Combination Of Glimepiride Research Articles

Comparison of the efficacy and safety of Glimepiride and Glipizide as add-on therapy with metformin in patients of type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder carrying an enormous burden of morbidity and mortality because of its characteristic complications, many of which are preventable with strict glycaemic control. Initial management of T2DM consists of non-pharmacological interventions; it those fail, an oral anti-diabetic drug, most typically metformin, is started. Combination therapy is initiated only when monotherapy fails to achieve glycaemic control. Glipizide and glimepiride, a second and a third generation sulphonylurea respectively, are the commonest drugs added to metformin when the latter fails to achieve euglycaemia on its own. Aims and Objectives of the study were to compare the efficacy and safety of glimepiride and glipizide as add-on therapy to metformin in patients of uncontrolled T2DM.Methods: This prospective, observational and analytical study was conducted by the Department of Pharmacology among patients attending the Internal Medicine OPD of a tertiary-care hospital. Fifty patients were assigned to two groups of 25 patients each: Group A - Glimepiride + Metformin and Group B - Glipizide + Metformin. Patients were followed up for three months. Data were analysed by Student's t-test.Results: There was a significant decrease in the HbA1c, FBS and 2h-PPBS in both groups. However there was no significant difference between the two groups during the three-month period of follow-up.Conclusions: The combination of glimepiride and metformin is just as effective and safe as the combination of glipizide and metformin in patients not controlled on monotherapy with metformin.

Pharmacokinetic interactions between glimepiride and rosuvastatin in healthy Korean subjects: does the SLCO1B1 or CYP2C9 genetic polymorphism affect these drug interactions?

To improve cardiovascular outcomes, dyslipidemia in patients with diabetes needs to be treated. Thus, these patients are likely to take glimepiride and rosuvastatin concomitantly. Therefore, this study aimed to evaluate the pharmacokinetic (PK) interactions between these two drugs in healthy males and to explore the effect of SLCO1B1 and CYP2C9 polymorphisms on their interactions in two randomized, open-label crossover studies. Glimepiride was studied in part 1 and rosuvastatin in part 2. Twenty-four participants were randomly assigned to each part. All subjects (n=24) completed part 1, and 22 subjects completed part 2. A total of 38 subjects among the participants of the PK interaction studies were enrolled in the genotype study to analyze their SLCO1B1 and CYP2C9 polymorphisms retrospectively (n=22 in part 1, n=16 in part 2). Comparison of the PK and safety of each drug alone with those of the drugs in combination showed that both glimepiride and rosuvastatin did not interact with each other and had tolerable safety profiles in all subjects. However, with regard to glimepiride PK, the SLCO1B1 521TC group had a significantly higher maximum plasma concentration (Cmax,ss) and area under the plasma concentration–time curve during the dose interval at steady state (AUCτ,ss) for glimepiride in combination with rosuvastatin than those for glimepiride alone. However, other significant effects of the SLCO1B1 or CYP2C9 polymorphism on the interaction between the two drugs were not observed. In conclusion, there were no significant PK interactions between the two drugs; however, the exposure to glimepiride could be affected by rosuvastatin in the presence of the SLCO1B1 polymorphism.

The complete review on analytical and formulation technique of glimepiride

Glimepiride is a third generation sulfonylurea derivative which is commonly used in the treatment of non-insulin dependent Type 2 diabetes mellitus. The clinical and pharmaceutical analysis of the drug requires effective analytical procedures for quality control and pharmacodynamic and pharmacokinetic studies as well as stability study. In the present review, we have compiled the published analytical methods reported for the determination of glimepiride in pharmaceutical formulations and biological samples. Most extensively used Techniques like spectrophotometry and high-performance chromatography (HPLC) methods were reported in the table 1- 4. In table 1 and table 2 show the summary of the reported spectroscopic methods for glimepiride alone and glimepiride in combination respectively indicating the basic principle, ?max, solvent etc. Whereas HPLC methods for glimepiride alone and glimepiride in combination respectively reported in table 3 and table 4 which indicate summary like stationary phase, mobile phase, flow rate and retention time. One TLC method were reported in table 5 and different type of 24 glimepiride formulations with used polymers have been reported in table 6. Definitely this tabulated information will helpful for all researchers who are currently working on Glimepiride. So this paper should have very helpful for development of new HPLC method, development of new spectrophotometric method as well as development of new formulation method for the glimepiride.

