What are the main side effects of Semaglutide (Glucagon-like peptide-1 (GLP-1) receptor agonist)?

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Last updated: March 29, 2025View editorial policy

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From the Guidelines

Semaglutide can cause several notable side effects, including nausea, vomiting, diarrhea, and decreased appetite, which are the most common adverse effects, as reported in the most recent study 1.

Common Side Effects

The most common side effects of semaglutide include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
  • Constipation These side effects typically occur during the initial weeks of treatment and often improve over time 1.

Serious Side Effects

More serious but less common side effects include:

  • Pancreatitis (inflammation of the pancreas)
  • Gallbladder problems
  • Hypoglycemia (especially when used with insulin or sulfonylureas)
  • Increased heart rate
  • Kidney problems
  • Allergic reactions There have also been concerns about a potential increased risk of thyroid C-cell tumors based on animal studies, though this hasn't been confirmed in humans 1.

Minimizing Side Effects

To minimize side effects, doctors typically start patients on a low dose and gradually increase it, allowing the body to adjust to the medication over time 1.

Special Considerations

Semaglutide may also cause injection site reactions when administered subcutaneously, and patients with a history of pancreatitis or cholelithiasis should use caution when taking this medication 1.

Monitoring and Contraindications

Patients should be monitored for suicidal ideation and behavior, and semaglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or MEN2, as well as in pregnant or breastfeeding women 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 [see Warnings and Precautions (5. 1)] • Pancreatitis [see Warnings and Precautions (5.2)] • Diabetic Retinopathy Complications [see Warnings and Precautions (5.3)] • Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin [see Warnings and Precautions (5.5)] • Acute Kidney Injury [see Warnings and Precautions (5.6)] • Hypersensitivity [see Warnings and Precautions (5.7)]

The main side effects of Semaglutide are:

  • Pancreatitis: confirmed by adjudication in 7 OZEMPIC-treated patients (0.3 cases per 100 patient years) versus 3 in comparator-treated patients (0.2 cases per 100 patient years) 2
  • Diabetic Retinopathy Complications: more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC (3.0%) compared to placebo (1.8%) 2
  • Hypoglycemia: increased when OZEMPIC is used in combination with insulin secretagogues or insulin 2
  • Acute Kidney Injury: postmarketing reports of acute kidney injury and worsening of chronic renal failure in patients treated with GLP-1 receptor agonists 2
  • Hypersensitivity: serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with GLP-1 receptor agonists 2

From the Research

Main Side Effects of Semaglutide

The main side effects of Semaglutide, a Glucagon-like peptide-1 (GLP-1) receptor agonist, are:

  • Gastrointestinal effects, such as nausea and diarrhea, which are the most frequently reported adverse events 3, 4, 5
  • Increased incidence of gastrointestinal adverse events, including vomiting 4
  • Risk of hypoglycemia is low, but can occur, especially when used in combination with other glucose-lowering therapies 3, 5
  • Increased incidence of pancreatitis, although cases are infrequent 4
  • Potential increased risk of diabetic retinopathy, although the odds ratio is not significantly elevated 4

Common Adverse Events

Common adverse events associated with Semaglutide include:

  • Nausea
  • Diarrhea
  • Vomiting
  • Decreased appetite
  • Abdominal pain
  • Injection site reactions (for subcutaneous Semaglutide) 3, 4, 5

Cardiovascular Safety

Semaglutide has been shown to have a cardiovascular safety profile similar to that of subcutaneous Semaglutide, with no increased risk of major adverse cardiovascular events (MACE) 3, 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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