What are the side effects of Glucagon-like peptide-1 (GLP-1)?

From the Guidelines

GLP-1 receptor agonists commonly cause gastrointestinal side effects, including nausea, vomiting, diarrhea, and constipation, especially when starting treatment or increasing doses, as reported in the most recent study 1.

Common Side Effects

• Nausea and vomiting
• Diarrhea
• Constipation
• Injection site reactions (redness, swelling)
• Headaches
• Dizziness These effects typically improve over time as the body adjusts to the medication.

Serious Side Effects

• Pancreatitis (severe abdominal pain)
• Gallbladder problems
• Kidney issues
• Allergic reactions Some patients experience significant weight loss, which is beneficial for those with obesity but may be concerning for underweight individuals.

Minimizing Side Effects

To minimize side effects, patients should:

• Start with a low dose and gradually increase it as tolerated
• Take the medication as prescribed
• Stay hydrated
• Eat smaller meals
• Report persistent or severe symptoms to their healthcare provider These side effects occur because GLP-1 agonists slow gastric emptying and affect the central nervous system's appetite regulation centers, which helps with blood sugar control and weight management but can lead to digestive discomfort, as noted in 1 and 1.

Additional Considerations

GLP-1 medications may also cause hypoglycemia (low blood sugar), particularly when used with insulin or sulfonylureas, as mentioned in 1. It is essential to weigh the benefits and risks of GLP-1 receptor agonists, considering the individual patient's health status and medical history, as discussed in 1.

From the FDA Drug Label

In adult glycemic control trials of liraglutide injection, there have been 13 cases of pancreatitis among liraglutide injection-treated patients and 1 case in a comparator (glimepiride) treated patient (2.7 vs. 0. 5 cases per 1,000 patient-years). The following additional adverse reactions have been reported during post-approval use of liraglutide injection. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure Gastrointestinal: Acute pancreatitis, hemorrhagic and necrotizing pancreatitis sometimes resulting in death, ileus General Disorders and Administration Site Conditions: Allergic reactions: rash and pruritus Hepatobiliary: Elevations of liver enzymes, hyperbilirubinemia, cholestasis, cholecystitis, cholelithiasis requiring cholecystectomy, hepatitis Immune system: Angioedema and anaphylactic reactions Metabolism and nutrition: Dehydration resulting from nausea, vomiting and diarrhea Neoplasms: Medullary thyroid carcinoma Nervous system: Dysgeusia, dizziness Pulmonary: Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation Renal and urinary: Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis Skin and subcutaneous tissue: Cutaneous amyloidosis

The side effects of GLP-1 (liraglutide) include:

• Pancreatitis: 2.7 cases per 1,000 patient-years
• Hypoglycemia: increased risk when used with insulin secretagogues or insulin
• Hypersensitivity reactions: anaphylactic reactions and angioedema
• Acute kidney injury: postmarketing reports of acute renal failure and worsening of chronic renal failure
• Acute gallbladder disease: cholelithiasis and cholecystitis
• Pulmonary aspiration: rare postmarketing reports during general anesthesia or deep sedation
• Other side effects: nausea, vomiting, diarrhea, dehydration, dysgeusia, dizziness, cutaneous amyloidosis, and medullary thyroid carcinoma 2, 2, 2

From the Research

GLP-1 Side Effects

• The most common side effects of GLP-1 receptor agonists are gastrointestinal, including nausea and digestive problems 3, 4.
• These side effects are often manageable and decrease over time, but can be a major reason for patients to stop taking the medication 4.
• There is no clear evidence of an increased risk of pancreatitis associated with the use of GLP-1 receptor agonists 5, 6, 7.
• Some studies suggest a potential increased risk of cholelithiasis (gallstones) with the use of GLP-1 receptor agonists 6.
• The risk of pancreatic cancer is not significantly different between GLP-1 receptor agonists and comparator arms 6, 7.
• Real-world studies demonstrate high discontinuation rates of GLP-1RAs (20%-50%) within the first year, often due to side effects or high costs of the medications 4.
• Further research is needed to understand possible real-world associations of GLP-1RAs with eye disease and other rare outcomes 4.

Specific Side Effects

• Gastrointestinal side effects are the most common adverse effects of GLP-1 receptor agonists, particularly at higher doses 3.
• Nausea and digestive problems are common side effects, but are often manageable and decrease over time 4.
• Pancreatitis risk is not significantly increased with the use of GLP-1 receptor agonists, according to some studies 5, 6, 7.
• Cholelithiasis (gallstones) may be a potential side effect of GLP-1 receptor agonists, with some studies suggesting an increased risk 6.

Management of Side Effects

• Managing gastrointestinal side effects is crucial to optimize therapeutic outcomes with GLP-1RAs 3.
• Patients should be closely monitored for side effects, and treatment plans should be adjusted as needed 4.
• Further research is needed to understand the exact drivers of early discontinuation and suboptimal dosing of GLP-1RAs 4.