stenosis

• Intestinal obstruction/stenosis occurred in 8 patients across clinical studies, with onsets ranging from 6 days to 19 months. 4
• Two patients required endoscopic dilation and one required surgical intervention for obstruction. 4
• Colonic stenosis, pancreatic duct stenosis, and small intestinal stenosis have been reported in less than 5% of patients. 4

Common Gastrointestinal Symptoms

• Stoma complications occur in 72% of patients treated with teduglutide. 5
• Nausea and abdominal pain each affect 44% of patients. 5
• Abdominal distention and vomiting each occur in 28% of patients. 5

Hepatobiliary and Pancreatic Adverse Effects

• Cholecystitis occurred in 3 patients in clinical trials, all with prior gallbladder disease history, including one case with gallbladder perforation requiring emergency cholecystectomy. 4
• Acute cholecystitis developed in 4 patients during extension studies, with 3 patients developing new-onset cholelithiasis. 4
• Pancreatic pseudocyst, chronic pancreatitis, and acute pancreatitis have been reported. 4
• One patient experienced cholestasis secondary to obstructed biliary stent. 4

Fluid and Cardiovascular Effects

• Peripheral edema occurs in 10% of patients on teduglutide versus 3% on placebo, representing a 56% incidence in some studies. 4, 5
• Fluid overload occurred in 1% of patients. 4
• Congestive heart failure developed in 2 cases (3%), with one serious event possibly associated with undiagnosed hypothyroidism and/or cardiac dysfunction. 4
• Polyuria affects 33% of patients, reflecting altered fluid handling. 5

Injection Site and Local Reactions

• Injection site reactions occur in 61% of patients. 5
• Injection site pain increases as a function of dose and injected volume. 6

Systemic and Metabolic Effects

• Fatigue affects 33% of patients. 5
• Decreased appetite occurs in 22% of patients. 5
• Dizziness affects 28% of patients. 5
• Cough occurs in 22% of patients. 5
• Dyspnea has been reported in less than 5% of patients. 4

Drug Interactions and Altered Absorption

• Teduglutide increases absorption of concomitant oral medications, requiring dose adjustments for drugs with narrow therapeutic indices. 4
• Altered mental status has been observed in patients taking teduglutide with benzodiazepines. 4
• Monitor patients on oral drugs requiring titration for adverse reactions related to increased absorption. 4

Serious Adverse Events

• Catheter-related sepsis and infections of unknown origin have been reported. 5
• Abdominal pain and stoma obstruction occurred as serious adverse events. 5

Key Clinical Pitfalls

The adverse event profile is generally consistent with the underlying disease (short bowel syndrome), making it challenging to distinguish drug-related effects from disease progression. 7 This requires careful baseline documentation before initiating therapy. 8

Adverse effects localized to the gastrointestinal tract with teduglutide contrast sharply with the predominantly systemic and more frequent adverse effects seen with growth hormone therapy, making teduglutide the preferred intestinal growth factor. 1

Long-term safety remains unknown, and theoretical risks of tumor promotion necessitate indefinite surveillance. 8, 2