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Background: Diabetes is a group of common metabolic disorders that share the characteristic features of hyperglycemia. Ardisia colorata Roxb. leaf extract (AEAC) is reported to be used for the treatment of diabetes. So, the present study is undertaken to evaluate the effect of Ardisia colorata Roxb. leaves on blood sugar by using different hyperglycemic models in Albino rats. Methods: In both the glucose induced hyperglycemia model and streptozotocin induced hyperglycemia model, animals were divided into 4 groups of 6 animals each. 2% gum acacia were taken as control (group 1) and glimepiride 0.2 mg/kg were taken as standard (group 2). Hyperglycemic activity was checked at two different doses i.e., 200 mg/kg (test 1) and 400 mg/kg (test 2) of AEAC (given at group 3 and group 4 respectively) by assessing the decreased in blood sugar level using glucometer by following methods of these two models. The results were analyzed using one-way analysis of variance (ANOVA) followed by Bonferroni test. P value <0.05 was considered significant. Results: Test 2 showed significant reduction in blood sugar level when compared to control after 1 hour and 2 hours of drug administration in both the models whereas test 1 showed significant reduction only in glucose induced hyperglycemia model. There was significant difference when test 2 was compared to test 1 after 1 hour and 2 hours in both the models. Conclusions: The present studies showed that AEAC leaves produced significant reduction in blood sugar level. It might be suggested that flavonoids, alkaloids, tannins and terpenoids were responsible for the hypoglycemic activity of AEAC leaves.
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This study aimed to create and assess a novel self-microemulsifying drug delivery system (SMEDDS) for treating diabetes mellitus that contains glimepiride and Boswellia serrata extract. In the creation of SMEDDS formulations, Transcutol-P was employed as the base oil, while the surfactants Tween 80 and propylene glycol/polyethylene glycol 400 served as the co-surfactants. To improve the formulation, pseudoternary phase diagrams were created. While the SMEDDS of B. serrata extract showed a mean droplet size of 27.63 nm, 98.3% transmittance, a zeta potential of -0.11 mV, and a polydispersity index of 0.287, the glimepiride-optimized SMEDDS showed a mean droplet size of 14.8 nm, 98.5% transmittance, a zeta potential of -0.10 mV. In-vivo evaluation on diabetes-induced rats demonstrated significant reductions in SGOT and SGPT levels with the glimepiride and B. serrata extract SMEDDS compared to diabetic control rats and the marketed glimepiride formulation. The formulation showed promising results in controlling serum total protein, triglyceride, and cholesterol levels. The glimepiride and B. serrata extract SMEDDS also exhibited antioxidant activity, reducing malondialdehyde (MDA) absorbance. Histopathological assessment of kidney and pancreas tissues revealed the protective effects of the concomitant administration of glimepiride and B. serrata extract SMEDDS formulation against diabetes-induced damage. Overall, the developed SMEDDS formulation kit showed superior in-vitro and in-vivo performance, suggesting its potential as an effective therapeutic option for managing diabetes mellitus.
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Objective: This study aimed to enhance the solubility and dissolution of Glimepiride, a new-generation hypoglycaemic agent with low water solubility, by preparing Fast dissolving buccal films (FDBFs) containing Glimepiride solid dispersion.Methods: Glimepiride solid dispersions were fabricated using Polyethylene Glycol 4000 as the carrier by Physical mixture, Solvent evaporation, Kneading, and Fusion method. The optimised solid dispersion was selected based on the drug content and in vitro dissolution data. The final films incorporated with solid dispersion were prepared by the solvent casting technique, wherein the film formulation was optimised using the design of experiment (DoE) approach by applying the Central Composite statistical design. The optimised film formulation was then evaluated for various parameters, including weight variation, folding endurance, disintegration time, thickness, surface pH, and dissolution studies.Results: Among the different methods employed, the kneading method using PEG 4000 in a drug-to-polymer ratio of 1:3 exhibited the highest drug content and in vitro drug release, making it the most promising option. The film formulation that was optimised displayed an accelerated in vitro drug dissolution within a time frame of 10 min, with an average disintegration time of 31.33±0.471.Conclusion: The developed FDBFs loaded with Glimepiride solid dispersion demonstrated a markedly improved dissolution profile, avoidance of extensive first-pass metabolism, and improved patient compliance. The results suggest that the developed FDBFs could be a potential alternative to conventional dosage forms of Glimepiride.
