格列吡嗪控释片治疗2型糖尿病疗效和安全性观察

目的 :观察磺脲类药物格列吡嗪控释片 (瑞易宁 )治疗 2型糖尿病的有效性和安全性。方法 :选择无磺脲类药物继发失效的 2型糖尿病患者 97例 ,随机分入格列吡嗪控释片组 (观察组 )和格列苯脲组 (对照组 ) ,观察时间为 16wk(剂量调整期 8wk,维持期 8wk)。结果 :观察组降糖的有效率为 89 79% ,对照组为 89 5 8% ,两组间比较差异无显著意义 (X2 =0 0 0 0 2 ,P >0 0 5 )。治疗16wk后空腹血糖 (FBG)、餐后 2h血糖 ( 2hPBG)、糖化血红蛋白 (HbA1c)显著降低 (P <0 0 5 ) ,但两组比较差异无显著意义 (P >0 0 5 )。 2hPBG和C肽水平观察组低于对照组 (P <0 0 5 ) ,但FBG及C肽水平两组相似 (P >0 0 5 )。格列吡嗪控释片对肝、肾功能和血压无不良反应。观察组低血糖的发生率 [6 12 % ( 3 4 9) ]与对照组比较 [2 6 % ( 13 5 0 ) ],差异有显著意义 (X2 =7 4 14 ,P <0 0 1)。结论 :格列吡嗪控释片治疗 2型糖尿病疗效可靠、安全、顺应性好     

格列吡嗪控释片对磺脲类药物疗效不佳的2型糖尿病患者的疗效观察

目的:评价口服磺脲类降糖药物效果不佳改用格列吡嗪控释片或加用睡前中效胰岛素治疗对糖尿病患者的治疗效果。方法:142例口服磺脲类药物治疗的2型糖尿病患者随机分为4组:A组原磺脲类治疗组;B组改用格列吡嗪控释片治疗组;C组格列吡嗪控释片加睡前胰岛素组;D组原磺脲类加睡前胰岛素组。治疗12周后观察血糖、胰岛素水平和糖化血红蛋白的改变。结果:在4组中,格列吡嗪控释片加胰岛素组和磺脲类降糖药物加胰岛素组治疗效果最好,改用格列吡嗪控释片血糖较原治疗组有所改善,糖化血红蛋白降低,而维持原磺脲类治疗组效果不理想。格列吡嗪控释片加胰岛素组服药依从性好,不良反应少,低血糖发生率低。结论:对于原磺脲类药物治疗不达标患者,换用格列吡嗪控释片治疗具有较好的服药依从性和满意度,治疗效果优于换药前,且可以降低糖化血红蛋白水平,值得临床推广。加用胰岛素睡前注射治疗可更好地控制血糖(包括空腹和餐后血糖),降低胰岛素和糖化血红蛋白水平,但低血糖发生率增多,在临床应用中应加以注意。     

格列吡嗪控释片对2型糖尿病病人血清胰岛素样生长因子的影响

目的 :探讨格列吡嗪控释片对 2型糖尿病病人血糖、胰岛素及胰岛素样生长因子Ⅰ ,Ⅱ (IGF Ⅰ ,Ⅱ )的影响。方法 :糖尿病组初次诊断的 2型糖尿病病人 6 8例 ,对照组健康体检者 4 3例。糖尿病组予格列吡嗪控释片 5～ 10mg ,每日 1次 ,早餐前服用 ,疗程 4wk。观察治疗前后空腹血糖 (FBG)、糖化血红蛋白 (HbA1c)、空腹胰岛素 (FINS)、IGF Ⅰ和IGF Ⅱ的情况。结果 :与对照组比 ,糖尿病组治疗前FINS ,IGF Ⅰ ,IGF Ⅱ水平较低 ,FBG和HbA1c水平较高 (均P <0 .0 1)。治疗后 ,FBG和HbA1c下降 ,FINS ,IGF Ⅰ ,IGF Ⅱ升高 (P <0 .0 1)。结论 :每日服用 1次格列吡嗪控释片可以改善 2型糖尿病病人的糖代谢及血清IGF Ⅰ和IGF Ⅱ的水平。     

