复方黄芪颗粒治疗慢性乙型肝炎疗程与疗效关系分析

目的：观察复方黄芪颗粒治疗慢性乙型肝炎（chronical hepatitis B，CHB）疗程与疗效间的关系。方法：104例HBV DNA和／或HBeAg阳性CHB患者给予口服复方黄芪颗粒治疗，于治疗0周、12周、24周、36周、48周检测生化及病毒学指标。结果：①治疗12周、24周、36周、48周时，HBV DNA阴转率分别为36．14％（30／83例）、51．56％（33／54例）、81．82％（9／11例）、66．67％（14／21例），治疗36周时最高，与其他疗程对比，P〈0.05。②治疗12周、24周、36周、48周时，HBeAg阴转率分别为35．42％（17／48例）、31．71％（13／41例）、50．00％（2／4例）、40．00％（4／10例），治疗36周时最高，但与其他疗程对比，P〉0．05。③治疗12周、24周、36周、48周时，ALT复常率分别为51．81％（43／83例）、63．64％（42／66例）、75．00％（6／8例）、87．50％（7／8例），治疗48周时最高，与其他疗程对比，P〉0．05。（少治疗12周、24周、36周、48周时，治疗总有效率分别为64．29％（63／98例）、69．23％（54／78例）、75．00％（6／8例）、70．00（7／10例）。结论：复方黄芪颗粒具有比较好的抑制HBV及恢复肝功能作用，随治疗时间延长，疗效有一定提高，在36周时总有效率达高峰，之后仍持续在较高水平。     

格华止治疗单用胰岛素血糖控制不佳糖尿病观察

选择40例单用胰岛素治疗控制不佳的2型糖尿病患者。在应用优必林70／30胰岛素治疗基础上，加格华止1500mg／天，分3次饭后服，共12周，比较治疗前、后FPG、PPG等并进行统计学分析。结果：与第0周相比，治疗后第4周、第8周、第12周的血糖谱均有显著下降（P〈0．01）；第12周BMI、HbA1c、TG、LDL-C有显著下降（P〈0．01），而TC、HDL-C、FCP、UAE、CR均无明显变化（P〉0．05）；治疗后第12周，平均全日胰岛素总量比治疗前分别减少了22．5％。结论：格华止具有降低胰岛素抵抗，提高胰岛素敏感性，保护B细胞分泌功能作用。     

巴曲酶对血管性认知障碍的疗效观察

目的探讨巴曲酶治疗血管性认知障碍（VCI）的安全性和疗效。方法选择缺血性脑血管病所致、有认知功能障碍，但未达到痴呆标准的VCI患者80例，随机分为巴曲酶组和对照组，每组40例。巴曲酶组分别于入院后第1、8和第12周隔日给予巴曲酶静脉滴注（5U巴曲酶加入250ml等渗盐水），1次／d，4次／周。所有患者常规使用阿司匹林。采用简易精神状态量表（MMSE）和13常生活能力量表（ADL）评价认知功能及日常生活能力；并检测治疗前、后纤维蛋白原（FIB）水平，评估药物安全性。结果①巴曲酶组在治疗前及治疗后第8周，MMSE和ADL评分与对照组差异无统计学意义（P〉0．05）；在第12周，MMSE和ADL评分较治疗前，差异有统计学意义（P〈0．05），但较对照组差异无统计学意义（P〉0．05）；在第16周，MMSE和ADL评分较治疗前和对照组均有明显改善（P〈0．05）。而对照组在第8、12及16周，MMSE和ADL评分较治疗前变化不明显（P〉0．05）。②巴曲酶组第1周治疗前、后FIB分别为（3．50±0．59）、（1．95±0．43）g／L、第8周治疗前、后分别为（3．22±0．54）、（2．18±0．46）g／L，第12周治疗前、后分别为（2．75±O．41）、（2．40±0．41）g／L，治疗前、后差异均有统计学意义（P〈0．01）。对照组第1、8、12周FIB分别为（3．39±O．61）、（3．30±0．59）、（3．24±0．56）g／L，差异无统计学意义（P〉0．05）。③巴曲酶组有1例、对照组有2例出现脑梗死复发（P〉0．05）。巴曲酶组未发生药物过敏，颅内、消化道出血等不良事件。结论巴曲酶有助于改善VCI患者的认知功能，提高患者的日常生活能力，药物安全性良好。     