Comparison of efficacy and safety of metformin and vildagliptin versus metformin and glimepiride in patients of Type 2 diabetes mellitus

Background: Diabetes mellitus is a heterogeneous chronic metabolic disorder principally characterized by persistent hyperglycemia resulting from defects in insulin action and/or insulin secretion. In course of time, prolonged hyperglycemia and associated metabolic aberrations result in tissue toxicity manifested as accelerated atherosclerosis, renoretinal microangiopathy, and neuropathy leading to a variety of vascular, neurological, and focal complications. Aim and Objective: The aim of this study is to evaluate the efficacy and safety of metformin and vildagliptin versus metformin and glimepiride in patients with Type 2 diabetes mellitus. Materials and Methods: This is a longitudinal interventional study. A total of 60 patients were enrolled in the study. Those patients who were already on metformin 500 mg bid with poor glycemic control were included in the study. These 60 patients were divided into two groups each consisting of 30 patients. Group A patients received glimepiride 1 mg bid and metformin 500 mg bid. Group B patients received vildagliptin 50 mg bid and metformin 500 mg bid. The total period of the study was 3 months. Results: After 3 months of treatment, both the groups caused a significant decline in blood glucose levels both fasting blood sugar (FBS) as well as postprandial blood sugar (PPBS) levels. There was a significant difference between the two groups in reducing the FBS levels and PPBS. Hemoglobin A1c (HbA1c) was also reduced significantly in both groups at 12 weeks. After 3 months of therapy, there was a reduction in HbA1C in B group. The reduction of HbA1C was not statistically significant between the two groups. Adverse effects were more with metformin and glimepiride group at the end of 3 months therapy. There was a significant difference in the incidence of adverse effects between both the groups. Conclusions: Vildagliptin and metformin combination provided better efficacy comparable to that of glimepiride and metformin combination and resulted in better adverse effect profile with lower risks of hypoglycemia and weight gain.

Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control.

Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control.

Safety and Efficacy of Fixed Dose Combination of Voglibose, Glimepiride and Metformin in Indian Type 2 Diabetes Mellitus Patients

Worldwide diabetes mellitus is highly prevalent and economically devastating illness. This study was a post marketing surveillance (PMS), non-randomized, open, non-comparative, mono-centric study. The drug administered was a fixed dose combination of voglibose 0.2 mg; glimepiride ½ mg and metformin 500 mg sustained release (SR). Fifty type 2 diabetic patients were given fixed dose combination twice daily with major meals for 3 months. Baseline value was recorded for glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and post prandial blood glucose/hyperglycemia (PPHG) level. There was significant decrease from baseline in HBA1c value 10.6 ± 1.3 vs. 6.6 ± 0.4 (P< 0.0001), FPG levels 208.33 mg/dl vs. 118.06 (P< 0.0001), and PPHG levels 360.14 mg/dl vs. 168.36, (P< 0.0001) after 3 months of treatment. The combination was found to be effective in controlling both fasting and post prandial glucose level and was well tolerated. Investigator commented that the use of triple drug combination is a good option in the management of type 2 diabetes which controls both fasting as well as post prandial blood glucose and ultimately HbA1c values.

Open-label randomized non-inferiority trial of a fixed-dose combination of glimepiride and atorvastatin for the treatment of people whose Type 2 diabetes is uncontrolled on metformin.

