Simultaneous Determination of Sitagliptin Phosphate Monohydrate and Metformin Hydrochloride in Tablets by a Validated UPLC Method

A novel approach was used to develop and validate a rapid, specific, accurate and precise reverse phase ultra performance liquid chromatographic (UPLC) method for the simultaneous determination of Sitagliptin phosphate monohydrate and Metformin hydrochloride in pharmaceutical dosage forms. The chromatographic separation was achieved on Aquity UPLC BEH C8 100 × 2.1 mm, 1.7 μm, column using a buffer consisting of 10 mM potassium dihydrogen phosphate and 2 mM hexane-1-sulfonic acid sodium salt (pH adjusted to 5.50 with diluted phosphoric acid) and acetonitrile as organic solvent in a gradient program. The flow rate was 0.2 mL min(-1) and the detection wavelength was 210 nm. The limit of detection (LOD) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.2 and 0.06 μg mL(-1), respectively. The limit of quantification (LOQ) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.7 and 0.2 μg mL(-1), respectively. This method was validated with respect to linearity, accuracy, precision, specificity and robustness. The method was also found to be stability-indicating.     

Effects of DPP-4 inhibition on cardiac metabolism and function in mice

Type 2 diabetes is associated with an increased risk of cardiac complications. Inhibitors of dipeptidylpeptidase 4 (DPP-4) are novel drugs for the treatment of patients with type 2 diabetes. The effect of DPP-4 inhibitors on myocardial metabolism has not been studied in detail. In wild-type C57Bl6-mice, 3 weeks of treatment with sitagliptin had no effect on body weight and glucose tolerance nor on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoAcarboxylase (ACC), phosphofructokinase-2 (PFK2) or tuberin-2 (TSC2) in the left ventricular myocardium. However, in 10 week old db/db−/− mice, a model of diabetes and obesity, sitagliptin potently reduced plasma glucose rise in peritoneal glucose tolerance tests and reduced weight increase. The myocardium of untreated db/db−/− mice exhibited a marked increase of the phosphorylation of AMPK, ACC, TSC2, expression of p53 and fatty acid translocase (FAT/CD36) membrane expression. These changes were reduced by DPP-4 inhibition. Sitagliptin showed no effect on cardiomyocyte size but prevented myocardial fibrosis in the 10 week old db/db−/− mice and reduced expression of TGF-β1, markers of oxidative stress and the accumulation of advanced glycation end products in cardiomyocytes. Working heart analyses did not show an effect of sitagliptin on parameters of systolic cardiac function. In animals with diabetes and obesity, sitagliptin improved glucose tolerance, reduced weight gain, myocardial fibrosis and oxidative stress. Furthermore the study provides evidence that treatment with sitagliptin decreases elevated myocardial fatty acid uptake and oxidation in the diabetic heart. These observations show beneficial myocardial metabolic effect of DPP-4 inhibition in this mouse model of diabetes and obesity.     

Dipeptidyl peptidase-4 inhibitor for steroid-induced diabetes

The addition of the dipeptidyl peptidase-4 (DDP-4) inhibitor has been reported to achieve greater improvements in glucose metabolism with fewer adverse events compared to increasing the metformin dose in type 2 diabetic patients. We present a patient with steroid-induced diabetes whose blood glucose levels were ameliorated by the use of the DPP-4 inhibitor, showing that the DPP-4 inhibitors may be an effective and safe oral anti-diabetic drug for steroid-induced diabetes.     

Dipeptidyl peptidase-4: A key player in chronic liver disease

Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor.     

利拉鲁肽、西他列汀和吡格列酮治疗NAFLD合并2型糖尿病患者疗效初步比较研究

目的 探讨利拉鲁肽、西他列汀和吡格列酮治疗非酒精性脂肪性肝病（NAFLD）合并2型糖尿病患者的疗效。方法 2013年1月～2015年12月我院收治的150例NAFLD合并2型糖尿病患者被随机分成胰高糖素样肽-1、西他列汀和吡格列酮治疗组,每组50例,分别接受相应药物治疗3 m。结果 胰高糖素样肽-1治疗组患者治疗后体质量、BMI、AST、ALT、空腹血糖、HbA1c和AST/血小板计数比值分别为【（67.3±5.2） kg、（27.3±3.1） kg/m2、（52.6±11.5） U/ml、（75.5±10.8） U/ml、（9.4±1.7） mmol/L、（8.4±1.2） mmol/L、何（0.75±0.21）】,西他列汀组患者治疗后ALT、空腹血糖和HbA1c水平分别为【（78.8±14.2） U/ml、（9.8±1.4） mmol/L、（8.7±1.5） mmol/L、）】,吡格列酮组患者治疗后AST、HbA1c和甘油三酸脂水平分别为【（48.4±8.9） U/ml、（8.0±1.6） mmol/L、和（2.8±0.8） mmol/L、】。结论 相比之下,胰高糖素样肽-1能够显著降低NAFLD合并2型糖尿病患者体质量,改善肝功能和血脂水平。     

