Can Liraglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist) cause diabetic ketoacidosis, lactic acidosis, pancreatitis, peripheral edema, or vitamin K deficiency?

Liraglutide and Associated Adverse Effects

Liraglutide can cause pancreatitis but does not cause diabetic ketoacidosis, lactic acidosis, peripheral edema, or vitamin K deficiency based on current evidence. 1

Pancreatitis Risk

Liraglutide has been associated with pancreatitis in both clinical trials and post-marketing surveillance:

• The American Gastroenterological Association and American Diabetes Association guidelines acknowledge that pancreatitis has been reported in clinical trials with liraglutide, though causality has not been definitively established 1
• According to the 2023-2024 Diabetes Care Standards, pancreatitis is listed as a possible safety concern for liraglutide 1
• Case reports have documented liraglutide-associated acute pancreatitis, with symptoms typically developing within weeks to months of initiation or dose increase 2, 3, 4

Risk factors for liraglutide-induced pancreatitis:

• History of pancreatitis
• Cholelithiasis
• Alcohol abuse
• Higher doses (≥1.8 mg daily) 5

Management recommendations:

• Discontinue liraglutide immediately if pancreatitis is suspected
• Monitor for symptoms such as severe abdominal pain, nausea, and vomiting
• Check serum amylase and lipase if pancreatitis is suspected

Gallbladder Disease Risk

Liraglutide may increase the risk of cholelithiasis (gallstones) and gallstone-related complications:

• The FDA has reported cases of symptomatic gallstones requiring hospitalization in <0.05% of patients taking liraglutide 3.0 mg 1
• This risk should be considered when prescribing liraglutide, especially in patients with existing gallbladder disease

Other Adverse Effects NOT Associated with Liraglutide

Diabetic Ketoacidosis (DKA)

• No evidence in guidelines or clinical studies suggests liraglutide causes DKA
• In fact, GLP-1 receptor agonists like liraglutide reduce hyperglycemia and may help prevent DKA

Lactic Acidosis

• No association between liraglutide and lactic acidosis has been documented in guidelines or clinical studies
• Lactic acidosis is more commonly associated with metformin, not GLP-1 receptor agonists

Peripheral Edema

• Peripheral edema is not listed as an adverse effect of liraglutide in any of the major guidelines 1
• No evidence supports an association between liraglutide and peripheral edema

Vitamin K Deficiency

• While orlistat (a lipase inhibitor) is associated with potential malabsorption of fat-soluble vitamins including vitamin K 1, there is no evidence that liraglutide causes vitamin K deficiency
• Liraglutide works through a completely different mechanism than orlistat and does not interfere with fat absorption

Common Side Effects of Liraglutide

The most common adverse effects of liraglutide are gastrointestinal:

• Nausea (40% vs 14.8% with placebo) 1
• Vomiting (16% vs 4.3% with placebo) 1
• Diarrhea
• Esophageal reflux
• Injection site reactions
• Elevated heart rate 1

Clinical Implications

When prescribing liraglutide:

1. Screen for risk factors for pancreatitis before initiating therapy
2. Use gradual dose titration to minimize gastrointestinal side effects
3. Monitor for symptoms of pancreatitis and discontinue if suspected
4. Be aware of the risk of gallbladder disease
5. Educate patients about common gastrointestinal side effects and when to seek medical attention

While liraglutide has important benefits for weight loss and glycemic control, clinicians should remain vigilant about the risk of pancreatitis, which though uncommon, represents the most serious potential adverse effect associated with this medication.