To evaluate, in a randomized, open-label study, the non-inferiority of a bioequivalent fixed-dose combination of glimepiride and atorvastatin vs. separately co-administered tablets in people with Type 2 diabetes mellitus. Participants with HbA1c ≥53 to <80mmol/mol (≥7.0 to <9.5%), average fasting blood glucose >7.0mmol/l, who were on metformin for ≥3months, were randomized to combination (n=215) or co-administered glimepiride and atorvastatin (n=212) once daily for 20weeks. Up-titration of glimepiride (1-4mg) and atorvastatin (10-20mg) were based on average fasting blood glucose and LDL cholesterol, respectively. Co-primary endpoints were change from baseline to week 20 in HbA1c and LDL cholesterol. Non-inferiority was demonstrated for both co-primary endpoints: the upper limits of 95% CIs for differences (combination-reference) were less than the prespecified margins of 3.3mmol/mol (0.3%) for change from baseline in HbA1c [difference 0.1mmol/mol (95% CI -1.6, 1.9); 0.01% (95% CI -0.15, 0.17)] and 6% for percentage change from baseline in LDL cholesterol [difference 0.87% (95% CI -2.47, 4.21)]. Similar proportions of participants on combination and reference had treatment-emergent adverse events (64 vs. 61%). More participants on combination had hypoglycaemia (21 vs. 13%); most events were considered by the treating physician to be unrelated to study drug. The combination was non-inferior to separately co-administered tablets and the safety profile was consistent with the known profiles of glimepiride and atorvastatin. The observed increase in hypoglycaemia on the combination cannot be explained, but may be attributable to non-systematic collectiof glucose readings and may have been influenced by reporting bias in this open-label trial.

Genotoxicity evaluation of metformin and glimepiride by micronucleus assay in exfoliated urothelial cells of type 2 diabetes mellitus patients

Micronucleus (MN) assay was performed on the exfoliated urothelial cells to detect the genotoxic effects of the anti-hyperglycemic drugs, metformin and glimepiride in T2DM patients and to use it as a biomarker for DNA damage by assessing the frequency of micronuclei in the exfoliated urothelial cells. A total of 201 subjects (147 T2DM patients & 54 Normal cases) were selected from diverse age groups (25–75 years) and the mean MN frequency was examined per 1000 cells in all the subjects. Relative to the control group (5.02 ± 1.01), an increased MN frequency was observed in females (26.15 ± 2.15) when compared to males (23.08 ± 2.09) in T2DM patients. Further analysis showed that there was a profound increase in the number of MN in the patients using metformin alone (23.02 ± 4.44), or combination of metformin & glimepiride (24.98 ± 2.87) than to the subjects using glimepiride alone (17.52 ± 3.28). It has been proven by this simple, reliable and non-invasive method that metformin has a potential role in causing genotoxicity and that the MN observed in exfoliated urothelial cells could be used as a reliable biomarker in monitoring the genotoxic risk of the anti-hyperglycemic drugs.

Validation of RP-HPLC method and stress degradation for the combination of metformin HCl, atorvastatin calcium and glimepiride: application to nanoparticles.

A stability-indicating high-performance liquid chromatography (HPLC) procedure was developed for the determination of metformin HCl (MTH), atorvastatin calcium (AC) and glimepiride (GP) in combination and their main degradation products. The separation and quantization were achieved on a 5-µm Qualisil gold, C18 column (4.6 mm × 250 mm). The mobile phase selected was phosphate buffer (pH 2.9)-organic phase in proportion of 70:30. Organic phase consisted of methanol-acetonitrile (90:10) at a flow rate of 1 mL/min and detection of analytes was carried out at 230 nm. The method exhibited good linearity over the range of 10-60 µg/mL for MTH, 2-20 µg/mL for AC and 5-30 µg/mL for GP. Square of the correlation coefficients was found to be >0.999. Various stress degradation studies were carried out in combination as per International Conference of Harmonization (ICH) guidelines for 4 h. The recovery and precision were determined in terms of intraday and interday precisions and expressed as relative standard deviations. These were <1 and <2%, respectively. Finally, the applicability of the method was evaluated in nanoparticle analysis of MTH, AC and GP as well as in stability studies of nanoformulation.