西格列汀治疗2型糖尿病的疗效

目的观察西格列汀治疗2型糖尿病的疗效及其安全性。方法将随机选择的50名2型糖尿病患者分为2组,对照组继续口服降糖药或注射胰岛素,治疗组在原有降糖基础上加用西格列汀口服。治疗12周后观察两组患者空腹血糖、餐后2小时血糖、糖化血红蛋白、血脂、肝肾功能、体重变化、不良反应等。结果两组患者空腹血糖、餐后2小时血糖、糖化血红蛋白均有下降,但西格列汀组下降尤为明显(p<0.05),两组间血脂、肝肾功能、体重指数、不良反应相比无明显差异。结论西格列汀治疗2型糖尿病安全、有效。     

盐酸小檗碱联合西格列汀治疗肥胖2型糖尿病的疗效观察

目的探讨盐酸小檗碱联合西格列汀治疗肥胖2型糖尿病的临床疗效。方法选取2014年8月—2015年8月在武安市第一人民医院内分泌科接受治疗的肥胖2型糖尿病患者96例为研究对象,按治疗方案的差别分为对照组和治疗组,每组各48例。对照组口服磷酸西格列汀片,100 mg/次,1次/d。治疗组在对照组基础上口服盐酸小檗碱片,0.3 g/次,3次/d,餐前口服。两组患者均连续治疗12周。观察两组的临床疗效,比较两组患者的血糖指标和炎症指标。结果治疗后,对照组和治疗组的总有效率分别为83.33%、95.83%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者的空腹血糖(FPG)、餐后2 h血糖及糖化血红蛋白(Hb A1c)均明显降低,同组治疗前后差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者的C-反应蛋白(CRP)、白细胞介素-6(IL-6)、内皮素-1(ET-1)及血栓素2(TXB2)均显著下降,而前列腺素Fla(PGFla)、一氧化氮(NO)均显著上升,同组治疗前后差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论盐酸小檗碱联合西格列汀治疗肥胖2型糖尿病具有较好的临床疗效,能明显降低患者血糖,改善炎症指标,具有一定的临床推广应用价值。     

二甲双胍与西格列汀对非酒精性脂肪肝病大鼠肝脏FGF21及SREBP-1c mRNA表达的影响

目的比较二甲双胍及西格列汀对高脂饮食诱导大鼠肝脏FGF21 mRNA及SREBP-1c mRNA的作用。方法将60只SD大鼠随机分为正常组20只(普通饲料,NC组)及高脂组40只(高脂饮食,HF组),喂养8周后,每组随机抽取10只,比较后证实HF组NAFLD模型成功建立。继将HF组分3组:二甲双胍干预组(HF+M,10只)[加二甲双胍500 mg/(kg·d)]、西格列汀干预组(HF+XI,10只)[加西格列汀10 mg/(kg·d)]及高脂组(HF1,10只)(等体积生理盐水)。灌胃8周末处死,检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA)含量,空腹血糖(FBG)及胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR);HE染色观察肝脏病理形态学的变化;Real-time PCR检测肝组织FGF21 mRNA及SREBP-1c mRNA表达的变化。结果两种药物均可降低血清ALT、AST活性(P<0.05),减少TC、TG、FFA含量,FBG、肝脏TG含量及HOM A-IR(P<0.05);西格列汀可明显改善大鼠肝脏脂肪变,效果优于二甲双胍;二甲双胍可下调肝组织SREBP-1c mRNA表达量,上调FGF21 mRNA表达量(P<0.01),而西格列汀可同时降低肝脏FGF21 mRNA及SREBP-1c mRNA表达量(P<0.01)。结论西格列汀与二甲双胍均可有效减少肝脏TG含量,但西格列汀改善肝组织病理变化较二甲双胍明显,而二甲双胍减轻HOM A-IR强于西格列汀;同时,二者均可不同程度影响肝组织SREBP-1c与FGF21 mRNA表达量。     

