Exenatide and sitagliptin are not associated with increased risk of acute renal failure: a retrospective claims analysis

Aim: This study evaluated whether the risk of acute renal failure (ARF) increases with exenatide and sitagliptin use. Methods: A retrospective cohort study of a large medical and pharmacy claims database was performed. Data for 4 91 539 patients were analysed. Cox proportional hazard models were used to compare the risk of ARF between diabetic and non‐diabetic subjects and between diabetic patients treated with exenatide, sitagliptin and control medications. Results: Adjusted Cox analyses showed diabetic subjects had a higher risk of ARF [HR 1.51, confidence interval (CI) 1.26–1.81, p < 0.001] than non‐diabetic controls. Compared with diabetic controls, neither exenatide (HR 0.77, CI 0.42–1.41, p = 0.40) nor sitagliptin (HR 1.17, CI 0.82–1.65, p = 0.39) increased the risk of ARF. Conclusion: Our study revealed an increased incidence of ARF in diabetic versus non‐diabetic patients but no association between use of exenatide or sitagliptin and ARF. Because of the limitations of this observational analysis, we cannot exclude the possibility of a very small increased risk.     

Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood-retinal barrier in a type 2 diabetes animal model

Aim: The aim of this study was to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV inhibitor (DPP‐IV), in preventing the deleterious effects of diabetes on the blood–retinal barrier in male Zucker Diabetic Fatty (ZDF) rats. Methods: ZDF rats at 20 weeks of age were treated with sitagliptin (10 mg/kg/day) during 6 weeks. The effect of the drug on glycaemia was assessed by evaluating glycated haemoglobin (HbA1c). The content and/or distribution of tight junction (TJ) proteins occludin and claudin‐5, as well as nitrotyrosine residues, interleukin (IL)‐1β, BAX and Bcl‐2 was evaluated in the retinas by western blotting and/or immunohistochemistry. Retinal cell apoptosis was assessed by the terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL) assay. The number of CD34+ cells present in peripheral circulation was assessed by flow cytometry, and endothelial progenitor cells (EPC) adhesion ability to the retinal vessels was evaluated by immunohistochemistry. Results: Sitagliptin improved glycaemic control as reflected by a significant decrease in HbA1c levels by about 1.2%. Treatment with sitagliptin prevented the changes in the endothelial subcellular distribution of the TJ proteins induced by diabetes. Sitagliptin also decreased the nitrosative stress, the inflammatory state and cell death by apoptosis in diabetic retinas. Diabetic animals presented decreased levels of CD34+ cells in the peripheral circulation and decreased adhesion ability of EPC to the retinal vessels. Sitagliptin allowed a recovery of the number of CD34+ cells present in the bloodstream to levels similar to their number in controls and increased the adhesion ability of EPC to the retinal vessels. Conclusions: Sitagliptin prevented nitrosative stress, inflammation and apoptosis in retinal cells and exerted beneficial effects on the blood–retinal barrier integrity in ZDF rat retinas.     

Cardiovascular effects of sitagliptin – An anti‐diabetes medicine

Dipeptidyl‐peptidase‐4 (DPP‐4) inhibitors, as the most recent available anti‐diabetic agents, were generally used in clinical treatment of type 2 diabetes (T2DM). In addition to anti‐diabetic effects, the five most widely used DPP‐4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin) also exert cardiovascular protective effects. In recent years, increasing studies suggest that sitagliptin shows pleiotropic impacts towards the cardiovascular system either with or without diabetes. In this review, we summarized the recent reports to provide an update discussion about cardiovascular protective effects of sitagliptin and the corresponding mechanisms. Sitagliptin has positive effects towards ischaemic cardiovascular diseases, atherosclerosis and hypertension. These effects are mainly conducted through DPP‐4 inhibitions. In addition, sitagliptin exerts anti‐inflammation, anti‐oxidative stress, anti‐apoptosis, mediation on lipid accumulation and so on, which also contribute to its cardiovascular effects.     

