Potential anti-inflammatory effect of dapagliflozin in HCHF diet- induced fatty liver degeneration through inhibition of TNF-α, IL-1β, and IL-18 in rat liver

Non-alcoholic fatty liver (NAFLD) is accompanied by an increased expression of oxidative stress parameters, in addition to the inflammatory cytokines; tumor necrosis factor alpha (TNF-α), interleukin type 1beta (IL-1β), and interleukin type 18 (IL-18). The aim of this study is to investigate the effect of dapagliflizon (DAPA) on high carbohydrate-high fat (HCHF) diet-induced expression of inflammatory cytokines in rat liver. NAFLD was induced by feeding the rats HCHF diet (consist of animal fat tallow and standard show pellets) and the consumption of fructose in drinking water (10%) for 12 or 18 weeks. The oral administration of DAPA (1 mg/kg/day) from 13th week to 18th week significantly improved NAFLD as indicated by a significant reduction in liver aminotransferases in addition to a significant decrease of serum MDA, cholesterol, triglyceride and LDL-cholesterol with concomitant significant elevation of HDL-cholesterol. DAPA-treated animals showed a significant reduction of liver homogenate content of TNF-α, IL-1β, and IL-18. These results indicate that the administration of DAPA may be beneficial against HCHF diet-induced NAFLD. Histopathological examination of liver specimens supported the conclusion that DAPA improves steatohepatitis induced by HCHF diet.     

达格列净治疗84例糖尿病肾病的临床疗效观察

目的：描述在真实世界中达格列净对于糖尿病肾病治疗的疗效和安全性。方法： 在我院服用达格列净的84例糖尿病肾病患者中,回顾性分析达格列净对于血糖、血压、体重、血脂、蛋白尿、肾功能的疗效,比较治疗前后临床治疗的差异性,并记录治疗过程中的副作用以评价其安全性。结果：84例患者平均年龄52.47岁,男性56 例(66.7%),平均糖尿病病史8年,合并肥胖或超重34例(40.4%),合并糖尿病视网膜病变患者47 例(56.0%),高血压69 例(82.1%),平均24小时蛋白尿3.1 g/天,平均eGFR 87.1 ml/min/m²。在随访过程中,共有12例(14.3%)停用达格列净(男性4例、女性8例)。女性更容易发生泌尿系感染(p=0.024,OR=10.0)。达格列净显著降低糖化血红蛋白(p<0.001),空腹血糖(p<0.001)、胰岛素用量(p<0.001)、体重(p=0.02)、BMI(p=0.02)、收缩压(p=0.04)、蛋白尿(p=0.05)。结论：本研究依据真实世界的观察性数据,支持达格列净相对安全,是糖尿病肾病治疗的一个良好选择。     

雷公藤多苷联合达格列净治疗糖尿病肾病的疗效分析

目的 探讨雷公藤多苷联合达格列净治疗糖尿病肾病的临床疗效。方法 将2020年1月—2021年6月本院确诊的2型糖尿病肾病患者120例,按照随机数表法分为对照组及观察组,每组患者60例。两组均进行常规治疗,在此基础上对照组给予达格列净治疗,观察组给予雷公藤多苷联合达格列净治疗。比较两组的临床治疗效果,包括治疗前后的肾功能指标、代谢指标,同时记录治疗过程中出现的不良反应。结果 治疗效果方面,观察组的血肌酐、24小时尿蛋白定量均较对照组下降,血白蛋白较对照组升高,肾功能指标差异具有统计学意义（P＜0.05）;两组的空腹血糖、糖化血红蛋白、血尿酸水平均较治疗前明显下降,但组间无统计学差异（P＞0.05）。不良反应方面,观察组和对照组治疗后低血糖、肝功损害等相关不良反应发生率分别为8.33%和6.67%,但差异无统计学意义（P＞0.05）。结论 在糖尿病肾病的治疗中,雷公藤多苷联合达格列净可有效降低患者血肌酐和尿蛋白水平,升高血清白蛋白,进而改善患者的肾脏预后,同时不良反应无明显增加,整体临床效果较理想。     

Sodium glucose co-transporter inhibitors for the management of diabetes mellitus: an opinion paper from the Endocrine and Metabolism Practice and Research Network of the American College of Clinical Pharmacy