格列吡嗪控释片治疗2型糖尿病开放性非对照性临床试验

90年代开发成功的格列吡嗪控释片是目前唯一采用胃肠道治疗系统技术制备的新型磺脲类降糖药。它仅需每日一次就能提供 2 4小时强化血糖控制和生理性胰岛素反应 ,同时又保持格列吡嗪良好的安全性。 1994年经美国 FDA批准先后在美国、欧洲乃至全球上市 ,成为治疗 2型糖尿病的一线药物。本文通过观察格列吡嗪控释片在我院临床应用治疗 2型糖尿病患者 ,评价其安全性和疗效。1　对象及方法1.1　对象 :新诊断为 2型糖尿病或已诊断但未经固定药物治疗者 (A组 ,10例 ) ;正在接受磺脲类药物治疗 (可同时合并使用其它类型的口服降糖药 )且药物品种剂…     

格列吡嗪控释片治疗II型糖尿病的临床疗效评价

目的 :对比研究格列吡嗪控释片与格列吡嗪速释片对Ⅱ型糖尿病的疗效。方法 :选择 80例Ⅱ型糖尿病患者 ,给予格列吡嗪控释片 (n =5 0 )和格列吡嗪速释片 (n =3 0 )治疗 ,观察两组治疗前后血糖和胰岛素的变化。结果 :格列吡嗪控释片每日一次服用的降糖效果与格列吡嗪速释片每日 2～ 3次服用效果相同 ;后者治疗后空腹和餐后胰岛素较前者明显升高。结论 :格列吡嗪控释片有较好的降糖效果 ,同时不引起高胰岛素血症     

格列吡嗪控释片治疗2型糖尿病的临床疗效及安全性

目的探讨格列吡嗪控释片治疗2型糖尿病的临床疗效及安全性。方法选择2型糖尿病患者262例,随机分为2组,治疗组132例采用格列吡嗪控释片治疗,对照组130例采用格列吡嗪片治疗,比较2组的治疗效果和安全性。结果治疗组有效率明显高于对照组,差异有统计学意义(P<0.05)。对照组有5例患者出现血糖低,治疗组未发现。结论格列吡嗪控释片24 h内可保持较稳定的血药浓度,还能刺激B细胞按需释放胰岛素,服药依从性高,副反应少。     

参芪降糖颗粒联合胰岛素对磺脲类降糖药物继发性失效的2型糖尿病患者糖脂代谢及低血糖发作的影响

目的:观察参芪降糖颗粒联合胰岛素对磺脲类降糖药物继发性失效的2型糖尿病患者糖脂代谢及低血糖发作的影响。方法:将128例磺脲类降糖药继发性失效的2型糖尿病患者随机均分为观察组和对照组。所有患者均停用原来使用的降糖药物。对照组患者给予胰岛素泵以每日0.3单位/kg为起始剂量,后根据患者血糖水平每3~5 d调整1次胰岛素剂量;观察组患者在对照组治疗的基础上加用参芪降糖颗粒2 g,口服,tid。两组患者疗程均为2个月。观察两组患者治疗前后餐后2 h血糖(2 h PG)、空腹血糖(FPG)、糖化血红蛋白(Hb A1c)、平均血糖波动度(MAGE)、空腹胰岛素(FINS)、胰岛素敏感指数(ISI)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、低血糖发作情况,并记录不良反应发生情况。结果:治疗后,两组患者2 h PG、FPG、Hb A1c、MAGE、FINS均显著低于同组治疗前,且观察组低于对照组;观察组患者ISI显著高于同组治疗前及对照组,差异均有统计学意义(P<0.05);观察组患者TC、TG、LDL-C均显著低于同组治疗前及对照组,HDL-C显著高于同组治疗前及对照组(P<0.05);对照组患者ISI、TC、TG、LDL-C、HDL-C治疗前后比较差异均无统计学意义(P>0.05)。观察组患者低血糖发生率显著低于对照组(P<0.05)。两组患者治疗期间均未见明显不良反应发生。结论:参芪降糖颗粒联合胰岛素可显著改善磺脲类降糖药继发性失效的2型糖尿病患者的血脂水平,有效控制血糖、减少低血糖发作,安全性较好。     

