抗结核药物固定剂量复合制剂隔日疗法临床效果分析

目的 评价国产抗结核药物固定剂量复合制剂（FDC）隔日疗法的临床应用效果,为抗结核FDC隔日疗法的推广应用提供参考依据.方法 根据两组试点市（县）地貌、人口数、总体经济状况、结核科仪器设备和工作人员水平等基本接近的原则,“抗结核药物FDC隔日疗法试点组”（简称“FDC组”）为保定市12个市（县）中纳入的初治活动性肺结核患者,共计1225例;“抗结核药物板式组合药对比观察试点组”（简称“组合药组”）为保定市另11个市（县）中纳入的初治活动性肺结核患者2328例,通过人口容量比率概率法抽取1225例患者.对两组临床治疗完成率,2、3、6个月末痰菌阴转率,疗程末X线实变阴影及空洞改变,以及不良反应等情况,用对照研究的方法进行对比观察.用统计软件包SPSS 13.0进行处理与分析,计数资料的比较采用x2检验,以P＜0.05为差异有统计学意义.结果 治疗完成率抗结核FDC组为94.53％（1158/1225）,组合药组为90.94％（1114/1225）,两组比较差异有统计学意义（x2＝11.73,P＜0.01）;2、3、6个月末痰菌阴转率抗结核FDC组分别为91.29％（262/287）、94.08％（270/287）、97.56 ％（280/287）,组合药组分别为89.05％ （244/274）、93.07％ （255/274）、96.72％（265/274）,两组比较差异均无统计学意义（x2值分别为0.79、0.24、0.36,P值均＞0.05）;FDC组疗程末X线胸片实变阴影有效吸收率及空洞改善率分别为93.06％（845/908）、89.60％（181/202）,组合药组分别为91.99％（781/849）、88.95％（169/190）,两组比较差异均无统计学意义（x2值分别为0.73、0.04,P值均＞0.05）;总不良反应发生率抗结核FDC组为21.35％（237/1110）,组合药组为22.62％（235/1039）,两组比较差异无统计学意义（x2 =0.50,P＞0.05）;实验室检测结果血常规异常、肝功能异常及肾功能异常方面,抗结核FDC组和板式组合药组相比,差异均无统计学意义（x2值分别为1.16、0.00、0.21,P值均＞0.05）.结论 国产抗结核FDC与板式组合药疗效相似,且能提高患者治疗完成率,可作为传统板式组合药的替代品.     

抗结核固定剂量复合剂与板式组合药治疗肺结核效果对比分析

目的研究国产抗结核FDC的有效性和安全性,探索适合深圳市结核病防治用药。方法从深圳市罗湖区和南山区登记的全部初治涂阳病例中随机抽取200例,其中FDC组、对照组(板式组合药)各100例,均采用全程督导的方式。对两组病人的用药剂量、临床表现、治疗效果、不良反应进行分析比较。结果(1)FDC组与对照组患者1、2、3、6个月末相关临床症状(如盗汗、发热、咳嗽、咯血、胸痛、呼吸困难、乏力)的出现率均逐渐下降,两组无显著性差异(P<0.05);(2)FDC组与对照组2个月末痰菌阴转率分别为88%、84%,6个月末痰菌阴转率提高到98%、97%,两组6个月末结核空洞闭合率分别为58.3%、48.6%,痰菌阴转率X线胸片吸收率和空洞闭合率均无显著性差异(P<0.05);(3)FDC组与对照组临床不良反应率分别为25%和18%,WBC异常率分别为18%和11%,AST异常率分别为16%和9%,TBIL异常率分别为19%和15%,临床和实验室检测的结果均无显著性差异(P<0.05);(4)FDC中利福平(R)的体质量与剂量相关系数为0.804,高于组合药中利福平(R)的体质量与剂量相关系数(0.781)。FDC组异烟肼(H)、利福平(R)、吡嗪酰胺(Z)、乙胺丁醇(E)的用药剂量低于对照组,有显著性差异(P<0.05)。结论国产FDC与板式组合药的治疗效果相同,不良反应率相近,但FDC药物的用药剂量低,具有一定的推广应用前景。     

