International Journal of Clinical Case Reports 2024, Vol.14, No.5, 253-261 http://medscipublisher.com/index.php/ijccr 256 2019). The benefits appear to be independent of glucose control, with mechanisms likely related to hemodynamic effects, such as reducing blood pressure and promoting diuresis (Kim et al., 2021). SGLT2 inhibitors have also shown renoprotective effects, slowing the progression of chronic kidney disease in patients with diabetes (Scheen, 2018). 5.2 Cardiovascular and renal benefits of GLP-1 receptor agonists GLP-1 receptor agonists have also shown significant cardiovascular benefits, primarily in reducing MACE, particularly in patients with established atherosclerotic cardiovascular disease. The LEADER and SUSTAIN trials demonstrated the ability of GLP-1 receptor agonists, such as liraglutide and semaglutide, to reduce the risk of cardiovascular death and stroke (Song et al., 2024). GLP-1 receptor agonists exert their benefits through anti-atherogenic and anti-inflammatory mechanisms, independent of their glucose-lowering effects. In addition to cardiovascular protection, these drugs have shown modest renoprotective effects, particularly in reducing the progression of albuminuria (Ahuja and Chou, 2016; Salmen et al., 2023b). 5.3 Long-term efficacy and safety in diabetic patients The long-term efficacy and safety of SGLT2 inhibitors and GLP-1 receptor agonists have been widely supported by cardiovascular outcomes trials (CVOTs). Both classes of drugs offer complementary benefits: SGLT2 inhibitors are more effective in preventing heart failure and renal outcomes, while GLP-1 receptor agonists have a more pronounced effect on reducing atherosclerotic events. When combined, these therapies provide additional protection, as evidenced in recent real-world studies, which show that their combination reduces cardiovascular risks more effectively than either agent alone (Azoulay et al., 2023). Despite these benefits, long-term safety considerations, such as the increased risk of urinary tract infections with SGLT2 inhibitors and gastrointestinal issues with GLP-1 receptor agonists, should be managed carefully in clinical practice (Edwards et al., 2022). 6 Comparative Effectiveness of Novel Antidiabetic Drugs 6.1 Comparison of SGLT2 inhibitors and GLP-1 receptor agonists SGLT2 inhibitors and GLP-1 receptor agonists have demonstrated efficacy in both glycemic control and cardiovascular benefits. A 2021 meta-analysis comparing these two drug classes found that SGLT2 inhibitors were more effective at reducing the risk of hospitalization for heart failure, while GLP-1 receptor agonists were superior in reducing the risk of non-fatal stroke (Palmer et al., 2021). Both classes significantly reduced all-cause mortality, but SGLT2 inhibitors provided more pronounced renal protection, particularly in patients with chronic kidney disease, whereas GLP-1 receptor agonists had a stronger effect on lowering non-fatal cardiovascular events such as myocardial infarction and stroke (Wright et al., 2022). 6.2 Combined use of novel antidiabetic drugs The combination of SGLT2 inhibitors and GLP-1 receptor agonists has shown significant clinical promise. Studies indicate that the combination therapy leads to greater reductions in HbA1c, body weight, and blood pressure compared to either drug used alone (Díaz-Trastoy et al., 2020). Real-world data also suggest that this combination therapy is associated with a decreased risk of major adverse cardiovascular events (MACE) and hospitalization for heart failure, providing additional cardiovascular benefits beyond what either drug achieves independently (Azoulay et al., 2023). Additionally, a systematic review highlighted that the combination therapy resulted in better renal outcomes, with reduced progression of albuminuria and estimated glomerular filtration rate (GFR) decline (Guo et al., 2020). 6.3 Patient-centric considerations in drug selection The choice between SGLT2 inhibitors and GLP-1 receptor agonists, or their combination, should be driven by individual patient profiles. For patients at higher risk of heart failure or chronic kidney disease, SGLT2 inhibitors may be preferred due to their stronger protective effects in these areas. Conversely, for patients with a history of stroke or atherosclerotic cardiovascular disease, GLP-1 receptor agonists may offer more benefit. Combination therapy should be considered in patients who fail to achieve adequate glycemic control with monotherapy and
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