格列吡嗪控释片治疗Ⅱ型糖尿病的临床疗效评价

目的：对比研究格列吡嗪控释片与格列吡嗪速释片对Ⅱ型糖尿病的疗效。方法：选择80例Ⅱ型糖尿病患，给予格列吡嗪控释片（n=50）和格列吡嗪速释片（n=30）治疗，观察两组治疗前后血糖和胰岛素的变化。结果：格列吡嗪控释片每日一次服用的降糖效果与格列吡嗪速释片每日2－3次服用效果相同。后治疗后空腹和餐后胰岛素较前明显升高。结论：格列吡嗪控释片有较好的降糖效果，同时不引起高胰岛素血症。     

格列吡嗪控释片对2型糖尿病患者血糖控制的临床效果

目的探讨格列吡嗪控释片对2型糖尿病患者血糖控制的临床意义。方法参照WHO诊断标准,选择2011年1月至2013年1月在我院诊治的2型糖尿病患者1 042例。在早餐前立即服用格列吡嗪控释片(5 mg/片,瑞易宁),服药12周。在服用前后,测定患者的肝、肾功、血压、2hPG、FPG、HbA1c、C肽、胰岛素水平、ISI。根据血糖测定的结果调整服用药物的剂量,每2周1次;若FPG>7.0 mmol/L,增加服药剂量,增加5 mg/次,最大剂量为10 mg/d。结果给药后,患者的FPG、2hPG、HbA1c、C肽与胰岛素均降低,ISI显著升高,与治疗前比较差异有统计学意义(P<0.05)。结论格列吡嗪控释片对2型糖尿病患者血糖控制疗效显著,具有重要的临床价值。     

格列吡嗪控释片治疗2型糖尿病临床疗效观察

目的探讨研究并且进行仔细认真的比较使用速释片和格列吡嗪控释片治疗2型糖尿病所发生的一些不良反应以及对其血糖控制效果。方法将128例患有2型糖尿病患者随机分为速释片组以及格列吡嗪控释片组,其中素释片组67例,格列吡嗪控释片组61例,细心观察治疗14周后的胰岛素、血糖和C肽水平的状况、两组的药物不良反应情况以及所使用的维持剂量。结果两组治疗后空腹血糖和餐后2h血糖全部都有降低的趋势,控释片组的降空腹血糖效果要比速释片组体现的更为显著（P〈0．05）;控释片组的维持剂量较小;两组不良反应发生率近乎相同。糖化血红蛋白治疗后均有下降,但组间比较差别不是很大;空腹胰岛素及c肽治疗前后两组均没有显著的不同。结论格列吡嗪控释片能够充分的发挥与速释片有所相同的治疗效果,其降空腹血糖效果相比会更好。     

格列吡嗪控释片与格列吡嗪片（迪沙片）治疗2型糖尿病的疗效观察

目的：比较格列吡嗪控释片和格列吡嗪片治疗2型糖尿病的疗效差异。方法：将单纯饮食控制或加用盐酸二甲双胍药物治疗不满意的2型糖尿病患者56例,随机分成格列吡嗪控释片组28例和格列吡嗪片组28例,疗程12周。监测两组治疗前及治疗后的空腹及餐后2 h血糖,治疗前及治疗后12周糖化血红蛋白（HbA1c）的变化及患者服药的依从性等。并观察有否低血糖等不良反应。结果：用格列吡嗪控释片和格列吡嗪片治疗后空腹血糖都有明显下降（P〈0.05）,格列吡嗪控释片对餐后2 h血糖的疗效高于格列吡嗪片,但差异无统计学意义（P〉0.05）。结论：格列吡嗪控释片和格列吡嗪片使空腹血糖都有明显下降,但格列吡嗪控释片控制餐后高血糖和HbA1c要优于格列吡嗪片,且服用格列吡嗪控释片依从性优于格列吡嗪片。     

Glipizide. A review of the pharmacoeconomic implications of the extended-release formulation in type 2 diabetes mellitus

