From the Guidelines
GLP-1 analogues are associated with several adverse effects, including gastrointestinal side effects, increased risk of pancreatitis, and potential thyroid C-cell tumors, and should be used with caution in patients with a history of gastroparesis or medullary thyroid carcinoma. The most common adverse effects of GLP-1 analogues are nausea, vomiting, and diarrhea, which are usually most pronounced at the start of treatment and often improve over time 1. To minimize these effects, it's recommended to start with a low dose and gradually increase, such as starting semaglutide at 0.25 mg weekly and increasing to 0.5 mg after 4 weeks, and potentially to 1 mg after another 4 weeks if needed and tolerated. Other common adverse effects include:
- Headache
- Dizziness
- Injection site reactions
- Loss of appetite, which can contribute to weight loss but may be problematic in certain populations More serious but less common side effects include:
- Increased risk of pancreatitis, with patients requiring monitoring for symptoms such as severe abdominal pain 1
- Potential thyroid C-cell tumors, observed in rodents but not conclusively in humans
- Increased risk of diabetic retinopathy complications, particularly with semaglutide, predominantly in patients with a prior history of proliferative retinopathy 1 The adverse effect profile of GLP-1 analogues should be carefully considered in patients with a history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, and these medications should be used with caution in patients with a history of gastroparesis or pancreatitis. Additionally, patients should be monitored for symptoms of hypoglycemia, particularly when used in combination with sulfonylureas or insulin, and dose adjustments of these medications may be necessary when starting a GLP-1 analogue 1.
From the FDA Drug Label
The following serious adverse reactions are described below or elsewhere in the prescribing information: • Risk of Thyroid C-cell Tumors • Pancreatitis • Diabetic Retinopathy Complications • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin • Acute Kidney Injury • Hypersensitivity Most common (≥ 5%) and occurring more frequently than placebo in clinical trials: nausea, hypoglycemia, vomiting, diarrhea, feeling jittery, dizziness, headache, dyspepsia, constipation, asthenia.
The adverse effects of GlP-1 analogues include:
- Pancreatitis: post-marketing reports of acute pancreatitis, sometimes fatal, have been reported with exenatide, liraglutide, and semaglutide 2, 3, 4
- Hypoglycemia: increased risk of hypoglycemia when used in combination with insulin secretagogues or insulin, especially with liraglutide and semaglutide 3, 4
- Acute Kidney Injury: post-marketing reports of acute kidney injury and worsening of chronic renal failure have been reported with exenatide, liraglutide, and semaglutide 2, 3, 4
- Hypersensitivity: serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with exenatide, liraglutide, and semaglutide 2, 3, 4
- Gastrointestinal symptoms: nausea, vomiting, diarrhea, dyspepsia, and constipation are common adverse reactions reported with GLP-1 analogues 2, 3, 4
From the Research
Adverse Effects of GLP-1 Analogues
The use of Glucagon-like peptide-1 (GLP-1) analogues has been associated with several adverse effects, including:
- Gastrointestinal adverse events such as abdominal pain, constipation, diarrhea, nausea, and vomiting 5, 6, 7, 8
- Increased risk of pancreatitis 5, 7, 8
- Gastroesophageal reflux disease, gastritis, bezoar, breath odor, intra-abdominal hematoma 7
- Acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea 8
- Injection site reactions, headache, and nasopharyngitis 8
Comparison of Adverse Effects among Different GLP-1 Analogues
Studies have shown that different GLP-1 analogues have varying rates of adverse effects, including:
- Dulaglutide and liraglutide had higher rates of abdominal pain, constipation, diarrhea, and nausea and vomiting than semaglutide and exenatide 5
- Liraglutide and exenatide had the highest rates of pancreatitis 5
- Semaglutide had the greatest risk of nausea, diarrhea, vomiting, constipation, and pancreatitis 7
- Liraglutide had the greatest risk of upper abdominal pain and pancreatitis 7
Management of Gastrointestinal Side Effects
Guidelines for managing gastrointestinal side effects of GLP-1 receptor agonists in obesity have been recommended, including: