From the Guidelines
GLP-1 analogues are associated with several adverse effects, including gastrointestinal side effects, pancreatitis, gallbladder problems, and injection site reactions, and should be used with caution in patients with a history of gastroparesis or medullary thyroid cancer. The most frequent adverse effects of GLP-1 analogues include nausea, vomiting, diarrhea, and constipation, which are typically mild to moderate and often improve over time 1. To minimize these effects, it's recommended to start with a low dose and gradually increase it over several weeks. For example, with semaglutide (Ozempic), starting at 0.25 mg once weekly for 4 weeks, then increasing to 0.5 mg weekly, and potentially to 1 mg weekly after another 4 weeks if needed. Less common but potentially more serious adverse effects include pancreatitis and gallbladder problems. Patients should be advised to seek immediate medical attention if they experience severe abdominal pain, which could indicate acute pancreatitis 1. There's also a small increased risk of gallstones and cholecystitis. Some patients may experience injection site reactions, such as redness or itching, which are usually mild and transient 1. Hypoglycemia is rare when GLP-1 analogues are used alone but can occur more frequently when combined with sulfonylureas or insulin. Key points to consider when prescribing GLP-1 analogues include:
- Starting with a low dose and gradually increasing it over several weeks to minimize gastrointestinal side effects
- Monitoring for signs of pancreatitis and gallbladder problems
- Advising patients to seek immediate medical attention if they experience severe abdominal pain
- Being cautious when using GLP-1 analogues in patients with a history of gastroparesis or medullary thyroid cancer
- Considering the potential increased risk of diabetic retinopathy complications with semaglutide, particularly in patients with a prior history of proliferative retinopathy 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 symptoms such as nausea, vomiting, diarrhea, and abdominal pain 5, 6, 7, 8
- Increased risk of pancreatitis 5, 7, 8
- Gastroparesis 5
- GI bleeding 5
- Constipation 5, 7
- Upper abdominal pain 7
- Dyspepsia 9
Gastrointestinal Adverse Events
Gastrointestinal adverse events are common with GLP-1 analogues, with differences in safety profiles existing between agents 5, 6, 7. For example:
- Semaglutide has been associated with a higher risk of nausea, diarrhea, vomiting, and constipation 7
- Liraglutide has been associated with a higher risk of abdominal pain, pancreatitis, and GI bleeding 5, 7
- Dulaglutide has been associated with a higher risk of abdominal pain, constipation, and diarrhea 5
- Exenatide has been associated with a lower risk of gastrointestinal adverse events compared to other GLP-1 analogues 5, 6
Mechanism of Gastrointestinal Adverse Events
The mechanism of gastrointestinal adverse events associated with GLP-1 analogues is not fully understood, but may be related to the suppression of gastrin secretion 9. Gastrin plays a role in regulating gastric secretion of acid and enzymes, and contributes to the regulation of gastric motility. The suppression of gastrin secretion by GLP-1 may contribute to the gastrointestinal side effects of GLP-1-derived drugs.