固定剂量复合剂在国家结核病防治规划中的应用研究

目的研究固定剂量复合剂(FDC)在国家结核病防治规划中对肺结核患者治疗的可行性,为制定国家药品供用政策提供依据。方法选择4省17个县,采用固定剂量复合剂与抗结核板式组合药,对初治涂阳肺结核患者治疗效果、不良反应、治疗依从性及药品用量的对照研究。结果研究组484例初治涂阳肺结核患者中,治疗2个月和3个月末痰涂片阴转率为91.1%和95.0%,治愈率为94.6%,对照组482例初治涂阳肺结核患者中,治疗2个月和3个月末痰涂片阴转率为90.2%和92.9%,治愈率为89.4%,治愈率研究组高于对照组(P<0.05);研究组不良反应病例数90例(18.6%),对照组89例(18.5%),在不良反应病例数中,因严重不良反应中断和停止治疗病例数37例,其中,研究组10例,占研究病例总数的2.1%,对照组27例,占对照组病例总数的5.8%(P<0.05);患者在不同时期与治疗依从性有关因素的问卷调查中,反应例数不一;各省患者不同等级体质量不一。按照两种制剂用量方法计算患者口服药片数,966例患者用FDC药片数与板式组合药片数比,强化期少29.0%,继续期少8.5%。结论用FDC对初治涂阳肺结核患者治愈率达到国家结核病防治规划要求,因降低了严重药物不良反应所造成的患者中断治疗,以及患者药品片数比组合药减少,为减少耐药结核病人的发生和降低的药品成本具有重要作用,值得进一步推广应用。     

抗结核固定剂量复合剂与板式组合药治疗肺结核效果对比分析

目的研究国产抗结核FDC的有效性和安全性，探索适合深圳市结核病防治用药。方法从深圳市罗湖区和南山区登记的全部初治涂阳病例中随机抽取200例，其中FDC组、对照组（板式组合药）各100例，均采用全程督导的方式。对两组病人的用药剂量、临床表现、治疗效果、不良反应进行分析比较。结果（1）FDC组与对照组患者1、2、3、6个月末相关临床症状（如盗汗、发热、咳嗽、咯血、胸痛、呼吸困难、乏力）的出现率均逐渐下降，两组无显著性差异（P〉0．05）；（2）FDC组与对照组2个月末痰菌阴转率分别为88％、84％，6个月末痰菌阴转率提高到98％、97％，两组6个月末结核空洞闭合率分别为58．3％、48．6％，痰菌阴转率X线胸片吸收率和空洞闭合率均无显著性差异（P〉0．05）；（3）FDC组与对照组临床不良反应率分别为25％和18％，WBC异常率分别为18％和11％，AST异常率分别为16％和9％，TBIL异常率分别为19％和15％，临床和实验室检测的结果均无显著性差异（P〉0．05）；（4）FDC中利福平（R）的体质量与剂量相关系数为0．804，高于组合药中利福平（R）的体质量与剂量相关系数（0．781）。FDC组异烟肼（H）、利福平（R）、吡嗪酰胺（Z）、乙胺丁醇（E）的用药剂量低于对照组，有显著性差异（P〈0．05）。结论国产FDC与板武组合药的治疗效果相同，不良反应率相近，但FDC药物的用药剂量低，具有一定的推广应用前景。     