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Introduction@# Sulfonylureas (SUs) are commonly used drugs for type 2 diabetes mellitus (T2DM) in the Philippines. This study aimed to associate genetic variants with poor response to gliclazide and glimepiride among Filipinos.@*Methodology@#Two independent, dichotomous longitudinal substudies enrolled 139 and 113 participants in the gliclazide and glimepiride substudies, respectively. DNA from blood samples underwent customized genotyping for candidate genes using microarray. Allelic and genotypic features and clinical associations were determined using exact statistical methods.@*Results@#Three months after sulfonylurea monotherapy, 18 (13%) were found to be poorly responsive to gliclazide, while 7 (6%) had poor response to glimepiride. Seven genetic variants were nominally associated (p<0.05) with poor gliclazide response, while three variants were nominally associated with poor glimepiride response. For gliclazide response, carboxypeptidase-associated variants (rs319952 and rs393994 of AGBL4 and rs2229437 of PRCP) had the highest genotypic association; other variants include rs9806699, rs7119, rs6465084 and rs1234315. For glimepiride response, 2 variants were nominally associated: CLCN6-NPPA-MTHFR gene cluster – rs5063 and rs17367504 – and rs2299267 from the PON2 loci.@*Conclusion@#Genetic variants were found to have a nominal association with sulfonylurea response among Filipinos. These findings can guide for future study directions on pharmacotherapeutic applications for sulfonylurea treatment in this population.
Тема - темы
GliclazideРеферат
Objective:To analyze the efficacy and safety of dapagliflozin combined with metformin in the treatment of type 2 diabetes.Methods:A prospective research method was adopted. A total of 60 patients with type 2 diabetes who were treated in Huainan Chaoyang Hospital from January 2019 to December 2021 were collected as research objects, and the above patients were divided into the observation group (30 cases) and the control group (30 cases) according to the random number table method. After admission, they were treated with oral metformin sustained-release tablets combined with exercise and diet control. On this basis, the observation group was treated with dapagliflozin, while the control group was treated with glimepiride. The blood glucose-related indexes after 3 months of treatment, blood lipid indexes after 1 month of treatment, and adverse reactions were compared between the two groups of patients.Results:After 3 months of treatment, the fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA 1c) of the two groups were significantly lower than those before treatment, observation group: (6.60 ± 1.01) mmol/L vs. (7.76 ± 1.82) mmol/L, (10.43 ± 2.74) mmol/L vs. (14.05 ± 3.84) mmol/L, (5.90 ± 1.56)% vs. (8.46 ± 2.07)%; control group: (6.77 ± 0.95) mmol/L vs. (7.82 ± 1.38) mmol/L, (10.17 ± 2.23) mmol/L vs. (14.01 ± 2.63) mmol/L, (6.14 ± 1.51)% vs. (8.73 ± 1.58)% ( P<0.05), but there was no difference in FBG, 2 h PBG and HbA 1c between the two groups ( P>0.05). The total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the observation group were significantly lower than those in the control group: (5.02 ± 0.98) mmol/L vs. (5.71 ± 0.77) mmol/L, (2.81 ± 0.69) mmol/L vs. (3.39 ± 0.87) mmol/L ( P<0.05). There was no difference in adverse reactions ( P>0.05). Conclusions:For patients with type 2 diabetes mellitus, on the basis of metformin sustained-release therapy, whether combined with dapagliflozin or glimepiride therapy has good hypoglycemic effect, but dapagliflozin has more advantages in improving blood lipids.
