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Factors associated with early GLP-1 discontinuation. The figure shows... | Download Scientific Diagram

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In comparison to sitagliptin, semaglutide has been shown to significantly reduce the 12-month risk of cognitive deficits, dementia, and epilepsy.[63] In PCOS, a meta-analysis indicated that exenatide and liraglutide exhibit stronger effects on insulin sensitivity and BMI reduction than metformin.[71] A 24-week study found that exenatide led to a significantly higher rate of spontaneous pregnancies and more regular menstrual cycles compared to metformin.[72] Although rapid weight loss in some contexts is associated with an increased risk of frailty fractures, GLP-1RAs may mitigate this effect.[73, 74] Both exenatide and dulaglutide were found to increase bone mineral density, while lixisenatide and liraglutide were associated with a reduced risk of fractures, suggesting differential effects of GLP-1RAs on bone metabolism.[74] OTHER CONSIDERATIONS Side effects and adverse events related to GLP1-RAs While GLP-1RAs are credited with a growing list of health benefits, they have also been associated with a wide variety of adverse effects that may vary among agents.[6, 21] Common side effects include nausea, vomiting, diarrhea, mild tachycardia, and injection site reactions.[75] A pooled analysis of 33 clinical trials (n=13,548) found an increased risk of treatment discontinuation due to gastrointestinal effects such as nausea and vomiting.[6] Potential adverse events include pancreatitis, cholelithiasis, and dehydration.[76] Rodent studies and one observational study in humans have raised concerns about GLP-1RA’s impact on thyroid cancer risk