Glipizide is a second generation sulphonylurea agent that is available in a Gastrointestinal Therapeutic System (GITS) extended-release formulation. Glipizide GITS provides more stable plasma drug concentrations than the immediate-release formulation and the once-daily regimen may optimise patient compliance. In patients with type 2 diabetes mellitus, glipizide GITS is at least as effective as the immediate-release formulation of glipizide in providing glycaemic control, and may have a greater effect on fasting plasma glucose levels. Any therapeutic advantage over other antidiabetic agents remains to be established, but in a preliminary report (n = 40) glipizide GITS provided better glycaemic control and produced less fasting insulinaemia than glibenclamide (glyburide). The incidence of hypoglycaemic symptoms with glipizide GITS is low (< or = 3%). Quality of life was improved compared with baseline after 12 weeks' treatment with glipizide GITS 5 to 20 mg/day plus diet in a US double-blind, placebo-controlled trial in 569 patients with type 2 diabetes mellitus. Hyperglycaemic symptom-related distress decreased with glipizide GITS treatment, while hypoglycaemic symptom-related distress was not significantly increased compared with placebo plus diet. Quality of life during glipizide GITS treatment has not been compared with that during treatment with other antidiabetic agents. Monthly productivity losses related to absenteeism were $US91 (1995 values) per patient lower in the glipizide GITS group compared with the placebo group in the latter prospective study. Productivity parameters improved slightly or did not change significantly in the glipizide GITS group, but deteriorated in the placebo group. Differences in direct healthcare costs between groups were small and not comprehensively reported. Glipizide GITS was the least costly strategy for first-line therapy in a US cost-of-treatment model of the first 3 years after diagnosis of type 2 diabetes mellitus. The total per-patient cost was $US4867 with glipizide GITS, $US5196 with metformin and $US5249 with acarbose (1996/1997 values). Monthly drug acquisition costs were lower, and glycosylated haemoglobin levels and patient compliance were improved, after formulary conversion from the immediate-release to the GITS formulation of glipizide in a US single-hospital retrospective analysis. CONCLUSIONS: Glipizide GITS produced better cost outcomes than metformin and acarbose in a model of 3 years' treatment of type 2 diabetes mellitus. Glipizide GITS had pharmacoeconomic and quality of life advantages over diet alone in the short term, but more clinically relevant comparisons with other antidiabetic agents are needed. There are limitations to the present data, but the available pharmacoeconomic data have been favourable for glipizide GITS.     

Effect of glipizide GITS on insulin sensitivity,glycemic indices,and abdominal fat composition in NIDDM

Glipizide in a once daily formulation utilizing the gastrointestinal therapeutic system (GITS) has been shown in preliminary studies to improve insulin sensitivity as assessed with meal tolerance testing. To evaluate the ability of glipizide GITS to specifically improve clinical insulin sensitivity in vivo, a double–blind, placebo-controlled trial randomized 40 NIDDM subjects to either glipizide GITS or placebo. The study was designed to evaluate NIDDM subjects whose fasting blood glucose was <190 mg% and Ghb <11% to avoid the adverse effects of hyperglycemia on insulin resistance and secretion. After screening, oral hypoglycemic agents were discontinued for one month, at which time a meal tolerance test with glucose and insulin response, glycated hemoglobin, and fructosamine were obtained. Insulin sensitivity (S_I) and glucose effectiveness (S_g) were determined with a 4–h frequently sampled intravenous tolerance test (modified minimal model – 3rd phase insulin infusion) at baseline. Specific abdominal fat depots were quantitated by MRI scans. Patients were then randomized to receive placebo or active drug and all parameters were repeated at 1, 2, 5, and 8 months after randomization. Glipizide GITS significantly improved meal tolerance, reduced glycated blood proteins, and increased insulin sensitivity (P < .001). No change was seen for S_G. There was no significant change in abdominal fat distribution during the trial. Glipizide GITS is effective in lowering glucose tolerance and improving insulin sensitivity without an increase in fasting insulin, weight gain, or change in abdominal fat composition. Drug Dev. Res. 44:1–7, 1998. © 1998 Wiley-Liss, Inc.     