固定剂量复合剂在国家结核病防治规划中的应用研究

目的研究固定剂量复合剂（FDC）在国家结核病防治规划中对肺结核患者治疗的可行性，为制定国家药品供用政策提供依据。方法选择4省17个县，采用固定剂量复合剂与抗结核板式组合药，对初治涂阳肺结核患者治疗效果、不良反应、治疗依从性及药品用量的对照研究。结果研究组484例初治涂阳肺结核患者中，治疗2个月和3个月末痰涂片阴转率为91.1％和95．0％，治愈率为94.6％，对照组482例初治涂阳肺结核患者中，治疗2个月和3个月末痰涂片阴转率为90．2％和92.9％，治愈率为89．4％，治愈率研究组高于对照组（P〈0.05）；研究组不良反应病例数90例（18．6％），对照组89例（18.5％），在不良反应病例数中，因严重不良反应中断和停止治疗病例数37例，其中，研究组10例，占研究病例总数的2.1％，对照组27例，占对照组病例总数的5．8％（P〈0.05）；患者在不同时期与治疗依从性有关因素的问卷调查中，反应例数不一；各省患者不同等级体质量不一。按照两种制剂用量方法计算患者口服药片数，966例患者用FDC药片数与板式组合药片数比，强化期少29.0％，继续期少8.5％。结论用FDC对初治涂阳肺结核患者治愈率达到国家结核病防治规划要求，因降低了严重药物不良反应所造成的患者中断治疗，以及患者药品片数比组合药减少，为减少耐药结核病人的发生和降低的药品成本具有重要作用，值得进一步推广应用。     

Morisky服药依从性量表在肺结核患者中的应用

目的 通过测量和比较肺结核患者对FDC和板式组合药的服药依从性,探讨Morisky 服药依从性量表用于肺结核患者服药依从性测量的可行性。方法 在临床随机对照试验中,研究组使用FDC,对照组使用板式组合药,用Morisky 服药依从性量表对2组患者进行问卷调查。结果将Morisky 服药依从性量表用于肺结核患者时,量表的克朗巴哈α系数为0.64。共有463例肺结核患者被纳入研究,其中研究组230例,对照组233例,研究组服药依从性高于对照组,差异有统计学意义（Z=-6.001, P=0.000）。结论 FDC患者服药依从性高于板式组合药;Morisky 服药依从性量表用于肺结核患者服药依从性的测量时具有较好的内在信度和敏感性。     

国产固定剂量四/二药复合剂治疗初治涂阳肺结核患者近期疗效观察

目的评价国产固定剂量四/二药复合剂（4FDCs/2FDCs）治疗初治涂阳肺结核的疗效、不良反应、可接受性。方法选择成都市3个县（区）120例初治涂阳肺结核患者,随机分为研究（FDC）组和对照组,观察近期痰菌阴转、X线病灶改变、不良反应、可接受性。结果FDC组与对照组2月痰菌阴转率分别为88.68%、85.19%,6月后痰菌阴转率分别为100.00%、92.59%;胸部X线明显改善,FDC组与对照组分别为96.22%、92.59%,空洞缩小、闭合均为93.33%,;不良反应FDC组16例,对照组28例;服药片数FDC组较对照组强化期减少78.82%、继续期减少47.47%;治疗可接受性FDC组明显高于对照组。结论国产FDC治疗结核病高效、安全、用药片数少,易被患者接受,值得进一步推广应用。     

复治涂阳肺结核患者化疗后2个月末痰涂片阴转与未阴转情况分析

目的 分析2011-2012年复治涂阳肺结核患者强化期2个月末痰涂片检查的阴转情况,探讨当前影响复治涂阳肺结核阴转的相关因素及对转归的影响。 方法 对广州市胸科医院第二门诊辖区内登记的复治涂阳肺结核患者131例化疗后2个月末的痰进行2次抗酸染色和镜检,痰培养阳性的标本采用绝对浓度间接法进行耐药性测定。同时分析可能对痰阴转产生影响的各种因素。 结果 131例患者中化疗后2个月末未查痰涂片者13例,查后发现阴转者91例,未阴转者27例;后者3个月末阴转者15例,4个月末阴转者6例,5个月末阴转者6例。通过研究5个大变量因素,发现造成复治涂阳肺结核患者2个月末痰未能阴转的主要原因在于是否多耐药［阴转患者5.3％（3/57）,未阴转患者10.0％（2/20）;χ²＝4.457,P<0.05］或者耐多药［阴转患者28.1％(16/57),未阴转患者70.0％（14/20）;χ²＝5.456,P<0.05］、是否合并糖尿病［阴转患者12.1％（11/91）,未阴转患者25.9％（7/27）;χ²=3.973,P<0.05］。 结论 耐药或合并糖尿病是影响复治涂阳肺结核患者2个月末痰涂片阴转的关键因素。     