西格列汀联合二甲双胍治疗2型糖尿病伴非酒精性脂肪肝的临床研究

目的观察西格列汀联合二甲双胍治疗2型糖尿病(T2DM)伴非酒精性脂肪肝(NAFLD)的临床疗效和安全性。方法将94例2型糖尿病伴非酒精性脂肪肝患者随机分为对照组和试验组,每组47例。对照组口服二甲双胍0.5 g,每天2次;试验组在对照组的基础上,晨起口服西格列汀0.1 g,每天1次。2组均持续用药4个月。比较2组患者的临床疗效,胰岛素抵抗指数(HOMA-IR),胰岛β细胞功能(HOMA-β),血糖及肝功能,并观察2组患者的药物不良反应发生情况。结果治疗后,试验组和对照组的总有效率分别为82.98%(39例/47例)和61.70%(29例/47例),差异有统计学意义(P<0.05)。试验组和对照组HOMA-IR分别为1.06±0.08和1.13±0.11,HOMA-β分别为85.70±10.07和65.83±7.20,空腹血糖(FPG)分别为(6.07±0.76)和(6.66±0.80)mmol·L^-1,餐后2 h血糖(2 h PG)分别为(8.63±1.07)和(9.36±1.40)mmol·L^-1,糖化血红蛋白(Hb A1c)分别为(5.84±0.69)%和(6.39±0.77)%,谷丙转氨酶(ALT)分别为(30.76±3.77)和(38.37±3.72)mmol·L^-1,谷草转氨酶(AST)分别为(34.06±4.04)和(40.20±4.69)mmol·L^-1,差异均有统计学意义(均P<0.05)。对照组出现便秘2例,腹痛4例,上呼吸道感染4例,药物不良反应发生率为21.28%(10例/47例);试验组出现便秘3例,腹痛2例,上呼吸道感染3例,药物不良反应发生率为17.02%(8例/47例),差异无统计学意义(P>0.05)。结论西格列汀联合二甲双胍对2型糖尿病伴非酒精性脂肪肝患者的疗效优于单用二甲双胍,能够降低HOMA-IR,提高HOMA-β水平。     

Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague–Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.     

Current perspectives in treatment of angina pectoris

Intravenous immunoglobulin is an important method of treating idiopathic thrombocytopenic purpura, especially when a rapid platelet response is desired. Dr Besa explains how to use this therapy in acute and chronic purpura in both children and adults. He also describes the four preparations available and discusses efficacy, cost, and safety.     

西格列汀联合二甲双胍治疗2型糖尿病伴心血管疾病患者的疗效观察及对IMT、Hcy水平、血流动力学的影响

目的:探究西格列汀联合二甲双胍治疗2型糖尿病伴心血管疾病患者的疗效观察及对IMT、Hcy水平、血流动力学的影响.方法:2012年6月~2015年7月收治的180例确诊为2型糖尿病合并心血管疾病的患者,根据随机数字表法,平均分为观察组及对照组,每组90例.比较两组患者血糖(FBG),糖化血红蛋白(HbA1c)、空腹胰岛素(FIN)、胰岛素抵抗指数(HOMA-IR)、颈动脉内膜中层厚度(IMT),同型半胱氨酸(Hcy)水平,球后血流动力学水平.结果:治疗后观察组与对照组的FBG、HbA1c、FIN、HOMA-IR均明显改善,观察组患者FBG、HbA1c、FIN水平较对照组改善更为明显;观察组患者IMT、Hcy水平明显下降,且显著低于对照组;两组患者视网膜中央动脉(CRA),睫状后动脉(PCA)的血流速度均较治疗前有明显改善,且观察组上述指标明显高于对照组.结论:西格列汀联合二甲双胍治疗2型糖尿病可有效降低各血糖指标的同时降低IMT及Hcy含量,增强眼底微循环,明显改善糖尿病血管病变,值得临床推广.     

New combination treatments in the management of diabetes: focus on sitagliptin – metformin

Type 2 diabetes mellitus is an increasingly prevalent condition worldwide. The complications of this disease are known to significantly increase the morbidity and mortality of those affected, resulting in substantial direct and indirect costs. Although good glycemic control has been shown to reduce the incidence and progression of diabetes-related microvascular complications, blood glucose levels are not adequately controlled in most individuals with diabetes. The reasons for this are many, and include issues such as poor adherence to complex medication regimes; costs of prescribed therapies; and the failure of traditionally prescribed medications to preserve beta cell function over time. However, our armamentarium of glucose-lowering drugs has expanded recently with the development of medications that act via the incretin pathway. Sitagliptin, the first commercially available dipeptidyl peptidase-4 inhibitor, inhibits the metabolism and inactivation of the incretin hormones GLP-1 and GIP. The subsequent elevation in levels of these hormones and associated prolongation of their actions has been shown to increase insulin secretion and suppress glucagon secretion in a glucose-appropriate fashion. Sitagliptin therapy in individuals with type 2 diabetes has been found to lower significantly hemoglobin A1c (Hb1c) levels with a minimum of adverse side effects such as weight gain or hypoglycemia. Use of sitagliptin in conjunction with the insulin-sensitizing medication metformin has been shown to decrease HbA1c levels more significantly than does either drug alone. This combination of medications is generally well tolerated, with no adverse effects on weight and a very low likelihood of treatment-related hypoglycemia. Use of both drugs will positively affect many of the underlying metabolic abnormalities associated with type 2 diabetes, including the disordered secretion of insulin and glucagon as well as impaired sensitivity to insulin which are known to accompany this disease. Animal studies also suggest that dipeptidyl peptidase-4 inhibitor treatment may help to preserve beta cell mass; however, it is unclear at present whether or not this will prove to be the case in humans.