What is the risk of mortality associated with Semaglutide (Glucagon-like peptide-1 receptor agonist)?

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Last updated: April 15, 2025View editorial policy

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From the Guidelines

Semaglutide is not directly associated with an increased risk of death, and its benefits in managing type 2 diabetes and obesity generally outweigh the risks for most eligible patients. When considering the use of semaglutide, it's essential to weigh the potential benefits against the possible adverse effects, which can include gastrointestinal issues, pancreatitis, and allergic reactions 1. The most recent and highest quality studies, such as the SUSTAIN 6 trial, have demonstrated the cardiovascular benefits of semaglutide, with a reduced risk of cardiovascular death, non-fatal myocardial infarction, or stroke compared to placebo 1.

Key points to consider when prescribing semaglutide include:

  • Starting with a low dose and gradually increasing as tolerated to minimize gastrointestinal side effects
  • Monitoring for signs of pancreatitis, gallbladder problems, and hypoglycemia
  • Regular follow-up appointments to assess the patient's response to the medication and adjust the treatment plan as needed
  • Educating patients on the importance of reporting concerning symptoms to their healthcare provider immediately

The safety profile of semaglutide has been established through extensive clinical trials, including the LEADER trial, which showed a benefit in cardiovascular outcomes with GLP-1 receptor agonists 1. Additionally, a recent randomized double-blind study found that semaglutide reduced the risk of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke in patients with pre-existing cardiovascular disease and a BMI > 27 1.

Overall, the available evidence suggests that semaglutide is a safe and effective treatment option for eligible patients, and its benefits in reducing morbidity and mortality outweigh the potential risks. Therefore, semaglutide should be considered a viable treatment option for patients with type 2 diabetes or obesity, under the guidance of a healthcare provider.

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 The FDA drug label mentions cardiovascular death as part of the major adverse cardiovascular events that semaglutide is intended to reduce the risk of, but it does not provide direct information on semaglutide causing death.

From the Research

Semaglutide Death

  • There is no direct evidence of semaglutide causing death in the provided studies 2, 3, 4, 5, 6.

Adverse Effects of Semaglutide

  • Semaglutide has been associated with adverse effects such as:
    • Gastrointestinal disturbances 2, 3, 5, 6
    • Pancreatic safety concerns, including pancreatitis and pancreatic cancer 2, 4, 6
    • Thyroid cancer 2, 6
    • Gallbladder events 2, 6
    • Cardiovascular aspects 2, 3, 6
    • Acute kidney injury 2, 6
    • Diabetic retinopathy complications 2, 6
    • Injection-site and allergic reactions 2

Safety Profile of Semaglutide

  • The established safety profile for semaglutide is similar to that of other GLP-1RAs 2.
  • Semaglutide has an overall favorable risk/benefit profile for patients with type 2 diabetes 2.
  • However, patients at risk for deterioration of existing diabetic retinopathy should be carefully monitored if treated with semaglutide, particularly if also treated with insulin 2.

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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