格列齐特治疗非胰岛素依赖型糖尿病

观察６０例Ⅱ型糖尿病病人服用格列齐特的国产与法国产２种制剂的近期疗效。结果：两者对Ⅱ型糖尿病均有明显降血糖作用，不良反应轻微，在其他磺酰脲类药物治疗无效时，格列齐特仍可有明显疗效。无论是２组组间比较还是自身对照比较，两者的降糖作用，有效剂量，维持剂量和疗效反应都十分相近。     

Is gliclazide a sulfonylurea with difference? A review in 2016

Sulfonylureas (SUs) remain the most commonly prescribed drug after metformin in the treatment of type 2 diabetes (T2DM), despite the availability of several newer agents. The primary reason of SUs being most popular is their quick glycemic response, time-tested experience and least cost. Although SUs are one amongst the several other second line agents after metformin in all major guidelines, the new Dutch type 2 guidelines specifically advise gliclazide as the preferred second line drug instead of SUs as a class. The World Health Organization (WHO) has also included gliclazide in their Model List of Essential Medicines 2013 motivated by its safety data in elderly patients. Specifically advising gliclazide may have been based on emerging evidence suggesting cardiovascular neutrality of gliclazide over other SUs. This prompted us to do a literature review of gliclazide efficacy and safety data compared to other SUs as well as oral anti-diabetic drugs.     

The efficacy of self-monitoring of blood glucose in the management of patients with type 2 diabetes treated with a gliclazide modified release-based regimen. A multicentre, randomized, parallel-group, 6-month evaluation (DINAMIC 1 study)

Aim: To determine if therapeutic management programmes for type 2 diabetes that include self‐monitoring of blood glucose (SMBG) result in greater reductions in glycated haemoglobin (HbA1c) compared with programmes without SMBG in non‐insulin requiring patients. Methods: Multicentre, randomized, parallel‐group trial. A total of 610 patients were randomized to SMBG or non‐SMBG groups. Patients in both groups received the same oral antidiabetic therapy using a gliclazide modified release (MR)–based regimen for 27 weeks. The primary efficacy end‐point was the difference between groups in HbA1c at the end of observation. Results: A total of 610 patients were randomized: 311 to the SMBG group and 299 to the non‐SMBG group. HbA1c decreased from 8.12 to 6.95% in the SMBG group and from 8.12 to 7.20% in the non‐SMBG group; between‐group difference was 0.25% (95% CI: 0.06, 1.03; p = 0.0097). Symptoms suggestive of mild to moderate hypoglycaemia was the most commonly reported adverse event, reported by 27 (8.7%) and 21 (7.0%) patients in the SMBG and non‐SMBG groups, respectively; the incidence of symptomatic hypoglycaemia was lower in the SMBG group. Conclusion: In patients with type 2 diabetes, the application of SMBG as an adjunct to oral antidiabetic agent therapy results in further reductions in HbA1c.     

Reversible binding of antidiabetic drugs, repaglinide and gliclazide, with human serum albumin

Mechanism of interaction of antidiabetic drugs, repaglinide and gliclazide, to human serum albumin has been studied using fluorescence spectroscopic technique. Repaglinide had much higher affinity for human serum albumin when compared with gliclazide. The order of association constants was 10(5) for both the drugs. The size, hydrophobicity and flexibility of the drug molecules play a major role in explaining the binding behaviour of these drugs. Hydrophobic interactions are predominantly involved in the binding. However, drugs do not share common sites with 1-anilinonaphthalene-8-sulphonate on the human serum albumin molecule. Both tyrosine and tryptophan residues participate in the interaction. Repaglinide and gliclazide are bound to site II on the human serum albumin molecule, and the aromatic ring of 411Tyr appears to be involved in binding within site II. Although they do not bind at site I, their binding at site II may cause conformational changes thereby affecting the binding of other ligands to site I. Site-specificity can be useful in predicting the competitive displacement of these drugs by other co-administered drugs, resulting in fluctuations of the blood glucose levels in diabetic patients. Stern-Volmer analysis of quenching data indicated that the tryptophan residues are not fully accessible to the drugs and predominantly dynamic quenching mechanism is involved in the binding.     