Evaluation of fixed dose combination of glimepiride and metformin in patients with type 2 diabetes. Results of Russian observational study

Aim. To investigate the efficacy and safety of combined glimepiride and metformin therapy in patients with type 2 diabetes mellitus (T2DM). Materials and methods. A multi-centre, open-label, prospective, observational study was conducted. A total of 1200 patients with T2DM inadequately controlled with metformin, glimepiride or combination of metformin + glimepiride were enrolled. Change in serum glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial blood glucose (PPG) levels; weight; waist circumference and hypoglycemic episodes were evaluated. Results. Baseline HbA1c levels (8.24% ? 0.42%) were significantly reduced after 12 weeks of treatment (7.48% ? 0.48%) and at the end of the study. (6.88% ? 0.56%). Target HbA1c levels (?7%) were achieved in 65.1% of patients at the final visit at 24 weeks. FPG and PPG levels decreased by 1.45 ? 1.14 mmol/l and 2.17 ? 1.27 mmol/l respectively (p &lt; 0.001). No severe hypoglycemic events were reported. Body mass index reduced by 0.85 ? 1.28 kg/m2 (p &lt; 0.001). Conclusion. . Combined glimepiride and metformin therapy significantly improved long-term glycemic control in patients with T2DM during the period of 24 weeks. without additional risk of hypoglycemic events or weight gain.

Interaction study between Ocimum sanctum and Glimepiride (sulfonylurea derivative) in diabetic rats

The present study was intended to discover the interaction between Ocimum sanctum(O. sanctum) and Glimepiride, a sulfonylurea derivative used in the treatment of type-2 diabetes, in diabetic rats to suggest an alteration in the dose of Glimepiride in case of hypoglycaemia. LD50 studies for the aqueous extract of O. sanctum leaf were carried out in albino mice up to the dose level of 2000 mg/kg. O. sanctum at low, medium and high doses(100, 200 and 400 mg/kg, per oral), respectively and Glimepiride ?(half) therapeutic dose, therapeutic dose and 2 time therapeutic dose(0.036, 0.072 and 0.144 mg/200 g, per oral) were selected. After the treatment with O. sanctum and Glimepiride as single doses and in various combinations of these two drugs in streptozotocin-induced diabetic rats serum glucose levels in all the groups were analysed by the glucose oxidase-peroxidase method. When administered alone as single doses both aqueous extract of O. sanctum leaf and Glimepiride produced a significant anti-diabetic effect in diabetic rats. The anti-diabetic effect observed with combination of aqueous extract of O. sanctum leaf and Glimepiride was significant and more when compared to either of the drugs given alone. There was a definite interaction that necessitates dose readjustment of Glimepiride and further glucose levels are to be frequently monitored to avoid complication of hypoglycemic condition with aqueous extract of O. sanctum leaf and Glimepiride combination.

Influence fixed combination of glimepiride and metformine SR on carbohydrate and lipid metabolism dynamics of plasma adipocines level and arterial wall stiffness

Influence fixed combination of glimepiride and metformine SR on carbohydrate and lipid metabolism dynamics of plasma adipocines level and arterial wall stiffness

Comparative evaluation of combination of metformin and glimepiride with that of metformin and sitagliptin in type 2 diabetes mellitus with respect to glycemic targets

