What are the risks and benefits of Semaglutide (Glucagon-like peptide-1 receptor agonist)?

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Last updated: March 5, 2025View editorial policy

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From the Guidelines

Semaglutide is a highly effective medication for weight loss and diabetes management, offering significant benefits in terms of substantial weight loss, improved blood sugar control, and reduced cardiovascular risk, but it also comes with important risks to consider, including common side effects like nausea and vomiting, and more serious risks like pancreatitis and gallbladder problems 1. The medication, available as Ozempic, Wegovy, or Rybelsus, works by mimicking GLP-1 hormones to reduce appetite, slow stomach emptying, and improve insulin sensitivity.

  • Benefits of semaglutide include:
    • Substantial weight loss (typically 10-15% of body weight over time) 1
    • Improved blood sugar control
    • Reduced cardiovascular risk, as shown in the SELECT study, which found that semaglutide reduced the composite incidence of death due to cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke at 39.8 months (hazard ratio, 0.80; 95% CI, 0.72-0.90) 1
    • Potential improvements in fatty liver disease
  • Risks and side effects of semaglutide include:
    • Common side effects like nausea, vomiting, diarrhea, and constipation, which often improve over time 1
    • More serious risks like pancreatitis, gallbladder problems, kidney injury, and rare cases of medullary thyroid cancer (seen only in animal studies)
    • Contraindicated in those with personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia syndrome type 2 To minimize side effects, semaglutide should be started at a low dose (0.25mg weekly for injectable forms) and gradually increased, and patients should maintain adequate hydration and consider anti-nausea medications if needed 1. It is also important to note that the medication requires ongoing use to maintain benefits, as weight regain is common upon discontinuation, as shown in the STEP trials, which found that mean weight regain was 11.6% of lost weight after cessation of semaglutide treatment 1.

From the FDA Drug Label

• to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease

OZEMPIC is contraindicated in patients with: • A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) • Known hypersensitivity to semaglutide or to any of the product components

  1. 1 Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures

  2. 2 Pancreatitis In glycemic control trials, acute pancreatitis was 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).

5.3 Diabetic Retinopathy Complications In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with OZEMPIC (3.0%) compared to placebo (1. 8%).

The risks of Semaglutide include:

  • Thyroid C-cell tumors: increased incidence in mice and rats
  • Pancreatitis: confirmed in 7 OZEMPIC-treated patients
  • Diabetic retinopathy complications: more events occurred in patients treated with OZEMPIC
  • Hypersensitivity reactions: known hypersensitivity to semaglutide or product components
  • Medullary thyroid carcinoma (MTC): personal or family history of MTC or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

The benefits of Semaglutide include:

  • Reduced risk of major adverse cardiovascular events: in adults with type 2 diabetes mellitus and established cardiovascular disease 2
  • Improved glycemic control: stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner 2
  • Weight reduction: semaglutide lowers body weight 2

From the Research

Risks of Semaglutide

  • Acute pancreatitis 3
  • Anesthetic risks like pulmonary aspiration or residual gastric content 3
  • Acute kidney injury 3
  • Acute gallbladder injury 3
  • Nonarteritic anterior ischemic optic neuropathy 3
  • Diabetic retinopathy 3
  • Gastrointestinal side effects, mainly mild-to-moderate and transient nausea 4

Benefits of Semaglutide

  • Improvement in glycemic control 5, 3, 4, 6, 7
  • Weight loss 5, 3, 4, 6, 7
  • Reduction in cardiovascular risks associated with diabetes mellitus 5, 3, 7
  • Potential therapeutic strategy in Alzheimer's disease due to its anti-neuroinflammatory effects 3
  • Potential treatment for polycystic ovary syndrome 3
  • Reduction in HbA1c levels 5, 4
  • Low risk for hypoglycemia when used in patients who have not achieved glycemic goals with metformin and lifestyle interventions 7

Contraindications and Drug Interactions

  • Contraindications: history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and pregnancy 3
  • Drug interactions: metformin, anti-psychotics, and other diabetes treatments 3

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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