Type 2 diabetes mellitus (T2DM) carries a high prevalence in the United States and worldwide. Therefore, the number of medication classes being developed and studied has grown. The individualized management of diabetes is accomplished by evaluating a medication’s efficacy, safety, and cost, along with the patient’s preference and tolerance to the medication. Sodium glucose co-transporter 2 inhibitors are a new therapeutic class indicated for the treatment of diabetes and have a unique mechanism of action, independent of beta-cell function. The first agent approved by the Food and Drug Administration (FDA) was canagliflozin in March 2013. Two agents – dapagliflozin and empagliflozin – were FDA-approved in January and July 2014, respectively. A clear understanding of the new class is needed to identify its appropriate use in clinical practice. Members of the American College of Clinical Pharmacy Endocrine and Metabolism Practice and Research Network reviewed available literature regarding this therapeutic class. The article addresses the advantages, disadvantages, emerging role, and patient education for sodium glucose co-transporter 2 inhibitors. Key limitations for this article include limited access to clinical trial data not published by the pharmaceutical company and limited data on products produced outside the United States.     

Chronopharmacology of dapagliflozin-induced antihyperglycemic effects in C57BL/6J mice

Chronopharmacology is the study of the varying responses of drugs to changes in biological timing and endogenous periodicities. The selective sodium-glucose cotransporter 2 inhibitor, dapagliflozin, is a globally prescribed antihyperglycemic drug. Although dapagliflozin is usually administered once a day, the specific intake time is generally not mentioned. Therefore, this study aimed at investigating the diurnal effects of dapagliflozin on high-fat diet (HFD)-induced obesity in mice. Five-week-old male C57BL/6J mice were fed a normal (control) diet or HFD for 10 weeks. During the last 2 weeks, the mice were administered olive oil/ethanol emulsion or dapagliflozin (1 mg/kg, p.o.) in the light or dark phase. At the end of the experiment, the mice were euthanized after an 18 h fasting period, and plasma and tissue samples (epididymal white adipose tissues, liver, and kidney) were collected. Dapagliflozin administration in the light phase significantly decreased plasma glucose levels, insulin levels, adipose adipokines, and decreased the size of adipocytes, compared with the HFD group. In contrast, these parameters remained unchanged in the mice treated during the dark phase. Our data therefore suggests that dapagliflozin portrays definite chronopharmacology, which may provide valuable information on the importance of drug administration timing for maximal pharmacological effects.     

Commentary: SGLT inhibitors in type 1 diabetes: Place in therapy and a risk mitigation strategy for preventing diabetic ketoacidosis - the STOP DKA protocol

In the accompanying article, Goldenberg et al. review the promotion of diabetic ketoacidosis by SGLT2 inihibitors. They have carried out a metanalysis showing a 3.5-fold increase in the risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes under treatment with SGLT2 inhibitors. They make a number of suggestions for attempting to mitigate the risk of DKA in these patients, notably including blood ketone monitoring and the use of supplemental carbohydrates with additional insulin when ketones suggest incipient DKA. Their proposal merits evaluation in a clinical trial involving type 1 diabetes, which should also assess the possible cardiorenal benefits demonstrated with treatment with SGLT2 inhibitors in type 2 diabetes.     

达格列净联合比格列酮治疗2型糖尿病的临床研究

目的探讨达格列净片联合吡格列酮片治疗2型糖尿病的临床疗效。方法选取2018年1月—2019年1月深圳市第二人民医院收治的86例2型糖尿病患者纳入本研究,根据用药方案之间的差异将患者分为对照组和治疗组,每组各43例。对照组于早饭前口服吡格列酮片,2片/次,1次/d。治疗组在对照组的基础上于早晨口服给予达格列净片,0.5片/次,1次/d。两组患者均治疗3个月。观察两组患者临床疗效,同时比较治疗前后两组患者血糖指标、氧化应激指标水平。结果治疗后,对照组、治疗组总有效率分别为72.1%、90.7%,两组总有效率比较差异具有统计学意义(P0.05)。治疗后,两组空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)水平均显著降低,胰高血糖素样肽1(GLP-1)水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组血糖指标均明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)、总抗氧化能力(T-Aoc)水平均显著升高,丙二醛(MDA)水平显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组氧化应激指标均明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论达格列净片联合吡格列酮片治疗2型糖尿病具有较好的临床疗效,可改善患者血糖水平,缓解氧化应激状态,具有一定的临床推广应用价值。     