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Department of medicine, Educare institute of dental science Malappuram, Kerala and SafeCare clinics, Tirur, Keralasulfonylureas (SUs) are one of the oldest, time tested and most commonly used oral antidiabetic agent in Type 2 diabetes. Modern SUs like glimepiride and gliclazide XR were preferred over conventional SUs due to its better efficacy and minimal side effects. The use of Modern SUs in the treatment armamentarium of T2DM has evolved, over past few decades. Modern SUs possesses beneficial pancreatic glucose lowering effect and more interestingly extra-pancreatic pleiotropic benefits. This review article discusses on the utility and benefits of SUs beyond glycemic control and explaining on their pleiotropic effects.
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Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.
Тема - темы
Animals , Male , Female , Mice , Quality Control , Tablets/classification , Drug Interactions , Metoprolol/analysis , In Vitro Techniques/methods , Pharmaceutical Preparations/analysis , Total Quality Management/statistics & numerical dataРеферат
【Objective】 To investigate the efficacy and safety of sitagliptin combined with metformin versus glimepiride combined with metformin in newly diagnosed type 2 diabetes patients with severe hyperglycaemia. 【Methods】 A randomized controlled and non-inferiority trial was carried out. A total of 129 newly diagnosed type 2 diabetes patients with severe hyperglycaemia [FPG≥200 mg/mL (11.1 mmol/L) and HbA1c≥9.0%] were enrolled and numerally randomly assigned to two groups. The patients received sitagliptin combined with metformin (n=66) or glimepiride combined with metformin (n=63) for 4 weeks and then metformin alone for another 8 weeks. Glycaemic control, weight changes and β-cell insulin secretory capacity were investigated to demonstrate the efficacy and safety of these two treatments. 【Results】 Mean HbA1c reduction was 4.03% in sitagliptin group and 4.13% in glimepiride group after 3 months of treatment. The lower boundary of the two-sided 95% confidence intervals of the mean HbA1c reduction difference between the two groups was -0.648%, which was more than -0.65%, suggesting that the predefined statistical criterion for non-inferiority was achieved. FPG decreased significantly after one month of intervention in both groups (P0.05). 【Conclusion】 Our study provided evidence that sitagliptin combined with metformin in newly diagnosed diabetes patients with severe hyperglycaemia showed better outcomes in glycaemic remission compared with glimepiride for those who refused insulin injection.
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Background: Antihypertensive agents like Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin-Converting Enzyme Blockers (ARBs) are commonly indicated for patients with both hypertension and diabetes. However, the effect of these agents on blood sugar level or glycated hemoglobin (HbA1c) is still controversial. This study aims at investigating theshort, and long term effects of ACEIs and ARBs on blood sugar level and HbA1c of a group of streptozocin (STZ)-induced NIDDM rats when given in combination with Glimepiride (antidiabetic drug from Sulfonylureas group).Methods: Diabetes mellitus (DM) was induced in 100 Wistar albino adult male and female laboratory rats above 8 weeks old, and weigh between 250-300 gm by the administration of Streptozocin 75% α-anomer. Two weeks later, the100 rats were then randomized into four groups (25 rats each). Groupone was the untreated control group (received placebo only), while other groups (II, III, and IV) were treated by Glimepiride only, Glimepiride plus ARB (Candesartan), and Glimepiride plus ACEI (Enalapril)respectively. HbA1C levels were measured at baseline (pre-test/directly after randomization) to ensure that there was no significant difference between study groups at the baseline, post-test (after two weeks), and delayed-post-test (12 weeks after randomization/ 10 weeks after post-test) to measure short and long-term changes in the study groups.Results: There was no significant difference (p-values >0.05) between the four groups (groups I, II, III, and IV) in the HbA1C mean level at the beginning of this study (two-weeks after randomization and injection of STZ) (mean = 7.62 ±SD = 0.41, 7.72 ±SD = 0.48, 7.66 ±SD = 0.47, and 7.52 ±SD = 0.51respectively). However, two weeks later, treated groups (groups II, III, and IV) showed moderate reduction of HbA1C mean level compared to the untreated (placebo) group I, that was significant in groups III, and IV, and insignificant in group II (mean =7.43±SD 0.54, 6.97±SD 0.33, 6.72±SD 0.26, and 7.71 ±SD 