Background: Sitagliptin, an oral and selective dipeptidyl peptidase-4 inhibitor, represents a novel therapeutic approach for the treatment of type 2 diabetes mellitus. Metformin and glimepiride are most commonly used oral hypoglycemic agents. Objective: To compare combination of metformin and glimepiride with that of metformin and sitagliptin in patients with type 2 diabetes mellitus. Materials and Methods: The study was conducted by Department of Pharmacology, Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, Uttarakhand, India, in Medicine OPD for 1 year. Total 60 patients with type 2 diabetes mellitus were included in the study. The patients were divided into two groups: Group I (n = 30), patients were put on metformin 500 mg + glimepiride 1 mg once daily and Group II, (n = 30), patients were put on metformin 500 + sitagliptin 50 mg once daily. The patients were stabilized for 2 weeks and followed up every 6 weeks for 24 weeks. Fasting blood sugar (FBS) and postprandial blood sugar (PPBS) were measured at every follow-up; glycosylated hemoglobin (HbA1c) was measured at 0 and 24 weeks. Analysis was done using t-test, and a p-value of 0.05), PPBS (p 0.05) was done. Most common adverse drug reactions were hypoglycemia, abdominal discomfort, weight loss, and nausea/vomiting. Conclusion: Both groups showed significant improvement in FBS, PPBS, and HbA1c at the end of the study period. Intergroup comparison showed significant improvement in PPG in group II (with a combination of metformin and sitagliptin) at the end of the study.

Evaluation of Pharmacokinetic Drug Interactions Between Gemigliptin (Dipeptidylpeptidase-4 Inhibitor) and Glimepiride (Sulfonylurea) in Healthy Volunteers

PurposeGemigliptin is approved for the treatment of type II diabetes mellitus. Sulfonylureas are commonly used in combination with other antidiabetic drugs to improve glycemic control. The objective of this study was to evaluate the pharmacokinetics, safety, and tolerability of gemigliptin and glimepiride combination therapy compared with those of monotherapies.MethodsA randomized, open-label, crossover study was performed on healthy Korean male volunteers. Each subject received the following treatments (A and B) with a 7-day washout period: treatment A consisted of gemigliptin 50 mg once daily administered orally for 6 days, followed by concomitant oral dosing of glimepiride 4 mg and gemigliptin 50 mg on day 7; treatment B consisted of a single dose of glimepiride 4 mg. Blood samples were collected up to 24-h postdose on day 6 (gemigliptin) and day 7 (gemigliptin and glimepiride) following treatment A, and on day 1 (glimepiride) following treatment B. Concentrations of gemigliptin, glimepiride, and metabolites were determined using validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). Safety assessments were performed throughout the study.ResultsTwenty-three subjects completed the study. The geometric mean ratios (GMRs) of C max,ss and AUCτ,ss for gemigliptin were 1.0097 [90 % confidence interval (CI) 0.924–1.103] and 0.9997 (90 % CI 0.976–1.024), respectively. For glimepiride, the GMRs of C max and AUClast were 1.031 (90 % CI 0.908–1.172) and 0.995 (90 % CI 0.902–1.097), respectively. Both combination and monotherapy were well tolerated, and no serious adverse events were reported.ConclusionGemigliptin and glimepiride did not alter the pharmacokinetic properties of each other when they were co-administered in healthy volunteers, and were generally tolerated.

EFFECTS OF METFORMIN PLUS GLICLAZIDE VERSUS METFORMIN PLUS GLIMEPIRIDE ON CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

High plasma glucose level, lipid profile disturbances and high plasma homocysteine (Hcy) are important risk factors for cardiovascular diseases in patients with type 2 diabetes. This study was conducted to evaluate and compare effects of glimepiride/metformin combination versus gliclazide/metformin combination on cardiovascular risk factors in type-2 diabetes mellitus (T2DM) patients. One hundred and eighty T2DM patients were randomly allocated for treatment with placebo (control), metformin (500 mg twice daily), glimepiride (3mg once daily), gliclazide (80 mg once daily), metformin plus glimepiride or metformin plus gliclazide for 3 months. We evaluated plasma levels of glucose (PG), glycated hemoglobin (HbA1C), Hcy, vitamin B12, folic acid and lipid profile before treatment and 3 months post treatment. Compared to metformin treated patients, glimepiride plus metformin induced significant reductions in: fasting plasma glucose, postprandial PG, HbA1C % and plasma Hcy level. Conversely, plasma folic acid and vitamin B12 were significantly increased. The levels of total cholesterol and triglyceride were significantly decreased; low-density lipoprotein was markedly decreased, whereas high-density lipoprotein was significantly increased and hence risk ratio was significantly decreased. Similar results but with lower values were obtained using combination of metformin plus gliclazide on glycemic control only. Combination of glimepiride with metformin was superior to gliclazide plus metformin in alleviating the cardiovascular risk factors in type 2 diabetes mellitus patients.