白花香莲解毒方联合阿德福韦酯对HBeAg阳性慢性乙望肝炎患者病毒学及生存质量的影响

目的：通过观察壮药白花香莲解毒方联合阿德福韦酯对HBeAg阳性的慢性乙型肝炎（CHB）患者病毒学及生存质量的影响，评估其临床疗效。方法：采用多中心随机临床研究方法，将240例HBeAg阳性的CHB患者随机分为治疗组和对照组，对照组给予阿德福韦酯胶囊10mg／次，1；L,／d，治疗组在对照组基础上加用白花香莲解毒方，两次／d，疗程为48周。分别观察治疗12周、24周、48周两组患者在病毒学、生存质量（QOL）、慢性肝病量表（CLDQ）评分情况。结果：①病毒学方面：从治疗12周始，治疗组HBVDNA下降的对数值与对照组比较，差异有显著性意义（P〈0．05）；治疗组治疗12周、24周病毒学应答率分别为65．48％（74例）、82．3％（92例），对照组为51．78％（58例）、70．53％（79例），差异有显著性意义（P〈0．05）；治疗48周，两组患者总的病毒学应答率比较差异无显著性意义（P〉0．05）；治疗组治疗12周、24周、48周的HBVDNA阴转率分别为22．12％（25例）、43．36％（49例）、57．52％（65例），对照组为11．61％（13例）、21．4％（24例）、32．14％（36例），差异有显著性意义（P〈0．05）。②QOL方面：治疗24周，治疗组在生理领域、心理领域改善作用优于对照组；治疗48周治疗组在总的生存质量、总的健康状况、生理领域、心理领域、社会关系领域均优于对照组，两组比较差异有显著性意义（P〈0．05）。③CLDQ评分方面：治疗24周，治疗组患者在乏力、情感功能、焦虑三方面改善程度优于对照组；治疗48周治疗组患者在乏力、全身症状、情感功能、焦虑四方面改善程度优于对照组，两组比较差异有显著性意义（P〈0．05）。④不良事件：两组患者主要不良反应为头痛、腹痛、恶心；研究期间共发生磷酸肌酸激酶（CK）升高9例，发生率为4％。结论：白花香莲解毒方联合阿德福韦酯治疗HBeAg阳性CHB患者，能显著提高其对HBVDNA的抑制作用，改善患者生存质量。     

替比夫定治疗失代偿期乙型肝炎肝硬化临床观察

目的观察替比夫定治疗失代偿期乙型肝炎（乙肝）肝硬化24周的疗效与安全性。方法将40例乙肝肝硬化失代偿期患者随机分为治疗组和对照组,每组各20例。对照组予以常规支持、对症治疗;治疗组在此基础上加用替比夫定600mg／d抗病毒治疗,疗程均为24周。分别于治疗前及治疗4、12、24周时检测患者肝功能、血清肌酸激酶、凝血酶原活动度、乙肝病毒血清标志物、HBVDNA定量,同时观察临床症状、体征及不良反应等,并进行Child-Pugh评分。结果治疗4周时,治疗组与对照组ALT复常率和HBV DNA转阴率分别为20．5％和5．0％,25．0％和5．0％;治疗12周时,2组ALT复常率和HBVDNA转阴率分别为60．0％和15．0％,100．0％和10．0％;治疗24周时,2组ALT复常率和HBVDNA转阴率分别为70．0％和25．0％,100．0％和10．0％,HBeAg转阴例数分别为9例和1例。治疗12周时治疗组与对照组Child～Pugh评分分别下降至（6．5±0．9）分和（7．8±0．9）分;治疗24周时分别下降至（5．2±0．9）分和（7．1±0．9）分。2组均未发现明显的不良反应。结论替比夫定治疗乙肝肝硬化失代偿期患者有良好的疗效与安全性。     