0.44 respectively). Furthermore, treated groups (groups II, III, and IV) showed significant dramatic reduction of HbA1C mean level when compared to the untreated group (group I) (mean = 6.22 ±SD 0.51, 5.24 ±SD 0.62, 5.22 ±SD 0.13, and 7.62 ±SD 0.42 respectively).Overall, treated groups showed significantly lower HbA1C level than placebo groups. Moreover, Glimepiride + Enalapril combination showed a stronger hypoglycemic effect than the Glimepiride + Candesartan combination at post, and post-delayed tests, however, these differences were not significant.Conclusion: The addition of either ACEIs like Enalapril, or ARBs like Candesartan to Sulfonylureas like Glimepiride to in NIDDM patients will synergize its anti-diabetic effect in NIDDM subjects, and might increase the possibility of hypoglycemia. Caution and/or dose adjustment should be considered upon using these agentstogether in patients with hypertension along with diabetes
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Background: Diabetes is a most prevalent chronic disease and has reached to alarming stage in almost all developed and developing countries. Worldwide approximately four hundred millions of people are living with diabetes and it is a leading cause of death. Aims and objectives is to study effectiveness of addition of drug Teneligliptin to Metformin, Glimepiride, Pioglitazone combination in type II Diabetic patients.Methods: This was a cross sectional study carried out in the department of Medicine of a tertiary health care centre during the one year period i.e. January 2017 to January 2018 in the type II diabetic patients. Out of all type II diabetic patients 40 patients who were on the treatment for hypoglycemia with drugs Metformin, Glimepiride, Pioglitazone were selected out of these randomly 20 patients were continued on the previous treatment (Group B) and remaining 20 were given additional drug Teneligliptin (Group A). The statistical analysis was done by unpaired t-test and chi-square test analyzed by SPSS 19 version of software.Results: In this study Authors have seen that the average age in both the groups was comparable i.e. 36.78±6.74 and 38.92±5.87 (p>0.05, t=1.24, df=38), the sex ration was also similar in both the group (p>0.43, χ2=0.43, df=1) and the HbA1C was comparable at 1st Wk. 10±4.56 - 9.87±3.42 (p>0.05, t=1.023, df=38) and 4th Wk. 8±5.23 - 9.67±4.52 (p>0.05, t=1.0804, df=38) but significantly differed at 8th Wk. 7.12±2.34 - 9.92±3.56 (p<0.01, t=3.82, df=38), 12th Wk. 5.98±1.98 - 9.24±2.79 (p<0.001, t=4.26, df=38) respectively in Group A and B.Conclusions: It can be concluded from this study that the addition of Teneligliptin significantly reduced the HbA1c level at the end of 4th wk. and hence superior to conventional Metformin, Glimepiride, Pioglitazone only combination treatment.
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Background: The prevalence of coronary artery disease has been increased in diabetic dyslipidemia; hence the present study would like to compare the dyslipidemic effects of Sitagliptin, Voglibose, and Glimepiride in combination with Metformin in type 2 diabetes mellitus patients.Methods: This study was a Prospective, Randomized Clinical trial conducted at SRM medical College Hospital and Research centre. Potheri, Kancheepuram District in diabetic outpatient department after obtaining approval from Institutional Ethics Committee. The patients receiving antidiabetic drugs were divided into three groups. Patients received Metformin with Sitagliptin were grouped as I, Metformin with Voglibose were named as Group II and Metformin with Glimepiride were marked as Group III. Based on the inclusion and exclusion criteria, in each group, 40 patients were assigned as per simple randomization method. The level of lipid profile and BMI was evaluated at the end of 6 months.Results: There was a significant reduction of Total Cholesterol (TC) in Group II and Group III (p value- <0.001, <0.006). Group I showed significant elevation of HDL-C level with the p value of <0.03. Group III showed significant reduction of Triglyceride (TG) level with the p value of <0.04, significant reduction of Low Density Lipoprotein Cholesterol (LDL-C) level with the p value of <0.02 and significant reduction in Very Low Density Lipoprotein Cholesterol (VLDL-C) level with the p value of <0.05. There was no significant reduction in Body Mass Index (BMI) among the groups. On multiple comparisons, Group III showed higher efficacy in reducing TC, TG, LDL-C and VLDL-C levels.Conclusions: The results of this study were analysed and it could be concluded as Metformin with Glimepiride combination (Group III) showed significant reduction of TC, TG, LDL-C and VLDL-C levels.