随机、开放、低精蛋白锌胰岛素注射液平行对照,联合控释格列吡嗪评价重组甘精胰岛素注射液治疗口服降糖药控制不佳的2型糖尿病患者的有效性和安全性

目的:评价甘精胰岛素与控释格列吡嗪(瑞易宁)联合应用治疗2型糖尿病患者的有效性和安全性。方法:采用随机、开放、低精蛋白锌胰岛素注射液(诺和灵N)平行对照和多中心临床研究方法,对471例服用口服降糖药(OHA)至少3个月而血糖控制不佳(FBG≥7.0mmol_L)的2型糖尿病患者随机进行试验药-甘精胰岛素或对照药-诺和灵N治疗,随访5次共12周。结果:治疗12周时,甘精胰岛素组与诺和灵N组的胰岛素平均每天用量分别为19.21单位和18.68单位,平均空腹血糖分别从入选时10.63mmol_L和10.88mmol_L降至6.96mmol_L和7.20mmol_L,HbA1c分别下降了0.96%和1.25%。甘精胰岛素组和诺和灵N组分别有21.25%(75_353)和28.81%(34_118)的受试者发生低血糖(P=0.0919),其中发生夜间低血糖的受试者分别占9.07%(32_353)和16.10%(19_118)(P=0.0334)。以低血糖的发生例次作为观察指标时,甘精胰岛素组和诺和灵N组分别有174例次和75例次,其中夜间低血糖分别有54例次和44例次,两组均没有严重低血糖事件。结论:12周的临床观察显示,睡前注射一次甘精胰岛素和清晨口服5mg瑞易宁联合应用的治疗方法可使单纯使用口服降糖药而代谢控制不佳的2型糖尿病患者得到良好的血糖控制;以HbA1c和空腹血糖水平作为判断指标,甘精胰岛素和诺和灵N分别与瑞易宁联合应用两种治疗方法对2型糖尿病患者治疗效果相当,但前者夜间低血糖事件发生率低;同时,甘精胰岛素(睡前1次)与瑞易宁联合应用的治疗方法具有良好的耐受性。     

Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of type 2 diabetes mellitus: In vitro and in vivo evaluation

Type 2 diabetes mellitus is a heterogeneous disease of polygenic origin and involves both defective insulin secretion and peripheral insulin resistance. Studies have shown that post-meal hyperglycemic spikes are associated with increased cardiovascular mortality in type 2 diabetes. Over the past decade, a major interest in control of postprandial glucose excursion has emerged and a plethora of new medications that specifically target postprandial hyperglycemia were discovered. Despite the availability of new agents for treatment of type 2 diabetes mellitus, oral sulfonylureas remain a cornerstone of therapy, because they are relatively inexpensive and are well tolerated. However, hypoglycemia is a major safety concern with sulfonylureas and it is one major risk factor requiring hospitalization. Glipizide is a potent, rapid-acting with short duration of action and well tolerated second-generation sulfonylurea effective in reducing postprandial glucose levels. However, risk of postprandial hypoglycemia and post-meal glucose excursions, if dose missed before meal; are always associated with the use of glipizide for treatment of type 2 diabetes mellitus. Since, the site of absorption of glipizide is from stomach thus dosage forms that are retained in stomach by mucoadhesion; would increase absorption, improve drug efficiency and decrease dose requirements. Microsphere carrier systems made by using polymer galactomannan having strong mucoadhesive properties and easily biodegradable could be an attractive strategy to formulate. The purpose of this research work is to formulate galactomannan coated mucoadhesive microspheres of glipizide and systematically evaluate its in vitro characteristics and in vivo performance for sustained glucose lowering effect and improvement in diabetic condition as compared to immediate release of glipizide.     

Glipizide: a second-generation sulfonylurea hypoglycemic agent. Pharmacology, pharmacokinetics and clinical use

Glipizide is a second-generation sulfonylurea in which the substitutions on the arylsulfonylurea nucleus are large, relatively nonpolar groups. This chemical change increases the intrinsic hypoglycemic activity of the molecule 100-fold on a weight basis compared to first-generation agents. In addition, the pharmacokinetic properties, spectrum and severity of side effects and metabolism of this agent are somewhat different from those of first-generation sulfonylureas. The most important component of the antidiabetic action of glipizide is its effect in potentiating insulin action. Glipizide-mediated increases in nutrient-stimulated insulin secretion may contribute to its antidiabetic action. The drug is effective in controlling the blood glucose in patients with noninsulin-dependent diabetes mellitus. It is at least as effective as and probably more effective than first-generation sulfonylureas in controlling hyperglycemia in diabetes. Glipizide is relatively free of serious side effects and is contraindicated principally in patients with significant liver or kidney disease.     