急性心肌梗死早期应用卡托普利对QRS积分的影响

为探讨急性心肌梗死（AMI）早期应用卡托普利对心肌梗死范围的影响，将74例AMI病人随机分为治疗组（常规＋卡托普利治疗）和对照组（常规治疗），均观察4周，分别于治疗前，治疗后第24h、72h、1周、2周、3周、4周描记一次标准12导联心电图，按Nancy标准进行QRS记分。结果：共62例完成试验观察。治疗前两组QRS积分无显著性差异（P＞0．05）；治疗后1周时，治疗组（n=30）QRS积分显著低于对照组（P＜0．05），与治疗前比较虽有增高，但差异无显著性（P＞0．05），对照组（n=32）QRS积分显著高于治疗前（P＜0．01）；第4周时，治疗组QRS积分显著低于对照组及治疗前（均P＜0．05），对照组与治疗前比较虽有降低，但差异无显著性。提示：卡托普利在AMI早期应用有限制心肌梗死范围作用。     

恩替卡韦治疗拉米夫定失效慢性乙型肝炎一年的疗效

目的评价恩替卡韦（ETV）对拉米夫定（LVD）失效的慢性乙型肝炎（CHB）患者治疗1年的疗效和安全性。方法选择LVD治疗失效的CHB患者145例，按4：1比例随机分为ETV组（1．0mg／d）116例和安慰剂组29例，治疗12周后，所有患者进入36周的开放用药阶段（ETV1．0mg／d）。观察血清HBVDNA水平、乙型肝炎e抗原（HBeAg）、肝生化功能的变化和不良事件的发生率。结果经12周的治疗，ETV组患者血清HBVDNA平均下降4．30log10拷贝／ml（聚合酶链反应法），安慰剂组下降0．15log10拷贝／ml（P＜0．01）。第12周时，在基线丙氨酸转氨酶（ALT）异常的患者中，ETV组的ALT复常率明显高于安慰剂组（分别为68％与6％，P＜0．01）。两组间不良事件的总发生率相当（33％与28％）。经48周的治疗，服用ETV48周患者HBVDNA的下降幅度为5．08log10拷贝／ml；服用ETV36周患者HBVDNA的下降幅度为4．86log10拷贝／ml；在治疗前ALT异常的患者中，上述两组ALT的复常率分别是85％和90％。治疗结束时，在基线HBeAg阳性的患者中，有6．2％（8／129）出现血清学转换。在治疗期间，未发生与耐药相关的变异。每天服用ETV1．0mg，持续48周的安全性和耐受性良好。结论ETV（1．0mg／d）治疗LVD失效的CHB患者具有显著的抗病毒和临床疗效。     

结核分枝杆菌Ag85A／ESAT-6嵌合型质粒DNA疫苗和抗结核药物联合治疗小鼠耐药结核病的效果研究

目的研究结核分枝杆菌Ag85A／ESAT-6嵌合型质粒DNA疫苗和抗结核药物联合治疗小鼠耐药结核病的效果。方法用结核分枝杆菌高耐利福平低耐异烟肼临床分离株HB240尾静脉注射BALB／c小鼠1个月后，将小鼠随机分成2组，第1组用利福平（RFP）、异烟肼（INH）治疗12周，第2组用RFP、INH和结核分枝杆菌Ag85A／ESAT-6嵌合型质粒DNA疫苗（免疫5次）联合治疗12周；治疗结束后4和8周，分别取肺、肝和脾观察病理改变、称取质量、作菌落计数。结果治疗结束后4和8周，第2组小鼠体质量均超过第1组，但无显著性差异（P〉0．05）。治疗结束后4周，第2组肺、脾脏指数（0．017，0．011）均略低于第1组（0，020，0，012）（P〉0．05）；治疗结束后8周，第2组肺、肝脏指数（O．021，0．047）均略低于第1组（0．022，0．048）（P〉0．05）；而第2组脾脏指数（0．008）显著低于第1组（0．012）（P〈0．05）。治疗结束后4周，第2组有4例脾脏未见明显病变，第1组仅1例脾脏未见明显病变；治疗结束后8周，第2组有1例肺门淋巴结肿大，而第1组有3例；第2组有5例脾脏未见明显病变，第1组仅2例脾脏未见明显病变。治疗结束后4周，第2组肺菌落计数和脾菌落计数比第1组显著减少，分别减少70％和80％。结论DNA疫苗和抗结核药物联合治疗小鼠耐药结核病疗效高于单纯化疗。     

