International Journal of Clinical Case Reports 2024, Vol.14, No.5, 253-261 http://medscipublisher.com/index.php/ijccr 255 3.2 Major clinical trials for GLP-1 receptor agonists GLP-1 receptor agonists have been extensively studied for their glycemic and cardiovascular benefits. In a network meta-analysis, GLP-1 receptor agonists, such as liraglutide and semaglutide, significantly reduced major adverse cardiovascular events (MACE) in patients with type 2 diabetes, with liraglutide demonstrating reductions in cardiovascular mortality (Roddick and Zheng, 2018). Moreover, the SUSTAIN 9 trial confirmed that semaglutide, when added to SGLT2 inhibitor therapy, provided greater glycemic control and weight loss compared to placebo in patients with poorly controlled diabetes (Zinman et al., 2019). 3.3 Comparative efficacy of novel antidiabetic drugs The comparative efficacy of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors has been explored in multiple meta-analyses. A systematic review of 98 clinical trials revealed that GLP-1 receptor agonists were most effective in reducing composite renal events, while SGLT2 inhibitors provided a lower risk of acute kidney injury compared to both DPP-4 inhibitors and GLP-1 receptor agonists (Yang et al., 2022). Furthermore, a comparative study found that SGLT2 inhibitors were more effective in reducing heart failure hospitalizations, while GLP-1 receptor agonists were superior in reducing stroke risk (Sabouret et al., 2022). 4 Safety and Adverse Effects 4.1 Common side effects of SGLT2 inhibitors SGLT2 inhibitors are associated with several common side effects, primarily due to their mechanism of promoting glucose excretion through urine. One of the most notable adverse effects is an increased risk of urinary tract infections (UTIs) and genital infections, especially in women. These infections occur due to the increased glucose concentration in the urine, which creates an environment conducive to bacterial and fungal growth (Consoli et al., 2018). Another significant risk is diabetic ketoacidosis (DKA), particularly in individuals with type 1 diabetes or those with severe insulin deficiency. SGLT2 inhibitors can also lead to volume depletion and hypotension, especially in older adults or patients on diuretics (Edwards et al., 2022). 4.2 Safety profile of GLP-1 receptor agonists GLP-1 receptor agonists are generally well-tolerated but can lead to gastrointestinal side effects, such as nausea, vomiting, and diarrhea, particularly when treatment is first initiated. These effects tend to be dose-dependent and may subside over time. Another concern is the potential for pancreatitis, although the incidence is relatively low. GLP-1 receptor agonists have also been associated with a low risk of hypoglycemia, particularly when used in combination with insulin or sulfonylureas (Consoli et al., 2018). Cardiovascular safety trials have demonstrated the beneficial effects of GLP-1 receptor agonists on cardiovascular outcomes, adding a favorable aspect to their safety profile (Wright et al., 2022). 4.3 Managing adverse effects in clinical practice Managing the adverse effects of novel antidiabetic therapies involves patient education and regular monitoring. For SGLT2 inhibitors, it is important to advise patients to maintain proper hydration to mitigate the risks of hypotension and volume depletion. Monitoring for signs of infection and educating patients on proper hygiene can help reduce the risk of urinary tract and genital infections. Clinicians should be vigilant about the risk of diabetic ketoacidosis, particularly in patients with type 1 diabetes, and discontinue therapy if ketoacidosis develops (Edwards et al., 2022). For GLP-1 receptor agonists, starting at a low dose and gradually increasing the dose can help minimize gastrointestinal side effects. Regular monitoring for pancreatitis symptoms and avoiding the combination with other medications that increase pancreatitis risk is also recommended. 5 Long-Term Outcomes and Cardiovascular Benefits 5.1 Impact of SGLT2 inhibitors on cardiovascular outcomes SGLT2 inhibitors have demonstrated significant cardiovascular benefits in patients with type 2 diabetes. Clinical trials such as the CANVAS and EMPA-REG OUTCOME trials have shown a reduction in the risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular death. Moreover, these drugs have been particularly effective in reducing hospitalization for heart failure (Zelniker et al.,
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