Therapeutic adherence: A prospective drug utilization study of oral hypoglycemic in patients with type 2 diabetes mellitus

ObjectiveTo determine the drug utilization patterns and outcomes of treatment in terms of metabolic control in the type 2 diabetic patients on oral hypoglycemic agents in the outpatient department in the teaching hospital of Hamdard University, New Delhi, India. MethodsPatients with established type 2 diabetes (n=184) visiting the outpatient department were interviewed using a structured questionnaire over a period of five months. ResultsMajority of the type 2 diabetic patients in this setting were treated with a multiple oral hypoglycemic agents. The most commonly prescribed oral hypoglycemic agent was biguanides (metformin) followed by sulfonylureas (glimepiride), thiazolidinediones (pioglitazone), alpha-glucosidase inhibitors (miglitol) and dipeptidyl peptidase-4 inhibitors (vildagliptin). As monotherapy metformin was the most common choice followed by glimepiride and voglibose, the most prevalent multiple therapy was a three-drug combination of glimepiride + metformin + pioglitazone. The study showed poor compliance to the prescribed therapy. ConclusionsThis study prospected the need of patient education and counselled to enhance the patient compliance for prescribed oral hypoglycemic agents and concomitant drugs. There is need for diet control as well as blood glucose and HbA1c monitoring. Metabolic control was found to be poor in the study population. HbA1c monitoring was underutilized. Clinical monitoring of patient's adherence to the prescribed treatment to achieve good glycemic control is recommended. Measures should be taken to improve patient's adherence to the prescribed treatment.

Efficacy and safety of vildagliptin in patients with type 2 diabetes mellitus inadequately controlled with dual combination of metformin and sulphonylurea

AimThe broadly used combination of metformin and sulphonylurea (SU) often fails to bring patients to glycaemic goal. This study assessed the efficacy and safety of vildagliptin as add-on therapy to metformin plus glimepiride combination in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control.MethodsA multicentre, double-blind, placebo-controlled study randomized patients to receive treatment with vildagliptin 50 mg bid (n = 158) or placebo (n = 160) for 24 weeks.ResultsAfter 24 weeks, the adjusted mean change in haemoglobin A1c (HbA1c) was −1.01% with vildagliptin (baseline 8.75%) and −0.25% with placebo (baseline 8.80%), with a between-treatment difference of −0.76% (p < 0.001). Significantly more patients on vildagliptin achieved the HbA1c target <7% (28.3% vs. 5.6%; p < 0.001). The difference in fasting plasma glucose reduction between vildagliptin and placebo was −1.13 mmol/l (p < 0.001). In subgroup of patients with baseline HbA1c ≤8%, vildagliptin reduced HbA1c by 0.74% from baseline 7.82% (between-treatment difference: –0.97%; p < 0.001) with significantly more patients achieving the HbA1c target <7% (38.6% vs. 13.9%; p = 0.014). Vildagliptin was well tolerated with low incidence of hypoglycaemia, slightly higher than with placebo (5.1% vs. 1.9%) and no clinically relevant weight gain.ConclusionsVildagliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin plus glimepiride combination. The addition of vildagliptin was well tolerated with low risk of hypoglycaemia and weight gain. This makes vildagliptin an attractive treatment option for patients failing on metformin plus SU particularly in patients with baseline HbA1c ≤8%.

Comparison of the efficacy of sitagliptin and glimepiride dose-up in Japanese patients with type 2 diabetes poorly controlled by sitagliptin and glimepiride in combination.