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Background: To evaluate the comparison of clinical outcomes of sitagliptin +metformin and glimepiride in uncomplicated Type-2 diabetics.Methods: This one year (July 2016 to August 2017) prospective, open label, observational clinical cohort study was carried out on type-2 diabetics. In this study 299 Type-2 diabetics patients were enrolled and were randomly allocated to two groups viz Group A and Group B. Group A received sitaglitin+metformin (50+500) mg/day and Group B received glimepiride 1mg/day respectively. The follow up started after 10 days of stabilization of the patient and data recorded on 10th day was considered Zero month data and follow up continued up to Six month in each group. Comparison of FPG, PPG and HbA1c was evaluated between zero and six months within group and at six month between groups. Adverse events were recorded and summarized by treatment group.Results: At the end of six months follow up the patients of Group A who received sitaglitin+metformin (50+500) mg/day had greater reduction in FPG, PPG and HbA1c (all P<0.001) was recorded when compared between zero and six month within group. A significant reduction in FPG, PPG and HbA1c (all P<0.01) also recorded in Group B who received glimepiride 1mg/day when compared between zero and six months within group. A statically significant difference (all P<0.05) was recorded at six months between group. The adverse events like hypoglycemic episodes, gastrointestinal adverse events etc were greater in Group B than Group A. Changes in weight also noted in both Groups. Weight loss in Group A and weight gain in Group B was recorded.Conclusions: The present study suggests that a significant difference may be existing in the clinical outcome interm of glycemia control and adverse events between sitagliptin+metformin combination and glimepiride in type-2 diabetic patients.
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OBJECTIVE: To study and compare the dissolution behaviors of glimepiride tablets from two manufacturers, and investigate the correlation between dissolution and absorption. METHODS: The solubility and permeability of glimepiride in different pH media were determined, and the biopharmaceutical characteristics of glimepiride tablets were studied and analyzed. The dissolution curves of glimepiride tablets in different media were plotted by the second dissolution method. The dissolution behaviors of glimepiride tablets from two manufacturers were studied and compared. Based on the data of dissolution curves in vitro, the correlation between dissolution and absorption of glimepiride tablets was studied by computer simulation. The virtual bioequivalence study of the two preparations was evaluated in silico. RESULTS: The solubility of glimepiride increased with the increase of pH value; the permeability decreased with the increase of pH value; the dissolution of glimepiride tablets was less than 10% in the media of pH 1.2 and pH 5.0; the dissolution of principal components in the media of pH 6.0-7.4, FaSSIF and FeSSIF ranged from 20% to 90%; the dissolution and absorption of glimepiride tablets in FaSSIF showed high correlation. CONCLUSION: Glimepiride is classified as a BCS Ⅱ class drug (low solubility and high permeability drugs).The dissolution amount and rate of glimepiride tablets increase with the increase of pH value of the medium. The dissolution curves of glimepiride tablets in media of pH 1.2, pH 6.0, pH 6.8 and pH 7.4 could be used as the characteristic dissolution curves of the preparation. The reference preparation A and generic preparation B of glimepiride tablets are similar in dissolution behavior and shows bioequivalence in the virtual bioequivalence study (n=24). This study can provide reference for drug formulation screening, biopharmaceuticals classification determination and bioequivalence risk assessment.