自体骨髓间充质干细胞对肝硬化患者门静脉高压血流动力学的影响

目的观察白体骨髓间充质干细胞对乙型肝炎肝硬化失代偿患者门静脉血流动力学的影响。方法将2011年02月-2012年01月收治的乙型肝炎肝硬化失代偿住院患者46例配对分为两组。治疗组23例,对照组23例。两组患者在性别、年龄、诊断、生化及影像学指标方面差异无统计学意义。所有患者在签定知情同意书后进行治疗。对照组仅给予抗病毒及护肝利尿支持等治疗。治疗组抽取自体骨髓200ml,体外分离纯化骨髓间充质干细胞在体外诱导培养后制成10ml细胞悬液,经肝动脉注入肝脏,分别在治疗后第8、12周观察患者的门静脉血流动力学指标的变化。组内比较采用配对t检验,组间比较采用成组t检验。结果经骨髓间充质干细胞治疗8周和12周,治疗组门静脉内径（DPV）和脾静脉内径（DSV）下降,DPV在8周和12周分别为（13．26±1．3l）和（12．83±1．38）mm,与治疗前比较,t值为2．290和3．421,P〈0．05和P〈0．01;DSV在8周和12周分别为（8．39±1．38）和（8．02±1．24）mm,与治疗前比较,t值为2．079和2．787,P〈0．05和P〈0．01。与同期对照组比较,DPV在8周和12周t值为2．382和2．602,P值均〈0．05;DSV在8周和12周t值为3．236和4．185,P值均〈0．01,差异均有统计学意义。门静脉最大血流速度（PVX）增快,8周和12周分别为（20．72±4．63）和（20．58±3．46）cm／s,与治疗前比较,t值为2．833和3．198,P值均〈0．01,差异有统计学意义。与同期对照组（17．12±4．78）和（17．20±3．87）cm／s比较,差异有统计学意义（t值为2．530和3．123,P〈0．05和P〈0．01）。结论自体骨髓间充质干细胞可以明显改善乙型肝炎肝硬化失代偿患者的门静脉血流动力学指标。     

诺和龙和诺和灵N治疗2型糖尿病临床观察

选择30例T2DM患者合用诺和灵N及诺和龙治疗，每周根据血糖调整剂量，在0周及12周测定血糖及体重等。结果：12周后FBG下降4mmol／L、PBG下降5．5mmol／L、HbA1c下降2．9％，P〈0．01。无一例低血糖等不良事件发生。结论：诺和灵N与诺和龙联合治疗可以有效地降低FBG、PBG和HbA1c，同时具有良好的安全性。     

In type 2 diabetes patients, insulin glargine is associated with lower postprandial release of intact proinsulin compared with sulfonylurea treatment

Objective

Our objective was to investigate how postprandial processing of intact proinsulin is influenced by different pharmacological strategies in type 2 diabetes mellitus (T2DM).

Materials/Methods

This exploratory, nonrandomized, cross-sectional study recruited T2DM patients and healthy subjects. Upon recruitment, eligible T2DM patients had been treated for ≥6 months with insulin glargine (GLA) plus metformin (MET), sulfonylureas (SU) plus MET, or dipeptidyl-peptidase-4 inhibitors (DPP-4-I) plus MET. Blood samples were drawn from study participants after an 8 h fast and at regular intervals for up to 5 h after consumption of a standardized meal. Study endpoints included postprandial intact proinsulin and insulin levels and the insulin/proinsulin ratio.

Results

As expected, postprandial secretion of proinsulin was greater in all T2DM treatment groups than in healthy subjects (p < .01 for all comparisons). Postprandial release of proinsulin was significantly greater in T2DM patients treated with SU plus MET than in those treated with GLA plus MET (p = .003). Treatment with DPP-4-I plus MET was associated with reduced proinsulin secretion versus SU plus MET and an increased insulin/proinsulin ratio versus the other T2DM groups.

