Core Viewpoint - The article discusses the safety and side effects of GLP-1 receptor agonists (GLP-1RA) used in the treatment of type 2 diabetes and obesity, highlighting the importance of understanding potential risks associated with these medications [11][15]. Summary by Sections Side Effects of GLP-1RA - Common side effects of GLP-1RA include nausea, diarrhea, vomiting, constipation, abdominal pain, gastroenteritis, and gastroesophageal reflux disease, which tend to alleviate over time [2]. - Serious health issues may arise, such as increased risk of thyroid cancer, pancreatitis, gallstones, acute kidney injury, retinal damage, and increased heart rate [2]. Comparison of Semaglutide and Tirzepatide - Semaglutide shows good safety in diabetes treatment but can cause gastrointestinal issues, with 17% of patients reporting nausea even at low doses (0.5 mg) [3]. - In clinical trials, 12.2% and 6.4% of patients experienced diarrhea and vomiting, respectively, with a 4% discontinuation rate due to side effects [3]. - Approximately 80% of tirzepatide users report at least one side effect, primarily nausea, diarrhea, constipation, or vomiting, similar to semaglutide [5]. - In trials, 33% of patients on the highest dose of tirzepatide reported nausea, compared to 44% for semaglutide, with diarrhea rates at 23% for tirzepatide and 31% for semaglutide [5]. Safety Warnings and Contraindications - GLP-1RA medications carry a black box warning for potential increased risk of thyroid C-cell tumors, advising against use in patients with a history of medullary thyroid carcinoma or related family history [8]. - Patients with type 2 multiple endocrine neoplasia syndrome, severe allergies to GLP-1RA, or those experiencing pancreatitis should avoid these medications [9]. - Caution is advised for individuals with a history of pancreatitis, severe gastrointestinal diseases, children under 18, and patients with uremia [10]. GLP-1RA and Thyroid Cancer Risk - Animal studies suggest a link between GLP-1RA and the development of medullary thyroid carcinoma, but the association with non-medullary thyroid cancer remains controversial [11]. - Overemphasis on unproven thyroid cancer risks may prevent patients from benefiting from GLP-1RA therapy [11]. - The EMA Safety Committee found that existing evidence does not support a causal relationship between GLP-1RA and thyroid cancer, with randomized controlled trials showing lower incidence rates of thyroid cancer among users [15].