津力达颗粒联合达格列净治疗老年2型糖尿病的临床研究

目的探讨津力达颗粒联合达格列净片治疗老年2型糖尿病的临床效果。方法选取2017年9月—2019年5月内蒙古自治区人民医院收治的84例2型糖尿病老年患者,随机分成对照组(42)和治疗组(42例)。对照组晨服达格列净片,10mg/次,1次/d。治疗组在对照组基础上口服津力达颗粒,1袋/次,3次/d。两组均连续治疗12周。观察两组患者临床疗效,同时比较治疗前后两组患者体质量指数(BMI)值、外周血中性粒细胞与淋巴细胞比值(NLR)、胰岛素抵抗(HOMA-IR)值、胰岛β细胞功能(HOMA-β)值及血清糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、C反应蛋白(CRP)、淀粉样蛋白A(AA)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平。结果治疗后,对照组和治疗组总有效率分别为81.0%、95.2%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者血清HbA1c、FPG和2 h PG水平及BMI值均显著低于治疗前(P0.05),且治疗组下降程度比对照组更显著(P0.05)。治疗后,两组患者外周血NLR值和血清CRP、AA水平均显著降低(P0.05),且治疗组上述微炎症标志物均显著低于对照组(P0.05)。治疗后,两组患者HOMA-IR值及血清MDA水平较治疗前均显著降低(P0.05),而HOMA-β值和血清SOD水平均显著增加(P0.05),且治疗组以上指标的改善效果更明显(P0.05)。结论津力达颗粒联合达格列净片治疗老年2型糖尿病的整体疗效确切,有助于控制血糖,改善机体微炎症状态,纠正体内氧化应激,保护胰岛功能。     

达格列净联合利拉鲁肽治疗2型糖尿病的临床研究

目的 探究达格列净联合利拉鲁肽治疗2型糖尿病患者的临床效果。方法 收集2017年1月—2019年4月在郑州人民医院治疗的2型糖尿病患者126例,随机分为对照组（63例）和治疗组（63例）。对照组口服盐酸二甲双胍片,0.5 g/次,3次/d,同时于睡前皮下注射利拉鲁肽注射液0.6 mg,1周后根据患者肠道反应增加至1.2 mg,1次/d。治疗组早餐前口服达格列净片,10 mg/次,1次/d;利拉鲁肽注射液的用法同对照组。两组患者治疗时间均为3个月。观察两组患者临床疗效,同时比较治疗前后两组患者糖化血红蛋白（HbA1c）、空腹血糖（FPG）、餐后2 h血糖（2 h PG）、体质量指数（BMI）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、对纤溶酶原激活物抑制物-1（PAI-1）和胱抑素C（CysC）水平。结果 治疗后,对照组和治疗组临床有效率分别为79.37%和93.65%,两组比较差异有统计学意义（P<0.05）。治疗后,两组患者HbA1c、FPG、2 h PG、BMI、IL-6、TNF-α、PAI-1、CysC均显著降低（P<0.05）,且治疗组上述指标比对照组更低（P<0.05）。结论 达格列净联合利拉鲁肽治疗2型糖尿病患者效果显著,且不增加不良反应,降低发生糖尿病血管并发症的风险。     

达格列净联合二甲双胍治疗2型糖尿病的临床效果分析

目的观察不同药物方案治疗2型糖尿病(T2DM)的效果。方法选择2019年8月—2020年7月收治的128例T2DM患者,分为I、II组,均用二甲双胍治疗,II组联合达格列净,比较两组治疗情况。结果治疗后,II组FPG、2 hPG、HbAlc、HOMA-IR、FIns分别为(7.10±1.45)mmol/L、(8.12±1.95)mmol/L、(6.67±1.07)%、(3.01±1.09)、(14.31±3.55)mmol/L,和同期I组(9.12±1.54)mmol/L、(9.84±2.01)mmol/L、(8.03±1.42)%、(4.57±0.04)、(11.42±3.43)mmol/L,差异有统计学意义(t=3.284、4.257、3.257、3.875、4.527,P=0.040、0.037、0.041、0.039、0.035<0.05);I、II组不良反应发生率分别为12.50%、10.94%,差异无统计学意义(χ²=0.076,P=0.783>0.05)。结论采用达格列净与二甲双胍联合方案治疗T2DM,能更好的控制血糖水平,疗效确切,且安全性较高。