Conclusions

Treatment of T2DM with GLA plus MET or DPP-4-I plus MET was associated with a more physiological postprandial secretion pattern of the β cell compared with those treated with SU plus MET.     

The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-being

AIM: As many overweight people with T1DM are insulin resistant, adjuvant therapy with insulin sensitising agents, such as metformin, may be beneficial. This study evaluated the effect of adjuvant metformin in T1DM on insulin sensitivity, diabetic control, body composition, quality of life (QOL) and treatment satisfaction. MATERIALS AND METHODS: A 3-month prospective open-labelled pilot study of 16 patients aged 18-40 with T1DM and body mass index (BMI) >25 kg/m(2) was performed. The patients received 500-850 mg metformin twice daily. Insulin sensitivity, assessed by a frequently sampled intravenous glucose tolerance test [n=5], body composition, HbA(1c) and quality of life (QOL) were measured before and after treatment. A retrospective review of 30 patients with T1DM treated with metformin for at least 4 months was also performed. BMI, HbA(1c) and insulin requirements during metformin treatment was compared to pre-metformin data, and to patients treated with insulin only. RESULTS: In the pilot study, insulin sensitivity increased significantly from 0.86 +/- 0.33 x 10(-4)/min/(microU/ml) to 1.17 +/- 0.48 x 10(-4)/min/(microU/ml) after 3 months adjuvant therapy (p = 0.043). This was associated with a decreased insulin requirement and mean daily blood glucose. There were no significant changes in HbA(1c) or body composition. QOL significantly improved (p < 0.002). The retrospective review revealed an initial reduction in HbA(1c) (0.8 +/- 1.4%, p = 0.001). This effect diminished with prolonged treatment. BMI decreased in patients remaining on metformin for a 2-year period (0.5 +/- 0.5kg/m(2), p = 0.042). CONCLUSION: Adjuvant metformin can improve QOL, insulin sensitivity and glycaemic control in overweight adults with T1DM.     

New therapies for type 2 diabetes: what place for incretin-based agents and rimonabant compared to the previous ones?

Treatment of type 2 diabetes (T2DM) is based on lifestyle changes and oral antidiabetic agents or insulin. The UKPDS study has confirmed metformin (Met) as the initial monotherapy. Accordingly, Met is widely regarded as the first drug of choice for most patients with T2DM. Safety and efficacy of sulphonylureas (SU) have been confirmed by several clinical trials. Recently, thiazolidinediones (TZD) have addressed some aspects of insulin-resistance that characterized several T2DM patients. However, SU and TZD are associated with various side effects that limit their use in many patients. New agents have been recently developed which potentiate the activity of the incretin (GLP1). GLP1, a gut hormone secreted in response to meal ingestion, is rapidly degraded by dipeptidylpeptidase-4 (DPP-4). GLP1 enhances insulin secretion and inhibits glucagon secretion in a glucose-dependent manner, delays gastric emptying and, in animal studies, preserves beta-cell mass by reducing apoptosis and stimulates of beta-cell proliferation. GLP1 levels are abnormally low in T2DM patients. Two classes of agents based on GLP1 have been launched: DPP-4 inhibitors and DPP-4 resistant GLP1 analogues. Randomized studies confirmed their efficacy to improve glycemic control in T2DM patients. Orally administered DPP-4 inhibitors reduce HbA1c by 0.5-1.1%, without hypoglycaemic events and no weight gain. The sub-cutaneous injected GLP1 analogues (exenatide and liraglutide) show larger reductions in HbA1c by 0.8-1.7% and weight loss but are associated with gastrointestinal side effects contributing to a significant treatment interruption. Several studies support the use of DPP-4 inhibitors in combination with Met as a promising second line treatment.     