Pharmacokinetics and pharmacodynamics of extended-release glipizide GITS compared with immediate-release glipizide in patients with type II diabetes mellitus

This study was designed to compare the pharmacokinetic and short-term pharmacodynamic profile of extended-release glipizide GITS (Glucotrol XL) given in a dosage of 20 mg once daily with that of immediate-release glipizide (Glucotrol) 10mg twice daily in patients with type II diabetes mellitus. In an open-label, randomized, two-way crossover study, each glipizide formulation was administered for 5 days. Serial blood samples were drawn at baseline and on the 5th day of each treatment phase for measurement of glipizide, glucose, insulin, and C-peptide concentrations. At steady state, the mean Cmax after immediate-release glipizide was significantly greater than after glipizide GITS, and the tmax was considerably shorter. Although the mean Cmin with glipizide GITS was about 80% higher than with immediate-release glipizide, the mean AUC0-24 was significantly lower. Despite the lower plasma concentrations with glipizide GITS in this short-term study, the two formulations had similar effects on serum concentrations of glucose, insulin, and C-peptide. The absence of a pronounced peak plasma concentration with the GITS formulation might confer advantages in terms of maintaining clinical effectiveness and reducing the potential to cause adverse effects.     

Plasma levels of glucose and lactate after intravenous cadministration in some insulin-dependent diabetics. Therapeutic effects of an associated glipizide-insulin treatment

Summary

A study was carried out to evaluate the effectiveness of glipizide in insulin-dependent diabetic patients. An intravenous glipizide (2?mg)test was carried out in 7 patients before and after a period of associated insulin-glipizide treatment (mean daily dose of 80.7 i.v. lente insulin and 14.3?mg glipizide for 9.1 months)to assess the capacity of the sulphonylurea to reduce acutely the plasma glucose and lactate levels. Glipizide did not produce glucose variations in either test but did result in a significant decrease, in the first test only, in mean plasma baseline levels of lactate, which were higher than normal in these patients. There was no reduction in daily insulin requirements after the period of associated glipizide-insulin treatment. It is concluded that, in the dosage used, intravenous glipizide probably has no hypoglycaemic effects in insulin-dependent diabetics. Moreover, it did not prove useful in combination with insulin. However, the reduction in plasma lactate may be related to an acute enhancement of the exogenously administered insulin. This improvement in the insulin effect may be an acute one among the so-called ‘extra-pancreatic’ actions which have been demonstrated for glipizide and other sulphonylureas.     

Plasma levels of glucose and lactate after intravenous glipizide administration in some insulin-dependent diabetics. Therapeutic effects of an associated glipizide-insulin treatment.

A study was carried out to evaluate the effectiveness of glipizide in insulin-dependent diabetic patients. An intravenous glipizide (2 mg) test was carried out in 7 patients before and after a period of associated insulin-glipizide treatment (mean daily dose of 80.7 i.v. lente insulin and 14.3 mg glipizide for 9.1 months) to assess the capacity of the sulphonylurea to reduce acutely the plasma glucose and lactate levels. Glipizide did not produce glucose variations in either test but did result in a significant decrease, in the first test only, in mean plasma baseline levels of lactate, which were higher than normal in these patients. There was no reduction in daily insulin requirements after the period of associated glipizide-insulin treatment. It is concluded that, in the dosage used, intravenous glipizide probably has no hypoglycaemic effects in insulin-dependent diabetics. Moreover, it did not prove useful in combination with insulin. However, the reduction in plasma lactate may be related to an acute enhancement of the exogenously administered insulin. This improvement in the insulin effect may be an acute one among the so called "extra-pancreatic" actions which have been demonstrated for glipizide and other sulphonylureas.