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GLP-1 Receptor Agonists Linked to Serious Side Effects and Regulatory Scrutiny

• A recent death in the UK has been linked to tirzepatide (Mounjaro), raising concerns about the safety of GLP-1 receptor agonists. • Online pharmacies selling weight-loss medications face increased regulatory scrutiny due to breaches in safety standards. • Clinical trials show GLP-1 drugs like Wegovy reduce cardiovascular events, but side effects and individual risks must be considered. • Experts caution against viewing GLP-1 drugs as a "silver bullet" for obesity, emphasizing the need for careful patient selection and monitoring.

The death of Susan McGowan in the UK has brought increased scrutiny to the safety and regulation of glucagon-like peptide-1 (GLP-1) receptor agonists, such as tirzepatide (Mounjaro), semaglutide (Ozempic, Wegovy), and others. McGowan's death certificate listed multiple organ failure, septic shock, and pancreatitis, with "the use of prescribed tirzepatide" as a contributing factor. This marks the first known death in the UK linked to this class of drugs. GLP-1 receptor agonists mimic the action of the naturally occurring gut hormone GLP-1, slowing digestion, reducing cravings, and promoting feelings of fullness.

Rising Concerns and Hospitalizations

Concerns about the drugs have been growing, particularly regarding patients obtaining them privately through online pharmacies. The Society for Acute Medicine reported an increase in patients presenting with serious side effects after purchasing GLP-1 receptor agonists online. These complications include inflammation of the pancreas and alterations in blood salt levels. One A&E doctor reported treating a young, non-overweight patient who developed starvation ketoacidosis after taking Wegovy obtained online. Data indicates that between April 2023 and August 2024, 16 patients were treated in A&E departments in NHS Greater Glasgow and Clyde and NHS Lanarkshire due to side effects from GLP-1 drugs. As of May 2024, the MHRA reported 46 hospitalizations and over 5,000 gastrointestinal reactions related to these medications.

Regulatory Response and Online Pharmacy Oversight

The General Pharmaceutical Council is increasing its regulatory focus on online pharmacies, where the market has more than doubled since the pandemic. A previous analysis found that 22% of online pharmacies breached at least one regulatory standard during inspections, compared to 2.6% of traditional pharmacies. This heightened scrutiny comes as the UK plans to expand the use of Mounjaro on the NHS, with a trial targeting 250,000 patients to assess its impact on weight-related conditions and return-to-work outcomes.

Clinical Trial Evidence and Cardiovascular Benefits

Despite the risks, clinical trials have demonstrated significant health benefits beyond weight loss. The SELECT trial, involving 17,600 participants without diabetes, found that Wegovy led to an average weight loss of 10%, compared to 1.5% with placebo. More notably, Wegovy was associated with a 20% reduction in heart attacks, strokes, and cardiovascular deaths, even in patients who did not lose weight. While side effects were more common with Wegovy (17% vs. 8% with placebo), they were mostly mild, including nausea, diarrhea, vomiting, and constipation. Rates of acute pancreatitis were not elevated, and gallbladder disorders were only slightly higher (2.8% vs 2.3%).

Balancing Risks and Benefits

While a paper published in the Lancet cautioned against viewing GLP-1 drugs as a "silver bullet," it acknowledged that without intervention, two-thirds of adults in the US will be obese by 2050. Obesity contributes to various health issues, including diabetes, cancers, heart disease, and kidney disease. The potential benefits of GLP-1 drugs for population health are substantial, but tragedies like McGowan's death underscore the need for careful regulation, patient selection, and monitoring to mitigate individual risks.
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Reference News

[1]
Ozempic, Wegovy, Mounjaro: How dangerous are they? - The Herald
heraldscotland.com · Nov 16, 2024

Susan McGowan's death, linked to the drug Mounjaro, marks the first UK fatality associated with GLP-1 receptor agonists....

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