二甲双胍调节糖尿病大鼠心房小电导钙激活钾通道亚型蛋白表达的信号通路

目的探讨蛋白激酶A(PKA)/钙调蛋白Ⅱ(CaMKⅡ)信号通路在二甲双胍(Met)调节2型糖尿病(T2DM)大鼠心房小电导钙激活钾通道亚型KCa2.2和KCa2.3蛋白表达中的作用。方法健康雄性Wistar大鼠40只,随机选8只喂普通饲料为对照组(Con组),另32只喂高脂高糖饲料联合腹腔注射小剂量链脲佐菌素构建T2DM大鼠模型后,再随机分为DM组、Met组、H-89组(腹腔注射PKA抑制剂H-89)和KN-93组(腹腔注射CaMKⅡ抑制剂KN-93),每组8只。用ELISA检测大鼠心房组织PKA活性,qRT-PCR检测CaMKⅡmRNA表达,Western blot和免疫组织化学检测KCa2.2、KCa2.3和磷酸化CaMKⅡ(p-CaMKⅡ)蛋白表达。结果 Con组、DM组、Met组和H-89组PKA活性分别为0.74±0.04、0.50±0.05、0.69±0.03和0.48±0.03。与DM组比较,Met组PKA活性明显提升(P<0.01);与Met组比较,H-89组显著抑制PKA活性(P<0.01)。Con组、DM组及Met组CaMKⅡmRNA分别为1.00±0.07、0.61±0.03和0.92±0.09。与Con组比较,DM组CaMKⅡmRNA表达明显降低(P<0.01);与DM组比较,Met组CaMKⅡmRNA表达明显增加(P<0.01)。与Con组比较,DM组心房组织p-CaMKⅡ和KCa2.2蛋白表达均明显降低,KCa2.3蛋白表达明显升高(P<0.01)。与DM组比较,Met组明显提升p-CaMKⅡ和KCa2.2蛋白表达,明显抑制KCa2.3蛋白表达(P<0.01)。与Met组比较,KN-93组和H-89组分别显著抑制p-CaMKⅡ蛋白表达和PKA活性,均显著下调KCa2.2蛋白表达,上调KCa2.3蛋白表达(P<0.01)。免疫组织化学染色显示,与Met组比较,KN-93组和H-89组均显著下调KCa2.2蛋白表达,上调KCa2.3蛋白表达(P<0.05,P<0.01),与Western blot检测结果一致。结论 Met通过激活PKA/CaMKⅡ信号通路部分修复T2DM大鼠心房KCa2.2蛋白下调和KCa2.3蛋白上调。     

An observational study of reduction of insulin resistance and prevention of development of type 2 diabetes mellitus in women with polycystic ovary syndrome treated with metformin and diet

Our first specific aim in an observational study of 431 nondiabetic women with polycystic ovary syndrome (PCOS), aged >or=20 years and with >or=11 months follow-up on metformin diet, was to prospectively assess relationships between pretreatment glucose and insulin resistance (IR) and the development of type 2 diabetes mellitus (T2DM) or gestational diabetes (GD). Our second specific aim was to determine whether development of T2DM and GD was independently associated with lesser reduction of IR on metformin diet when compared with women who remained free of T2DM and GD. Women with body mass index <25 kg/m(2) and those with body mass index >or=25 kg/m(2) were, respectively, instructed in a 2000- or 1500-cal/d, high-protein (26% of calories), low-carbohydrate (44%) diet, with 30% of calories as fat and a polyunsaturate-saturate ratio of 2:1. Three groups of women with PCOS were categorized: (a) 17 with no previous GD, who developed T2DM on metformin diet (mean +/- SD follow-up, 49 +/- 33 months), (b) 401 with no previous GD and free of T2DM on metformin diet (follow-up, 38 +/- 25 months), and (c) 13 with either previous GD or GD on metformin diet (follow-up, 38 +/- 25 months). On metformin diet, women who developed T2DM vs those who remained free of T2DM had higher pretreatment glucose (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03-1.16; P = .003) and homeostasis model assessment of insulin resistance (HOMA-IR) (OR, 1.22; 95% CI, 1.04-1.42; P = .01), and less reduction of HOMA-IR (OR, 0.82; 95% CI, 0.72-0.92; P = .0008). On metformin diet, women either with previous GD or who developed GD vs those who remained free of T2DM had less reduction of HOMA-IR (OR, 0.88; 95% CI, 0.78-0.99; P = .03). By repeated-measures analysis, on metformin diet, women who did not develop T2DM had reduction in HOMA-IR (P < .0001), with the slope of this curve different (P = .002) from the unchanged IR exhibited by women who developed T2DM and different (P = .017) from an increased IR slope (P = .049) in women who had GD. In women with PCOS, pretreatment glucose and IR, and lesser reduction in IR on metformin diet were associated with T2DM and GD.     