母牛分枝杆菌菌苗和草分枝杆菌菌苗辅助治疗初治涂阳肺结核的近期疗效观察

目的观察和评论母牛分枝杆菌菌苗和草分枝杆菌菌苗对初治涂阳肺结核的辅助治疗作用。方法将180例初治涂阳肺结核患者随机分为3组,每组60例,疗程6个月。第一组为常规抗结核药物＋母牛分枝杆菌菌苗,第二组为常规抗结核药物＋草分枝杆菌菌苗,第三组为单纯抗结核药物。分别在治疗前、治疗后1个月末、2个月末、4个月末、6个月末时痰菌的转阴情况,X线胸片显示病变吸收情况。结果治疗1个月末3组病变吸收和痰涂片转阴率无明显差异;治疗6个月末,母牛分枝杆菌和草分枝杆菌组病变吸收率及痰涂片转阴率均明显高于对照组。结论母牛分枝杆菌和草分枝杆菌明显改变肺结核患者细胞免疫功能,加快病变的吸收和痰菌的转阴速度,两种免疫辅助药疗效相当。     

抗结核药品合理化使用核查方法的探讨

目的 探讨药品使用核查的方法,间接评价药品使用的合理性。 方法 采取典型调查的方法,选择河南省（县1、县2）、重庆市（县3、县4）和吉林省（县5、县6）,共6个县作为调查现场,通过全国结核病防治季报表获得各结核病防治机构肺结核患者发现和治疗转归等信息,同时查阅各结核病防治机构药品出入库登记本和患者病历获得药品出入库数量、过期破损数量和断货天数等信息。根据指标定义计算缺货率、过期破损率、正确处方率和药品使用核查差异度（参考区间定为±25%）等指标。2007年1-12月,调查现场共发现新发涂阳肺结核患者2122例,复治涂阳肺结核患者202例,涂阴肺结核患者1596例。新发涂阳肺结核患者2个月末痰检未阴转率为6.03%（128/2122）;复治涂阳肺结核患者2个月末痰检未阴转率为7.92%（16/202）。 结果 调查现场缺货率为1.78%［234/（36×365）］,过期破损率为0.57%［2159/（125 544+250 440）］;按整群抽样调查的方法调查了1200例肺结核患者,均按照《中国结核病防治规划实施工作指南（2008年版）》的要求开出正确处方,正确处方率100%;HRZE板式组合药使用核查差异度为－41.93%［（84.378－119 760）/84.378］,最高为－12.1%［（13 140－14 730）/13 140］,最低为－86.36%［（10 673－19 890）/10 673］,其中县4、县5和县6差异度低于－25%;HR板式组合药使用核查差异度为－28.60%［（173 475－223 080）/173 475］,最高为－14.05%［（34 470－39 600）/34 470］,最低为－114.51%［（17 761－38 100）/17 761］,其中县5和县6差异度低于－25%;HRE板式组合药使用核查差异度为31.22%［（26 434－18 180）/26 434］,最高为90.91%［（3960－360）/3960］,最低为3.52%［（2985－2880）/2985）］,其中县1、县2和县5差异度高于25%。 结论 通过比较理论与实际消耗量差异的方法进行药品使用核查,可以粗略评价抗结核治疗中合理化用药的情况,建议每6个月或1年开展一次。     

Fixed-dose combination chemotherapy (Rifater/Rifinah) for active pulmonary tuberculosis in Taiwan: a two-year follow-up.