The goal of the study was to examine the effects of sitagliptin dose-up or glimepiride dose-up in Japanese patients with type 2 diabetes who were controlled inadequately by sitagliptin and glimepiride in combination. A multicenter, prospective, randomized, open-label study was carried out in 50 patients with type 2 diabetes treated with sitagliptin and low-dose glimepiride. The patients were randomly assigned to receive the addition of 50mg/day sitagliptin or 0.5mg/day glimepiride. The primary end-point was the percentage change in glycated hemoglobin (HbA1c). During a follow-up period, the difference in the percentage changes in HbA1c between the two groups was not significant (P=0.13). However, HbA1c was significantly decreased by glimepiride dose-up (P<0.01 vs baseline), but not by sitagliptin dose-up (P=0.74). Univariate linear regression analyses showed that the percentage change in HbA1c was significantly associated with the serum level of arachidonic acid (AA) in both groups. There was no significant difference in the HbA1c-lowering effects between the two groups. However, a significant HbA1c-lowering effect from baseline of glimepiride dose-up was found, and the AA level showed a negative correlation with the decrease in HbA1c in the sitagliptin dose-up group, but a positive correlation in the glimepiride dose-up group. These findings suggest that the AA level is associated with HbA1c reduction in response to dose-up with these drugs in patients with type 2 diabetes in a combination therapy with sitagliptin and glimepiride. This trial was registered with UMIN (no. 000009544).

Enhanced Bioavailability of Glimepiride in the Presence of Boswellic Acids in Streptozotocin-Induced Diabetic Rat Model

The effect of Boswellia serrata standardized extract (BSE) and Boswellic acids (BA) on the pharmacokinetics and pharmacodynamics of glimepiride in normal as well as diabetic rats was studied. In normal and streptozotocin induced diabetic rats the combination of glimepiride with BSE and BA increased all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t½, MRT and decreased the clearance, Vd markedly as compared with the control group. In pharmacodynamic studies, the combination of glimepiride with BSE and BA provided significant protection against the diabetes induced alterations in the biochemical parameters. In addition, the combination of glimepiride with BSE and BA also improved the total antioxidant status and reduced the lipid peroxide levels significantly in diabetic rats compared with BSE, BA and glimepiride alone treated groups. The results revealed that a combination of glimepiride with BSE and BA led to the enhancement of the bioavailability of glimepiride by inhibiting the CYP2C9 enzyme, which suggested that boswellia might be beneficial as an adjuvant to glimepiride in a proper dose, in diabetic patients

Evaluation of Efficacy and Tolerability of Glimepiride and Metformin Combination

The objectives of this study were to evaluate the efficacy and tolerability of glimepiride plus extended release metformin (MET) on glycemic control in patients with type-2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or MET. This was a prospective, open-labeled, multicentric study over 12 weeks. Patients who were diagnosed with type-2 diabetes and were uncontrolled on monotherapy with single oral hypoglycemic agents such as glimepiride or MET and characterized by glycosylated hemoglobin (HbA1c) ≥7% and ≤10% and fasting plasma glucose (FPG) ≥ 140 mg/dL were enrolled in this study. Treatment regimen was started at 1 mg of glimepiride plus 500 mg of MET once a day and was titrated to next dose level depending on the clinician's judgment, not exceeding a total daily dose of 8 mg of glimepiride and 2000 mg of MET. After 12-weektreatment, glimepiride plus MET combination showed improvement in metabolic control as assessed by changes in HbA1c, FPG, and post prandial glucose (PPG). Primary efficacy parameter, HbA1c, was significantly reduced to (7.65 ± 1.70) at the end of the treatment from the baseline value (8.35 ± 0.93) (P < 0.001). Of the patients, 65.79% showed ≥0.5% reduction in HbA1c and or HbA1c <7% at the end of the therapy. FPG and PPG were significantly reduced at the end of the therapy as compared with baseline values (P < 0.001). Moreover, the lipid profile was also improved during the treatment period. The addition of glimepiride to MET is an effective treatment for patients inadequately controlled on sulfonylurea or Met alone. A combination of glimepiride with MET achieves good glycemic control with better tolerability profile.