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Background: The trial was done to evaluate the efficacy and tolerability of hydroxychloroquine when added to stable insulin therapy in combination with metformin and glimepiride in patients with type 2 diabetes (T2DM) compare to sitagliptin.Methods: After two weeks run in period, eligible patients inadequately controlled on long acting, intermediate acting or premixed insulin (HbA1c ?7.5% and ?10%), in combination with metformin and glimepiride were randomised 1:1 to the addition of once daily hydroxychloroquine 400mg or sitagliptin 100mg over 24weeks study period. The primary endpoint was HbA1c change from baseline at week 24. Home based glucometer was used to determine finger stick glucose value to detect hypo or hyperglycemia periodically.Results: At 24 weeks, the addition of hydroxychloroquine significantly (p <0.001) reduced HbA1c by 1.3% compared with Sitagliptin which was 0.9%. A greater proportion of patients achieved an HbA1c level <7% while randomised to Hydroxychloroquine as compared with sitagliptin (31 vs. 18% respectively; p <0.001). The addition of hydroxychloroquine significantly (p<0.001) reduced fasting plasma glucose by 31.0mg/dl (vs 23.2mg/dl with sitagliptin) and post prandial plasma glucose by 52.1mg/dl (vs 41mg/dl with sitagliptin) relative to sitagliptin. The difference in mean value of total daily insulin dose showed a highly significant decrease (P <0.0001) from baseline to end of the treatment with hydroxychloroquine i.e. from 41±10.2 to 31.87±16.49 IU as compare to sitagliptin i.e. from 41±10.6 to 37.91±11.71 IU. And also highly significant (P <0.0001) decrease in mean weight was observed at the end of trial with hydroxychloroquine.Conclusions: Hydroxychloroquine decreases HbA1c in patients whose type 2 diabetes is poorly controlled with stable-dose insulin therapy with metformin and glimepiride.
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Introduction@#Diabetes in the Philippines is a major and growing health issue. From its prevalence of 2.8 million in 2000, it was projected by the World Health Organization to reach 7.8 million by 2030. Glimepiride has been found to be effective and well-tolerated, as monotherapy and in combination with metformin, in managing glycemic levels among type II diabetes mellitus (T2DM) patients. This study aimed to assess the safety and efficacy of a sustained release (SR) fixed-dose combination (FDC) preparation of glimepiride and metformin in the treatment of Filipino patients with T2DM.@*Methods@#This open-label, observational, multicenter, post-marketing study, conducted from April 2012 to December 2013, included 20 to 75-year-old patients with T2DM, presenting with 7% to 11% HbA1c or 110-250 mg/dL fasting blood sugar, insulin-naive, and in consideration for management with a glimepiride-metformin FDC. Baseline data were collected. Patients were prescribed with glimepiride-metformin FDC SR 2/500 mg/tab for a six-month treatment period. Follow-up data were collected on the third and the sixth month of treatment. Patients who missed one follow-up were included in population for safety analysis. Patients who completed both follow-up schedules make up the per-protocol population for efficacy analysis. Adverse events (AEs) were reported in frequencies and percentages. Repeated measures analysis of variance (ANOVA) was used for efficacy analysis on HbA1c and FBG data.@*Results@#From 1,052 enrollees, 795 patients had sufficiently filled data forms and attended at least one follow-up schedule; this is the population whose data was analyzed for this study. Fifty-nine AEs were reported; only 21 incidents of hypoglycemia were assessed to be definitely, probably, or possibly related to the study drug. Repeated measure ANOVA showed that the mean ± SD HbA1c at month three (7.15 ± 1.22%) and month six (6.80 ± 1.17%) were significantly lower than baseline (8.67 ± 1.10%). The mean ± SD FBG at month three (133.20 ± 35.46 mg/dL) and month six (122.47 ± 29.34 mg/dL) were also significantly lower than baseline (176.85 ± 41.24 mg/dL). The differences in HbA1c and FBG changes between those with concomitant OAD and those without were non-significant.@*Conclusion@#Fixed-dose combination of glimepiridemetformin is a drug with a tolerable profile and favorable benefits in treating patients with T2DM.
