International Journal of Clinical Case Reports 2024, Vol.14, No.5, 253-261 http://medscipublisher.com/index.php/ijccr 254 long-term outcomes and reducing the burden of diabetes-related complications. Specifically, this study will focus on assessing the performance of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors, evaluating their impact on glycemic control, weight management, and cardiovascular health. 2 Classification and Mechanisms of Novel Antidiabetic Drugs 2.1 SGLT2 inhibitors: mechanism and clinical benefits Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of antidiabetic drugs that lower blood glucose levels by promoting glucose excretion through the kidneys. They act on the proximal tubules of the kidney, blocking glucose reabsorption and increasing urinary glucose excretion. This mechanism is independent of insulin, which makes SGLT2 inhibitors useful at any stage of type 2 diabetes management, particularly for patients with insulin resistance or β-cell dysfunction. Clinical benefits of SGLT2 inhibitors include improved glycemic control, weight reduction, and lowered blood pressure. Furthermore, SGLT2 inhibitors have demonstrated cardiovascular benefits, particularly in reducing the risk of hospitalization for heart failure and cardiovascular mortality (Xie et al., 2020). These drugs are also associated with renoprotective effects, showing a reduced risk of adverse kidney outcomes, such as end-stage kidney disease (DeFronzo, 2017; Xie et al., 2020). 2.2 GLP-1 receptor agonists: Mechanism and clinical benefits Glucagon-like peptide-1 (GLP-1) receptor agonists mimic the action of the endogenous incretin hormone GLP-1, which enhances insulin secretion, suppresses glucagon release, slows gastric emptying, and promotes satiety. These effects contribute to improved glycemic control and significant weight loss. GLP-1 receptor agonists are also associated with a lower risk of hypoglycemia due to their glucose-dependent mechanism of action. Additionally, recent studies have highlighted the cardiovascular benefits of GLP-1 receptor agonists, particularly in reducing the risk of stroke and cardiovascular events in patients with type 2 diabetes. They have shown significant reductions in major adverse cardiovascular events (MACE), making them a favorable option for patients with both diabetes and cardiovascular disease (Tomlinson et al., 2016; DeFronzo, 2017). 2.3 DPP-4 inhibitors and other emerging therapies Dipeptidyl peptidase-4 (DPP-4) inhibitors work by inhibiting the enzyme DPP-4, which breaks down incretin hormones such as GLP-1. By preventing the degradation of GLP-1, DPP-4 inhibitors prolong the action of endogenous incretin hormones, thereby increasing insulin secretion and decreasing glucagon levels in a glucose-dependent manner. DPP-4 inhibitors are generally well-tolerated, with a low risk of hypoglycemia and neutral effects on weight. However, unlike SGLT2 inhibitors and GLP-1 receptor agonists, DPP-4 inhibitors have not consistently shown cardiovascular or renal benefits, making them a less preferred option for patients at high cardiovascular risk. Emerging therapies, including dual and triple agonists targeting both incretin and other metabolic pathways, are under investigation to provide more comprehensive metabolic control. These novel agents aim to further improve glycemic control and reduce the risks of complications associated with type 2 diabetes (Luo, 2024). 3 Clinical Trials and Efficacy Data 3.1 Major clinical trials for SGLT2 inhibitors Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been evaluated in several major clinical trials demonstrating their efficacy in glycemic control and cardiovascular outcomes. In a network meta-analysis comparing SGLT2 inhibitors with other antidiabetic drugs, it was found that these inhibitors significantly reduced myocardial infarction (RR 0.86) compared to control, with notable benefits for patients at high cardiovascular risk. Additionally, the combination of SGLT2 inhibitors and GLP-1 receptor agonists was shown to significantly reduce fasting plasma glucose and glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes, while also providing a reduction in body weight and systolic blood pressure (Guo et al., 2019). Another trial highlighted the protective effects of SGLT2 inhibitors in reducing renal outcomes and the risk of kidney disease progression (Cao et al., 2022).
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