SETTING: Veterans General Hospital-Taipei, Taiwan. OBJECTIVE: To assess the efficacy and safety of a fixed-dose combination (FDC) of Rifater (RFT)/Rifinah (RFN) in the treatment of newly diagnosed smear-positive pulmonary tuberculosis. DESIGN: Patients were randomly assigned to two 6-month short-course chemotherapy regimens. One group of patients was treated with FDCs and another was given the four component drugs (INH, RMP, EMB and PZA) as separate formulations. RESULTS: The 105 patients enrolled in the study were divided into two treatment groups. Fifty-one patients who had completed treatment without interruption, 26 in the FDC group and 25 in the separate regimen, were eligible for analysis at the end of 2 years. Among the patients with a drug susceptibility test result available, four in the FDC group had bacilli resistant to pyrazinamide. In the separate regimen group, two patients had bacilli resistant to ethambutol and six had bacilli resistant to pyrazinamide. The two regimens were of similar effectiveness with regard to sputum conversion, compliance and radiological improvement. No patient with FDC treatment developed gastointestinal symptoms, visual disturbance or peripheral neuropathy (P < 0.05). However, FDC treatment resulted in drug-induced fever in one patient. One patient (3.8%) in the FDC group relapsed 5 months after completing treatment. CONCLUSION: This study suggests that the two regimens had similar effectiveness in the treatment of smear-positive pulmonary tuberculosis. However, the fewer adverse drug events among those patients treated with the FDC regimen suggests that it has a better safety profile.     

Initial treatment with fixed-dose combination rosiglitazone/glimepiride in patients with previously untreated type 2 diabetes

Aim: This study assessed the efficacy and safety of two different dosing regimens of fixed‐dose combination (FDC) rosiglitazone (RSG) plus glimepiride (GLIM) compared with RSG or GLIM monotherapy in drug‐naive subjects with type 2 diabetes mellitus (T2DM). Methods: Drug‐naive subjects (n = 901) were enrolled into this 28‐week, double‐blind, parallel‐group study if their glycosylated haemoglobin A_1c (HbA_1c) was >7.5% but ≤12%. Subjects were randomized to receive either GLIM [4 mg once daily (OD) maximal], RSG (8 mg OD maximal) or RSG/GLIM FDC regimen A (4 mg/4 mg OD maximal) or RSG/GLIM FDC regimen B (8 mg/4 mg OD maximal). Patients were assessed for efficacy and safety every 4 weeks for the first 12 weeks of the study, and at weeks 20 and 28. The primary efficacy endpoint was change in HbA_1c from baseline. Key secondary endpoints included the proportion of patients achieving recommended HbA_1c and fasting plasma glucose (FPG) targets; change from baseline in FPG, insulin, C‐reactive protein (CRP), adiponectin, free fatty acids and lipids; and percentage change in homeostasis model assessment‐estimated insulin sensitivity and β‐cell function. Safety evaluations included adverse‐event (AE) monitoring and clinical laboratory evaluations. Results: At week 28, both RSG/GLIM FDC regimens significantly reduced HbA_1c (mean ± s.d.: ?2.4 ± 1.4% FDC regimen A; ?2.5 ± 1.4% FDC regimen B) to a greater extent than RSG (?1.8 ± 1.5%) or GLIM (?1.7 ± 1.4%) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 vs. both RSG and GLIM). Significantly more subjects achieved HbA_1c target levels of ≤6.5 and <7% with either RSG/GLIM FDC regimen compared with RSG or GLIM alone (model‐adjusted odds ratio, p < 0.0001 for both comparisons). Similarly, a significantly greater reduction in FPG levels was observed in subjects treated with the RSG/GLIM FDC [mean ± s.d. (mg/dl): ?69.5 ± 57.5 FDC regimen A; ?79.9 ± 56.8 FDC regimen B) compared with RSG (?56.6 ± 58.1) or GLIM (?42.2 ± 66.1) monotherapy (model‐adjusted mean treatment difference, p < 0.0001 for both comparisons). Improvement in CRP was also observed in subjects who were treated with a RSG/GLIM FDC or RSG monotherapy compared with GLIM monotherapy. RSG/GLIM FDC was generally well tolerated, with no new safety or tolerability issues identified from its monotherapy components, and a similar AE profile was observed across FDC regimens. The most commonly reported AE was hypoglycaemia, and the incidence of confirmed symptomatic hypoglycaemia (3.6–5.5%) was comparable among subjects treated with an RSG/GLIM FDC and GLIM monotherapy. Conclusions: Compared with RSG or GLIM monotherapy, the RSG/GLIM FDC improved glycaemic control with no significant increased risk of hypoglycaemia. RSG/GLIM FDC provides an effective and well‐tolerated treatment option for drug‐naive individuals with T2DM.     