基于实心核颗粒色谱技术结合HPLC法快速测定保健食品中非法添加13种降糖化学成分

目的建立保健食品中非法添加13种降糖性化学成分(甲苯磺丁脲、格列本脲、格列齐特、格列吡嗪、格列喹酮、格列美脲、马来酸罗格列酮、瑞格列奈、盐酸吡格列酮、盐酸二甲双胍、盐酸苯乙双胍、盐酸丁二胍、格列波脲)的HPLC快速检测方法。方法以高色谱性能的实心核颗粒色谱柱CORTECS-C18(100 mm×4.6 mm,2.7μm)快速分离,二极管阵列检测器(PDA)检测,进行定性定量检测分析,样品以甲醇为溶剂超声提取,在10 min内同时检测添加在保健食品中的甲苯磺丁脲、格列本脲、格列齐特、格列吡嗪、格列喹酮、格列美脲、马来酸罗格列酮、瑞格列奈、盐酸吡格列酮、盐酸二甲双胍、盐酸苯乙双胍、盐酸丁二胍、格列波脲13种化学成分。结果 13种降糖化学成分色谱检测的分离度好,线性范围宽,相关性好,r2≥0.998 7;方法精密度以6次测定值的RSD表示,为0.6%~1.5%;方法回收率用3个质量浓度进行添加实验,回收率为95.9%~104.7%;定量限为1.1~3.3μg/m L;日间精密度的RSD为0.5%~1.6%(n=9)。86批降糖类保健食品中检出17批添加化学药,检出率为20%;样品中检出了格列本脲、盐酸苯乙双胍、马来酸罗格列酮、格列美脲、盐酸二甲双胍、盐酸吡格列酮。结论本方法通用性强,操作简单、快捷,可作为保健食品中非法添加13种降糖化学成分的有效检测方法。     

Dynamics of insulin release and microtubular-microfilamentous system. V. A model for the phasic release of insulin

Abstract. A model is proposed to account for the phasic nature of insulin release. It is suggested that one modality of secretion results from the mobilization of secretory granules already located in the close vicinity of the microfilamentous cell web. This corresponds to a fraction of the initial secretory response to a high glucose concentration, the residual release of insulin provoked by glucose in the presence of diazoxide, and the total release of insulin evoked by sulphonylurea at a low glucose concentration. A second modality of release, which is characteristic of the late phase of glucose-induced insulin secretion, is thought to correspond to the mobilization of secretory granules transported to the periphery of the β-cell along oriented microtubular pathways. Whether only one or both modalities of release are initiated by a given insulinotropic stimulus may depend on the magnitude and duration of the changes induced by secretagogues in the insular handling of calcium.     

Antioxidant effects of gliclazide, glibenclamide, and metformin in patients with type 2 diabetes mellitus

Background: Hyperglycemia increases oxygen-reactive species generation and reduces the protective capabilities of antioxidant defense systems. In patients with type 1 or 2 diabetes mellitus (DM), the increased production of oxygen free radicals may be linked to the development of chronic complications of diabetes. In vitro studies have demonstrated that oral antidiabetic drugs have antioxidant effects that might be secondary to an inhibiting role in lipid peroxidation.Objective: The purpose of this study was to determine the effects of 3 common oral antidiabetic agents on oxidized anti-low-density lipoprotein antibody (o-LAb) plasma levels and on total antioxidant status (TAS).Methods: We studied in vivo patients with type 2 DM treated with long-term gliclazide, glibenclamide, or metformin therapy along with healthy control subjects. The diabetic patients were randomized to the following treatment groups: group 1, gliclazide 80 to 240 mg/d; group 2, glibenclamide 10 to 15 mg/d; and group 3, metformin 1500 mg/d.Results: Ninety-two patients with type 2 DM (group 1, 18 females, 15 males [mean age, 62.8 ± 9.5 years]; group 2, 19 females, 11 males [mean age, 63.2 ± 8.8 years]; group 3, 16 females, 13 males [mean age, 62.0 ± 5.3 years]) and 28 age- and sex-matched healthy control subjects (18 females, 10 males; mean age, 59.1 ± 5.3 years) were enrolled. In group 1, both the o-LAb level and TAS were similar to those of the control group. The o-LAb level was highest and the total antioxidant plasma level was lowest in group 3, whereas intermediate levels were found in group 2. Multivariate analysis using stepwise regression showed that the type of oral antidiabetic agent was independently associated with o-LAb and total antioxidant levels, as well as with sex, age, and type of antidiabetic agent.Conclusion: In the patients with type 2 DM in this study, gliclazide had a positive effect on the oxidation-reduction system.     

