What condition is a 25-year-old woman with type 2 diabetes mellitus, hypertension, generalized anxiety disorder, and obesity at increased risk of when taking liraglutide (Victoza) for weight loss?

Liraglutide Increases Risk of Pancreatitis

Liraglutide therapy increases this patient's risk of pancreatitis, which is a well-documented adverse effect of GLP-1 receptor agonists that requires immediate discontinuation if suspected. 1, 2

Evidence from FDA Labeling and Guidelines

The FDA drug label explicitly warns that "acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide injection" based on spontaneous postmarketing reports. 2 In glycemic control trials, there were 13 cases of pancreatitis among liraglutide-treated patients versus 1 case in comparator groups (2.7 vs. 0.5 cases per 1,000 patient-years), with nine classified as acute pancreatitis and four as chronic pancreatitis. 2

The 2022 AGA Clinical Practice Guideline on obesity pharmacotherapy confirms this risk, reporting that among approximately 29,277 patients who took liraglutide 3.0 mg between 2015 and 2018, there were 40 cases of acute pancreatitis (<0.1%) requiring hospitalization. 1

Clinical Presentation and Monitoring

Patients must be observed carefully for persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting. 2 If pancreatitis is suspected, liraglutide should be promptly discontinued and appropriate management initiated. 2 If pancreatitis is confirmed, liraglutide should not be restarted. 2

The 2023 obesity guidelines from South and Southeast Asia specifically list pancreatitis as a contraindication and caution for liraglutide use, recommending monitoring for signs and symptoms of pancreatitis. 1

Risk Factors in This Patient

This 25-year-old patient has central obesity with a BMI of 35.7, which is a known risk factor for pancreatitis. 3 The FDA label notes that some patients who developed pancreatitis had other risk factors such as cholelithiasis. 2 The 2023 ADA Standards of Care emphasize using caution in patients with cholelithiasis and monitoring for acute gallbladder disease. 1

Why Not the Other Options

Bladder cancer is not associated with liraglutide; this concern is specific to pioglitazone. 1

Peripheral edema is not a recognized adverse effect of GLP-1 receptor agonists like liraglutide. 1

Urinary tract infections are not listed as adverse effects in any guideline or the FDA label for liraglutide. 2

Vitamin K deficiency is associated with orlistat (a lipase inhibitor that causes malabsorption of fat-soluble vitamins A, D, E, and K), not with liraglutide. 1

Additional Safety Concerns

While pancreatitis is the correct answer, clinicians should also be aware that liraglutide carries additional risks including:

• Acute gallbladder disease and cholelithiasis: The AGA guideline reported 17 cases of symptomatic gallstones (<0.05%) requiring hospitalization. 1
• Thyroid C-cell tumors: Black box warning for risk of medullary thyroid carcinoma, contraindicated in patients with personal or family history of MTC or MEN 2. 2, 1
• Acute kidney injury: Can occur secondary to severe nausea, vomiting, diarrhea, and dehydration. 2
• Hypoglycemia: Increased risk when combined with insulin secretagogues or insulin, though this patient is only on metformin. 2

Practical Implementation

The 2022 AGA guideline recommends gradual dose titration to minimize gastrointestinal adverse effects: start with 0.6 mg daily for 7 days, then increase by 0.6 mg weekly (1.2 mg, 1.8 mg, 2.4 mg) until reaching the maintenance dose of 3.0 mg after 4 weeks. 1 This titration strategy may help reduce the risk of severe gastrointestinal complications that could precipitate pancreatitis. 1