固定剂量复合剂治疗肺结核患者依从性调查与分析

目的调查和分析固定剂量复合剂(FDC)治疗肺结核的患者依从性,为FDC在我国推广应用提供参考。方法选择4省17县结防机构登记的966例初治涂阳肺结核患者,随机分为研究组和对照组,使用统一调查问卷,调查患者不同治疗时期依从性。结果在治疗前调查961例患者回答问题,899例(93.5%)自愿接受治疗;研究组选择每日服药比例86.8%,高于对照组的42.1%,组间有显著性差异(P<0.01)。强化期末,261例(28.3%)感到坚持治疗有困难,213例(23.1%)认为医生督导是坚持治疗的原因。疗程末,138例(15.5%)认为坚持治疗的关键是医生。结论采用固定剂量复合剂患者依从性优于对照组,药片数量减少是提高依从性原因之一,应加以推广;随疗程进展,医生督导作用下降,应加强对患者强化期的管理和督导。     

四联抗结核固定剂量复合剂的临床疗效研究

目的研究四联抗结核固定剂量复合剂的近期疗效及安全性。方法将广东省湛江市6个县区登记的540例初治涂阳肺结核病人分为研究组和对照组,用对照研究方法对2组病例的临床症状、治疗效果和不良反应等进行对比研究。结果(1)研究组治愈率为94.4%,对照组为92.2%,2组的治愈率比较差异无统计学意义(χ2=1.071,P=0.301);(2)2组患者相关临床症状(如咳嗽、胸痛、乏力、盗汗、低热、咯血)逐渐得到改善,2组比较差异无统计学意义(P0.05);(3)2、3个月末研究组痰菌阴转率分别为90.7%、94.1%,对照组分别为89.6%,91.9%,比较差异无统计学意义(P0.05);X线胸片显示空洞愈合方面,研究组的空洞闭合率为78.2%,对照组为61.2%,研究组比对照组高。(4)研究组与对照组的不良反应发生率分别为21.5%和20.0%,比较差异无统计学意义(P0.05);强化期对照组的消化道不良反应发生率明显大于研究组(P0.05);2组血常规、肝功能异常率接近;研究组因不良反应停药率高于对照组(P0.05)。结论四联FDC与板式组合药具有同等的抗结核疗效,不良反应发生率相近,并且在治疗管理方面显示出较大的优势,建议推荐在我国结核病防治规划中应用。     

Epidural corticosteroid injections for sciatica: a randomised,double blind,controlled clinical trial