糖尿病患者起始胰岛素治疗方案的选择及安全性评价

【摘要】目的 探讨口服二甲双胍控糖效果不佳糖尿病患者起始胰岛素治疗方案的选择及安全性。方法 选取口服二甲双胍控糖效果不佳的2型糖尿病患者126例随机分为3组,在二甲双胍治疗基础上,分别联用西格列汀、起始剂量10 U/d胰岛素、起始剂量15 U/d胰岛素分别作为A组、B组、C组,治疗期间均根据血糖控制情况调整用药剂量,达到并维持空腹血糖≤56 mmol/L。记录3组血糖达标率、达标时间、低血糖反应;计算治疗前后体重指数(BMI)、体重差值,统计三组治疗前后空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋(HbA1c)、胰岛素抵抗指数(HOMA IR)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL C)。结果〓本研究中A组5例脱落,B组7例脱落,C组8例脱落。3组患者血糖达标率、低血糖反应发生率比较差异无统计学意义(P＞005);C组血糖达标时间短于A组、B组(P＜005),但A组、B组比较差异无统计学意义(P＞005)。3组治疗后FPG、2hPG、HbA1c、HOMA IR均下降,FINS上升,同组治疗前后差异有统计学意义(P＜005),但3组组间比较差异无统计学意义(P＞005)。A组治疗前后BMI、体重差值低于B组、C组,差异有统计学意义(P＜005),但B组、C组比较差异无统计学意义(P＞005)。结论〓口服二甲双胍控糖效果不佳2型糖尿病患者联合西格列汀、甘精胰岛素均可获得理想的降糖效果,且加大基础甘精胰岛素方案起始用药剂量可缩短血糖达标时间,但西格列汀在控制体重上更具优势。     

磷酸西格列汀联合二甲双胍治疗肥胖2型糖尿病合并心力衰竭的疗效及其对患者炎性因子的影响

目的 探讨磷酸西格列汀联合二甲双胍对肥胖2型糖尿病合并心力衰竭的疗效及其对患者炎性因子的影响.方法 于2014年1月至2015年12月在宝鸡市中心医院选择156例肥胖2型糖尿病合并心力衰竭患者,采用随机数字表法将其随机分为观察组(磷酸西格列汀+甘精胰岛素+二甲双胍)与对照组(甘精胰岛素+二甲双胍),每组78例,分别于治疗前及治疗1个月、3个月后测定并比较患者的空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖基化血红蛋白(HbA1c)、体质量指数(BMI)、α肿瘤坏死因子(TNF-α)、C反应蛋白(CRP)、白细胞介素-6(IL-6)及心功能.结果 观察组患者治疗1个月和3个月后的FPG[分别为(5.81±0.76)mmol/L、(5.46±0.43)mmol/L]、2 hPG[分别为(8.60±1.21)mmol/L、(8.06±0.67)mmol/L]、HbA1c[分别为(6.82±0.92)%、(6.31±0.55)%]均低于对照组相应值[FPG分别为(6.31±0.57)mmol/L、(6.13±0.31)mmol/L;2 hPG分别为(14.51±3.32)mmol/L、(15.70±2.11)mmol/L;HbA1c分别为(9.11±11.19)%、(9.03±0.88)%],差异均有统计学意义(P<0.05);治疗3个月后,观察组患者的BMI为(27.37±2.15),低于对照组的(30.45±3.17),差异有统计学意义(P<0.05);治疗1个月和3个月后,观察组患者的HR[分别为(94.48±14.38)次/min、(81.43±12.57)次/min]均低于对照组[分别为(107.53±12.45)次/min、(92.82±10.76)次/min],LVEF[分别为(69.47±7.45)%、(76.12±5.89)%]和Ea/Aa比值[分别为(1.33±0.23)、(1.48±0.16)]均高于对照组[LVEF分别为(58.95±6.34)%、(65.14±6.33)%;Ea/Aa比值分别为(1.26±0.17)、(1.33±0.21)],差异均有统计学意义(P<0.05);治疗1个月和3个月后,观察组患者的TNF-α[分别为(110.38±19.33)μg/mL、(84.56±16.63)μg/mL]、CRP[分别为(7.16±0.62)mg/L、(5.86±0.78)mg/L]和IL-6[分别为(307.62±38.45)μg/mL、(243.52±25.76)μg/mL]均低于对照组相应值[TNF-α分别为(124.62±18.69)μg/mL、(99.73±16.75)μg/mL;CRP分别为(7.67±0.76)mg/L、(7.24±1.13)mg/L;IL-6分别为(356.67±36.74)μg/mL、(319.35±29.38)μg/mL],差异均有统计学意义(P<0.05).结论 磷酸西格列汀联合二甲双胍能明显改善肥胖2型糖尿病合并心力衰竭患者的血糖及心功能,并抑制炎性因子,值得临床推广应用.