Тема - темы
MetforminРеферат
OBJECTIVE: To investigate the effects of glimepiride combined with metformin on glucose and lipid metabolism, islet function and serum miR-126 expression of newly diagnosed type 2 diabetes patients. METHODS: A total of 100 patients with newly diagnosed type 2 diabetes in Nanchuan Hongren Hospital of Chongqing during Jan. 2014-Jan. 2017 were divided into observation group and control group according to random numble table, with 50 cases in each group. Control group was given Metformin hydrochloride sustained-release tablets (Ⅱ) with initial dose of 0. 5 g, once a day, adjusted to 0. 5 g 12 weeks later, twice a day, maximal dose of 1 g at meal or after meal. Observation group was additionally given Glimepiride tablets 2 mg, once a day, at breakfast, on the basis of control group. Both group were treated at lasted for 24 weeks. The levels of blood glucose (FPG, 2 hPG, HbA1c), blood lipid (TC, TG), islet function (FINS, 2 hINS, FCP, 2 hCP, HOMA-IR), serum miR-126 before and after treatment and the occurrence of ADR were observed in 2 groups. RESULTS: Before treatment, there was no statistical significance in the levels of blood glucose, blood lipid, islet function or serum miR-126 expression between 2 groups (P＞0. 05). After treatment, the levels of blood glucose, blood lipid and HOMA-IR in 2 groups were significantly lower than before treatment, and the levels of blood glucose and HOMA-IR in observation group were significantly lower than control group. The levels of FINS, 2 hINS, FCP and 2 hCP, serum miR-126 expression in 2 groups were significantly higher than before treatment, and the observation group was significantly higher than control group, with statistical significance(P＜0. 05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS: Glimepiride combined with metformin can significantly improve glucose and lipid metabolism, islet function, and regulate serum miR-126 expression without increasing the occurrence of ADR.
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Objective:To assess the influence of glimepiride on the plasma concentrations and antihypertensive effects of losartan and its active metabolite losartan carboxylic acid(E-3174) in the patients with type 2 diabetes mellitus and hypertension. Methods:Pragmatic randomized controlled trial was used in the clinical study. Forty-five patients were enrolled and randomized into glimepiride group and the control group. Losartan was used as the antihypertensive drug in the two groups. After two-week interference,the plasma concentrations of losartan and its active metabolite E-3174 were determined using an LC-MS/MS method and the reduction of hyperten-sion was measured. Results:The plasma trough concentrations of losartan in glimepiride group was not higher than those in the control group,and those of E-3174 in glimepiride group was not lower than those in the control group. Additionally,the reduction of hyperten-sion was similar in the two groups. Conclusion: Glimepiride does not influence the plasma concentrations and the antihypertensive effects of losartan and its active metabolite E-3174 in the patients with type 2 diabetes mellitus and hypertension, suggesting no drug-drug interactions between them. Owing to the small sample,large clinical trial should be performed to confirm the above conclusion.
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Objective To compare the efficacy and safety of compound pioglitazone hydrochloririe glimepiride tablet and glimepiride tablet in the treatment of type 2 diabetic mellitus(T2DM) for evaluating the effectiveness and safety of compound pioglitazone hydrochloride glimepiride tablet for treating T2DM.Methods The random,double-blind,double-dummy,positive drugs parallel control clinical study method was adopted.Thirty-three T2DM patients with poorly controlled blood glucose were randomly assigned to the test group(n=22) and control group(n=11) by the 2 ∶ 1 ratio.The test group was given compound pioglitazone hydrochloride glimepiride tablet,while the control group received glimepiride tablet.The treatment cycle was 12 weeks.The differences of FBG,HbA1c,FINS and HOMA-IR in the two groups were compared between before and after treatment.Moreover the changes of body mass,blood pressure and blood lipids as well as adverse events occurrence were compared between the two groups.Results Thirty-one cases finished the treatment follow up(21 cases in the test group and 10 cases in the control group);the decreased amplitudes of HbA1c levels after 12-week treatment in the test group and control group were (0.99 ± 1.87)％ and (-0.02 ± 0.90) ％ respectively,which of FPG were (0.94 ± 1.87) mmol/L and (0.37 ± 2.62) mmol/L respectively.The FPG and HbA1c levels after treatment in the test group were decreased compared with before treatment,the difference was statistically significant (P＜0.01).The change difference of FPG and HbA1c in the control group had no statistical difference(P＞0.05).FINS and HOMO-IR in the test group were significantly decreased before and after treatment,the difference was statistically significant (P＜0.01).The incidence rate of hypoglycemia had no statistically significant difference between the test group and control group.Conclusion The effectiveness of compound pioglitazone hydrochloride glimepiride tablet in treating T2 DM is superior to the single use of glimepiride,while the safety is equivalent to single use of glimepiride.