OBJECTIVE: To determine the efficacy of epidural corticosteroid injections for sciatica. METHODS: Three epidural injections (two day intervals) of 2 ml prednisolone acetate (50 mg) or 2 ml isotonic saline were administered to patients with sciatica presumably due to a disk herniation lasting 15-180 days. Self evaluation was the main judgment criterion at day 20. Patients who recovered or showed marked improvement were considered as success. Pain measured by VAS, the SLR test, Schober's test, Dallas pain questionnaire, and the Roland-Morris index were evaluated at days 0, 5, 20, and 35. Only analgesics were authorised, patients requiring non-steroidal anti-inflammatory drugs (NSAIDs) before day 20 were considered as failure. RESULTS: 42 patients were included in the control group (CG), 43 in the steroid group (SG). On an intention to treat analysis 15/42 (36%) in the CG and 22/43 (51%) in the SG (p=0.15) were considered as success (difference 15.5%, 95% CI (-5.4 to 36.3)). Among the 48 failures, 14 patients (6 CG, 8 SG) required NSAIDs, 3 (2 CG, 1 SG) required surgery, and 7 (3 CG, 4 SG) other treatments. On analysis according to protocol, in 74 remaining patients 12/35 (34%) in the CG and 22/39 (56%) in the SG (p=0.057) were considered as success (difference 22.1%, 95% CI (0.0 to 44.2)). For all secondary end points intragroup improvement with time was significant, but intergroup differences were not. CONCLUSION: The efficacy of isotonic saline administered epidurally for sciatica cannot be excluded, but epidural steroid injections provide no additional improvement.     

Alterations of LXRα and LXRβ expression in the hypothalamus of glucose-intolerant rats

Liver X receptor (LXR) α and β are nuclear receptors that are crucial for the regulation of carbohydrate and lipid metabolism. Activation of LXRs in the brain facilitates cholesterol clearance and improves cognitive deficits, thus they are considered as promising drug targets to treat diseases such as atherosclerosis and Alzheimer's disease. Nevertheless, little is known about the function and localization of LXRs in the brain. Here, we studied the expression of LXR in the brains of rats that received free access to 10% (w/v) fructose group (FG) in their beverages or water control drinks (control group (CG)). After 6 weeks rats in the FG presented with hypertriglyceridemia, hyperinsulinemia, and became glucose intolerant, suggesting a progression toward type 2 diabetes. We found that hypothalamic LXR expression was altered in fructose-fed rats. Rats in the FG presented with a decrease in LXRβ levels while showing an increase in LXRα expression in the hypothalamus but not in the hippocampus, cerebellum, or neocortex. Moreover, both LXRα and β expression correlated negatively with insulin and triglyceride levels. Interestingly, LXRβ showed a negative correlation with the area under the curve during the glucose tolerance test in the CG and a positive correlation in the FG. Immunocytochemistry revealed that the paraventricular and ventromedial nuclei express mainly LXRα whereas the arcuate nucleus expresses LXRβ. Both LXR immunosignals were found in the median preoptic area. This is the first study showing a relationship between glucose and lipid homeostasis and the expression of LXRs in the hypothalamus, suggesting that LXRs may trigger neurochemical and neurophysiological responses for the control of food intake and energy expenditure through these receptors.     

Twice-daily and three-times-daily dosing of a repaglinide/metformin fixed-dose combination tablet provide similar glycaemic control

Aim: To assess the efficacy and safety of a new repaglinide/metformin fixed-dose combination (FDC) tablet administered either twice a day (BID) or three times a day (TID) for the management of type 2 diabetes.
Methods: This was a 26-week, multicentre, open-label parallel trial in which subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to instead receive repaglinide/metformin FDC either BID or TID or a rosiglitazone/metformin FDC BID. Two primary hypotheses were tested in a hierarchical manner: (i) treatment with the repaglinide/metformin FDC BID is non-inferior to that of the rosiglitazone/metformin FDC BID as measured by changes in haemoglobin A1c (HbA1c) (results presented in companion paper) and (ii) repaglinide/metformin BID is non-inferior to repaglinide/metformin TID (as measured by changes in HbA1c). Additional efficacy and safety end-points were also assessed.
Results: A total of 561 subjects were randomized; 383 completed the study. Repaglinide/metformin FDC BID was non-inferior to repaglinide/metformin FDC TID with respect to HbA1c. Additionally, changes in mean fasting plasma glucose values from baseline to end of study were not significantly different between the BID and the TID dose groups. There were no major hypoglycaemic episodes reported in either group during the trial, and overall adverse event profiles were similar.
Conclusion: The efficacy of twice-daily dosing of a repaglinide/metformin FDC tablet was non-inferior to that of three-times-daily dosing.