Should Metformin Remain First-Line Medical Therapy for Patients with Type 2 Diabetes Mellitus and Atherosclerotic Cardiovascular Disease? An Alternative Approach

Purpose of Review

With recent cardiovascular outcome trial (CVOT) results for antihyperglycemic medications, the treatment algorithm for patients with type 2 diabetes (T2DM) and atherosclerotic vascular disease (ASCVD) requires revision.

Recent Findings

All completed CVOTs have demonstrated CV safety of the tested medications, with some trials demonstrating CV efficacy. While metformin remains the first-line recommended medication for T2DM, 18–37% of the patients enrolled in the completed CVOTs were not treated with metformin, providing substantial power to assess CV outcomes independent of metformin. The safety and tolerability of metformin are indisputable, but there are no robust data proving its efficacy for either macro or microvascular disease outcomes. We should reconsider the primacy of metformin in the management of T2DM in patients with ASCVD.

Summary

This article will review the evidence for CV effects of antihyperglycemic agents (AHAs), and propose an evidence-based treatment algorithm for patients with T2DM and ASCVD.

     

Glucose-lowering treatment and clinical results in 163 121 patients with type 2 diabetes: an observational study from the Swedish national diabetes register

Aims: To analyse clinical characteristics and treatment results in unselected type 2 diabetes mellitus (T2DM) patients, with non‐pharmacological treatment as well as the most commonly used pharmacological glucose‐lowering treatment regimens, in everyday clinical practice. Methods: In this population‐based cross‐sectional study, information was linked from the Swedish National Diabetes Register, Prescribed Drug Register and Patient Register. T2DM patients with non‐pharmacological treatment and T2DM patients continuously using the 12 most common pharmacological treatment regimens were included in the study (n = 163121). Results: There were statistically significant differences in clinical characteristics between the groups. Patients with insulin‐based treatment regimens had the longest duration of diabetes and more cardiovascular risk factors than the T2DM‐population in general. The proportion of patients reaching HbA1c ≤7% varied between 70.1% (metformin) and 25.0% [premixed insulin (PMI) + SU) in patients with pharmacological treatment. 84.8% of the patients with non‐pharmacological treatment reached target. Compared to patients on metformin, patients on other pharmacological treatments had a lower likelihood, with hazard ratios ranging from 0.58; 95% confidence interval (CI), 0.54–0.63 to 0.97;0.94–0.99, of having HbA1c ≤7% (adjusted for covariates). Patients on insulin‐based treatments had the lowest likelihood, while non‐pharmacological treatment was associated with an increased likelihood of having HbA1c ≤7%. Conclusion: This nation‐wide study shows insufficiently reached treatment goals for haemoglobin A1c (HbA1c) in all treatment groups. Patients on insulin‐based treatment regimens had the longest duration of diabetes, more cardiovascular risk factors and the highest proportions of patients not reaching HbA1c target.     

The effect of obesity on glycaemic response to metformin or sulphonylureas in Type 2 diabetes.

Aims In treating Type 2 diabetes (T2DM), UK guidelines recommend metformin in obese and overweight patients, and either sulphonylureas or metformin in normal weight patients. Although other factors influence prescribing choice, a key objective in treating T2DM is to lower plasma glucose. There is little data on how glycaemic response to oral agents varies with body mass index (BMI). Therefore, we assessed current prescribing practice and effect of BMI on glycaemic response to sulphonylureas and metformin in a large population T2DM cohort. Methods BMI was determined in 3856 T2DM patients on sulphonylurea or metformin monotherapy in 2001–2002. Patients were identified from the Diabetes Audit and Research in Tayside, Scotland (DARTS) database. In a linear regression, the effect of BMI and other confounders on drug response was assessed in 2064 treatment‐naïve patients commencing sulphonylureas or metformin between 1994 and 2002. Results In 2001–2002, metformin was more likely to be used in obese than non‐obese patients: 13% normal weight, 33.6% overweight and 62.1% obese patients were treated with metformin. Glycaemic response to sulphonylureas was not influenced by BMI (P = 0.81). Metformin was more effective in lowering glucose in those with a lower BMI (r = –0.02, P = 0.02), although the clinical impact of this was small. The HbA_1c reduction in non‐obese patients was similar to that in obese patients (1.46% vs. 1.34%, P = 0.11). Conclusions Glycaemic response to metformin in non‐obese and obese patients is similar, suggesting that an individual's BMI should not influence the choice of oral agent. Given the non‐glycaemia‐related benefits of metformin, it should be used in more non‐obese patients than is current practice in Tayside, Scotland.     