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Glimepiride, a third generation sulfonylurea, is an antihyperglycemic agent widely used to treat type 2 diabetes mellitus. In this study, an untargeted urinary metabolomic analysis was performed to identify endogenous metabolites affected by glimepiride administration. Urine samples of twelve healthy male volunteers were collected before and after administration of 2 mg glimepiride. These samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and then subjected to multivariate data analysis including principal component analysis and orthogonal partial least squares discriminant analysis. Through this metabolomic profiling, we identified several endogenous metabolites such as adenosine 3′, 5′-cyclic monophosphate (cAMP), quercetin, tyramine, and urocanic acid, which exhibit significant metabolomic changes between pre- and posturine samples. Among these, cAMP, which is known to be related to insulin secretion, was the most significantly altered metabolite following glimepiride administration. In addition, the pathway analysis showed that purine, tyrosine, and histidine metabolism was affected by pharmacological responses to glimepiride. Together, the results suggest that the pharmacometabolomic approach, based on LC-MS/MS, is useful in understanding the alterations in biochemical pathways associated with glimepiride action.
Тема - темы
Humans , Male , Adenosine , Diabetes Mellitus, Type 2 , Histidine , Insulin , Least-Squares Analysis , Mass Spectrometry , Metabolism , Metabolomics , Principal Component Analysis , Quercetin , Statistics as Topic , Tyramine , Tyrosine , Urocanic Acid , VolunteersРеферат
Objective To compare the clinical effects and safety of rosiglitazon and glimepiride separately combined with insulin in the treatment of patients with T2DM for first diagnosed.Methods 150 patients with T2DM for first diagnosed were chosen and randomly divided into two groups according to digital table,including rosiglitazon group (60 patients) with rosiglitazon,and glimepiride group (60 patients) with glimepiride on the basis of glargine insulin.The compliance time of blood glucose,the insulin used doses,the levels of BMI,FBG,2hFBG,HbA1 c,FC-P,2hC-P,HOMA-IR and HOMA-islet before and after treatment and hypoglycemia incidence of both two groups were compared.Results There were no statistically significant differences in the compliance time of blood glucose and the insulin used doses between 2 groups (P ＞ 0.05).The levels of BMI before and after treatment of the glimepiride group were (25.03 ± 3.25) kg/m2,(27.42 ± 3.49) kg/m2,respectively,which of the rosiglitazon group were (24.71 ± 3.18) kg/m2,(24.80 ± 3.30) kg/m2,respectively.The BMI after treatment of the glimepiride group was significantly lower than that of the rosiglitazon group (t =3.37,P ＜ 0.05).There were no statistically significant differences in the levels of FBG,2hFBG,HbAlc,FC-P,2hC-P,HOMA-IR and HOMA-islet between the two groups(all P ＞ 0.05).The incidence rates of hypoglycemia in the rosiglitazon group and glimepiride group were 14.67％,2.67％,respectively.The incidence rate of hypoglycemia of the glimepiride group was significantly lower than that of the rosiglitazon group (x2 =7.15,P ＜ 0.05).Conclusion Rosiglitazon and glimepiride separately combined with insulin in the treatment of patients with T2DM for first diagnosed possess the same clinical effects in controlling the blood glucose levels and improving the islet function;and glimepiride application can efficiently prevent the weight gain amount and hypoglycemia.