Cardiovascular Diseases Unit Department of Internal Medicine, Le Scotte Hospital Siena, University of Siena, Viale Bracci, 53100, Siena, Italy.
Metabolic Diseases Unit, Department of Internal Medicine, University of Siena, Siena, Italy.
Heart Fail Rev. 2018 May;23(3):325-335. doi: 10.1007/s10741-018-9669-0.
Heart failure (HF) is a common complication in patients with type 2 diabetes and it is closely associated with high morbidity and mortality rate. The incidence of cardiovascular events in patients with diabetes is related to high levels of glycemia, expressed by increase of HbA1c levels. However, there is little evidence to indicate that glycemic control can reduce the incidence of HF events in this population. Recently, several new antidiabetic drugs have been proposed although the exact clinical impact on heart failure occurrence and deterioration is under debate. Most common oral antidiabetic medication such as SGLT2, GLP-1 receptor agonist, metformin, and DPP4 inhibitor revealed peculiar metabolic and biomolecular signal effects. Moreover, the negative effects of thiazolidinediones on HF prognosis, on cardiac function, and exercise tolerance is of great interest. Conversely, several studies on GLP-1RA have highlighted many positive effects on cardiac myocytes, reducing apoptosis through cAMP/PKA/CRCB-mediated pathways protecting against oxidative stress. DPP-4 inhibitors have a controversial effect: saxagliptin and alogliptin may increase the risk of HF as opposed to vildagliptin and sitagliptin. Metformin increases myocardial ATP levels due to activation of 5-AMPK and this could explain the positive link between the drug and events rate reduction in diabetic patients with HF. The more interesting class of new drugs is SGLT2 inhibitors, that seems to have a positive effect on cardiac function by 38% reduction of HF incidence and mortality with empagliflozin treatment. In this review, we would analyze the specific effects of each class so as to better elucidate the clinical impact of antidiabetic drug on HF for guiding the clinicians in the choice of a best individualized therapy.
心力衰竭（HF）是 2 型糖尿病患者的常见并发症，与高发病率和死亡率密切相关。糖尿病患者心血管事件的发生与高血糖水平有关，表现为 HbA1c 水平升高。然而，几乎没有证据表明血糖控制可以降低该人群 HF 事件的发生率。最近，尽管确切的临床影响心力衰竭发生和恶化的证据仍存在争议，但提出了几种新的抗糖尿病药物。最常见的口服抗糖尿病药物如 SGLT2、GLP-1 受体激动剂、二甲双胍和 DPP4 抑制剂，揭示了其独特的代谢和生物分子信号作用。此外，噻唑烷二酮类药物对 HF 预后、心脏功能和运动耐量的负面影响引起了极大的关注。相反，几项 GLP-1RA 的研究强调了其对心肌细胞的许多积极影响，通过 cAMP/PKA/CRCB 介导的途径减少细胞凋亡，从而对抗氧化应激。DPP-4 抑制剂的作用存在争议：沙格列汀和阿格列汀可能会增加 HF 的风险，而维格列汀和西格列汀则不会。二甲双胍通过激活 5-AMPK 增加心肌 ATP 水平，这可以解释药物与 HF 糖尿病患者事件发生率降低之间的正相关关系。新的更有趣的药物类别是 SGLT2 抑制剂，恩格列净治疗可使 HF 发生率和死亡率降低 38%，这似乎对心脏功能有积极影响。在这篇综述中，我们将分析每一类药物的具体作用，以便更好地阐明抗糖尿病药物对 HF 的临床影响，从而指导临床医生选择最佳的个体化治疗方案。