Comparison of alogliptin and glipizide for composite endpoint of glycated haemoglobin reduction,no hypoglycaemia and no weight gain in type 2 diabetes mellitus

This was a post hoc analysis of a 2‐year, double‐blind study of 2639 patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin monotherapy, which assessed achievement of a composite endpoint of sustained glycated haemoglobin (HbA1c) reduction (≤7.0% at week 104 or ≥0.5% decrease from baseline) with no weight gain and no hypoglycaemic events with alogliptin 12.5 and 25 mg daily or glipizide (≤20 mg daily), each added to metformin. With an HbA1c target of ≤7.0%, 24.2 and 26.9% of patients treated with alogliptin 12.5 and 25 mg, respectively, achieved the composite endpoint versus 10.7% of patients treated with glipizide (both p < 0.001). With a criterion of ≥0.5% decrease in HbA1c, the composite endpoint was reached in 22.5, 25.2 and 10.4% of patients treated with alogliptin 12.5 mg, alogliptin 25 mg and glipizide, respectively. Odds ratios for achieving the composite endpoint favoured alogliptin in the primary analysis set and in all subgroups of patients. Patients with T2DM failing metformin monotherapy were more likely to achieve sustained glycaemic control with no hypoglycaemia or weight gain at 2 years with alogliptin than with glipizide.     

Nateglinide, alone or in combination with metformin, is effective and well tolerated in treatment-naïve elderly patients with type 2 diabetes

Aim: The aim of this work was to assess the efficacy and tolerability of nateglinide alone or in combination with metformin in elderly patients with type 2 diabetes (T2DM). Methods: Study 1 was a 12‐week, multicentre, randomized, double blind and placebo‐controlled study of nateglinide monotherapy (120 mg, before meals) in 66 drug‐naïve patients with T2DM aged ≥65 years. Study 2 was a 104‐week, multicentre, randomized, double blind and active‐controlled study of nateglinide (120 mg, before meals) or glyburide (up to 5 mg bid) in combination with metformin (up to 1000 mg bid) in 69 treatment‐naïve patients with T2DM aged ≥65 years. HbA_1c, fasting and postprandial glucose levels, and safety assessments were made. Results: In Study 1, nateglinide significantly reduced HbA_1c from baseline (7.6 ± 0.1% to 6.9 ± 0.1%; Δ = ?0.7 ± 0.1%, p < 0.001) and compared with placebo (between‐group difference = ?0.5%, p = 0.004 vs. nateglinide). No hypoglycaemia was reported. In Study 2, combination therapy with nateglinide/metformin significantly reduced HbA_1c from baseline (7.8 ± 0.2% to 6.6 ± 0.1%; Δ = ?1.2 ± 0.2%, p < 0.001), as did glyburide/metformin (7.7 ± 0.1% to 6.5 ± 0.1%; Δ = ?1.2 ± 0.1%, p < 0.001). There was no difference between treatments (p = 0.310). One nateglinide/metformin‐treated patient experienced a mild hypoglycaemic episode compared with eight episodes in eight patients on glyburide/metformin; one severe episode led to discontinuation. Target HbA_1c (<7.0%) was achieved by 60% of patients receiving nateglinide (Study 1) and 70% of nateglinide/metformin‐treated patients (Study 2). Conclusion: Initial drug treatment with nateglinide, alone or in combination with metformin, is well tolerated and produces clinically meaningful improvements in glycaemic control in elderly patients with T2DM.