格列齐特缓释片处方及工艺研究

目的筛选格列齐特缓释片的处方及工艺。方法以体外释放度为考察指标,优选格列齐特缓释片的骨架材料、填充剂、释放速率调节剂、黏合剂等。结果确定了以羧甲基纤维素钠(CMC-Na)(低黏度CMC-Na 52 mg、高黏度CMC-Na 32 mg)作为基本骨架材料,磷酸氢钙(150 mg)作为填充剂,糊精(22 mg)作为释放速率调节剂,85%乙醇为黏合剂,硬脂酸镁、微粉硅胶为润滑剂和助流剂的处方。制备的格列齐特缓释片释放行为与参比制剂基本相似。结论优选的处方合理、工艺稳定、可行,且大大降低了生产成本。     

Management of high blood pressure in type 2 diabetes: perindopril/indapamide fixed-dose combination and the ADVANCE trial

Importance of the field: The increase in type 2 diabetes mellitus is associated to cardiovascular morbidity and mortality. This review focuses on the benefits of the fixed-dose combination of perindopril and indapamide on cardiovascular and renal end points in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) trial.

Areas covered in the review: In the last decade, clinical trials have indicated that blood pressure reduction and glucose lowering were effective in reducing morbidity and morbility. The ADVANCE trial has explored both intensive glucose lowering with gliclazide modified release (MR) and intensive blood pressure lowering using a fixed combination of perindopril/indapamide, on top of current treatments, including renin-angiotensin inhibitors.

What the reader will gain: In ADVANCE, perindopril/indapamide reduced a composite of macrovascular and microvascular events, also significantly decreasing cardiovascular mortality and death from any cause and reducing coronary and renal complications. The review discusses the relevance of results and the advantages of this therapeutic strategy in clinical practice.

Take home message: ADVANCE provides a new, simple and pragmatic treatment algorithm that maximizes clinical benefits and is suitable for all type 2 diabetic patients: intensive blood pressure lowering based on combined perindopril/indapamide with intensive glucose lowering based on gliclazide MR.     

Cinnamaldehyde protects from the hypertension associated with diabetes

Here we investigated cinnamaldehyde (CA) effect on diabetes-induced hypertension. Insulin deficiency was induced by streptozotocin while, insulin resistance by fructose. Rats were left 8 weeks or 12 weeks after STZ or fructose administration respectively. CA (20 mg kg⁻¹ day⁻¹) was daily administered in the last 6 weeks. Then, blood pressure (BP) was recorded. Isolated Aorta reactivity to phenylephrine (PE), KCl, acetylcholine (ACh) was studied as well as nitric oxide (NO) generation plus Ca²⁺ influx. Insulin deficiency was associated with elevated BP, increased response to PE and KCl, decreased response to ACh and impaired NO generation. CA treatment prevented hyperglycemia and its associated impaired vascular reactivity. Insulin resistance was associated with elevated BP while, CA prevented this elevation. Insulin resistance increased response to PE and KCl, decreased response to ACh, while CA treatment normalized response to KCl and PE but not to ACh. Insulin resistance was accompanied with reduced NO generation but exaggerated Ca²⁺ influx while CA restored normal Ca²⁺ influx but did not affect NO generation. In conclusion, CA prevents development of hypertension in insulin deficiency and insulin resistance through normalization of vascular contractility in addition to its insulinotropic effect in insulin deficiency.