Generation Sulfonylurea Research Articles

A comparative study of efficacy and safety of glimepiride versus gliclazide as an add on to metformin in Type 2 diabetes mellitus at a tertiary care hospital

Background: Type 2 diabetes mellitus (T2DM) is a chronic disorder with progressive pancreatic β-cell dysfunction and insulin resistance. Hyperglycemia associated with uncontrolled T2DM leads to various diabetes-related complications. Although metformin is the most preferred first-line drug, 5–10% of patients per year subsequently fail to achieve target HbA1c levels, subsequently requiring combination therapy. While efficacy and cost favor the use of sulfonylureas, hypoglycemic episodes limit its use. Newer generation sulfonylureas such as glimepiride and gliclazide are presumed to have lower incidence of hypoglycemia. Aims and Objectives: The aim of the study was to assess the efficacy and safety of glimepiride versus gliclazide as an add-on to metformin in T2DM. Materials and Methods: A total of 60 patients with T2DM (HbA1c 7.0–10.0%, on metformin monotherapy) were recruited and randomized into two groups of 30 cases each. Group A received glimepiride 2 mg as add-on to metformin 1500 mg and Group B received gliclazide 80 mg as add-on to metformin 1500 mg. HbA1c, lipid profile, body mass index, and total blood count were assessed at baseline and at the end 12 weeks of treatment. Fasting blood sugar (FBS) and post prandial blood sugar (PPBS) were assessed at the end of 4, 8, and 12 weeks and adverse events were assessed throughout the study period. Results: There was a significant decrease in HbA1c, FBS, and PPBS scores from baseline to the end of 12 weeks in both groups (P < 0.001), but the difference was not statistically significant between the two groups (P > 0.05). A significant decrease in lipid levels was observed in both groups except for high-density lipoprotein, low-density lipoprotein in the metformin + gliclazide group. The treatment was well tolerated in both groups, with the most common adverse events being nausea, diarrhea, and epigastric pain. Conclusion: Glimepiride and gliclazide are both equally effective as an add-on to metformin in improving glycaemic indices and are well tolerated in the management of uncontrolled T2DM.

An Update on the Molecular and Cellular Basis of Pharmacotherapy in Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is projected to reach 783 million in 2045. In 2021 alone, more than USD 966 billion was spent on the management of DM. Reduced physical activity due to urbanization is believed to be the major cause of the increase in the incidence of the disease, as it is associated with higher rates of obesity. Diabetes poses a risk for chronic complications such as nephropathy, angiopathy, neuropathy and retinopathy. Hence, the successful management of blood glucose is the cornerstone of DM therapy. The effective management of the hyperglycemia associated with type 2 diabetes includes physical exercise, diet and therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase inhibitors, sodium-glucose cotransporter-2 inhibitors and bile acid sequestrants). The optimal and timely treatment of DM improves the quality of life and reduces the severe burden of the disease for patients. Genetic testing, examining the roles of different genes involved in the pathogenesis of DM, may also help to achieve optimal DM management in the future by reducing the incidence of DM and by enhancing the use of individualized treatment regimens.

CHARACTERIZATION AND DISSOLUTION RATE STUDIES OF INCLUSION COMPLEX OF GLIBENCLAMIDE AND HYDROXYPROPYL-Β-CYCLODEXTRIN USING CO-GRINDING METHOD

Objective: Glibenclamide belongs to the 2nd generation sulfonylurea group as an oral antidiabetic with low solubility in water and high bioavailability in systemic circulation (Biopharmaceutical Classification System class II). This study aimed to increase the solubility and dissolution rate of glibenclamide by preparing an inclusion complex of Glibenclamide and Hydroxypropyl-β-cyclodextrin. Methods: Inclusion complexes were prepared by the co-grinding method in two ratios 1:1 and 1:2 mol. Characterizations of inclusion complex were carried out by Scanning Electron Microscopy (SEM), Fourier Transform Infrared (FT-IR) spectroscopy, Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) analysis. Solubility test was carried out in CO2-free distilled water and dissolution rate was carried out in phosphate buffer pH 7.4. Results: The results of the SEM analysis showed changes in particle morphology. FT-IR spectroscopy shows a shift in wavenumber. DSC analysis showed a decrease in the melting point of the inclusion complex. XRD characterization results showed a decrease in the intensity of the inclusion complex. Solubility of inclusion complex of glibenclamide increased nine times 1:1 mol inclusion complex, twelve times 1:2 mol inclusion complex compared to intact glibenclamide. The dissolution of glibenclamide, inclusion complex 1:1, and inclusion complex 1:2 in phosphate buffer pH 7.4 medium at 60 min was 17.19%, 34.15% and 52.83% respectively. Conclusion: Based on the results of the study, it can be said that the glibenclamide inclusion complex with Hydroxypropyl-β-cyclodextrin successfully increases the solubility and dissolution rate of glibenclamide significantly.

Implementation of factorial experimental design in chitosan - tripolyphosphate nanoparticles development by ionotropic gelation

Glimepiride (GM) is third generation sulfonylurea group and preferably used for the treatment of type -II diabetes mellitus. It belongs to BCS class II drugs according to biopharmaceutical classification system which shows low aqueous solubility. The purpose of this work was to develop and optimize glimepiride loaded chitosan- tripolyphosphate nanoparticles by ionotropic gelation method using 32 full factorial experimental designs. The developed chitosan nanoparticles were evaluated for particle size, zeta potential, entrapment efficiency, %yield and in vitro drug release etc. Factorial experimental design was implemented to optimize the independent variables like drug: polymer ratio (X1) and concentration of cross linking agent (X2) on dependent variables like particle size (Y1) and entrapment efficiency (Y2). A statistical analysis was performed using minitab 16 software with respect to ANOVA, regression analysis. The surface plots and contour plots represent the relationship between the experimental responses and the set of independent variables. The factorial experimental design was validated by checkpoint analysis and desirability function approach was applied for optimization of chitosan nanoparticle formulation. Drug entrapment efficiency and mean particle size of optimized formulation was found to be 61.25% and 222 nm respectively. Nanoparticles revealed initial burst release followed by slow drug release.

Glimepiride induced Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): A case report

The Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is an important cause of hyponatremia in hospitalized patients and can be caused by a variety of drugs. SIADH is a recognized side effect of 1st generation sulfonylurea (Chlorpropamide) due to its effect on vasopressin secretion. Here we described a 55-year-old woman with uncontrolled type 2 diabetes on glimepiride with SIADH presenting with anorexia, asthenia, and altered mental status. After the withdrawal of glimepiride, these symptoms were improved and sodium level returned to a normal value which demand monitoring of serum sodium level during treatment with glimepiride.

Комбинированная терапия «метформин + глимепирид» у больных сахарным диабетом 2-го типа (молекулярные механизмы оптимизации реабилитирующего действия)

Обзор посвящен описанию молекулярных механизмов терапевтического действия комбинации пероральных антидиабетических препаратов «метформин + глимепирид», направленного на коррекцию обоих дефектов, которые определяют развитие метаболических нарушений при сахарном диабете 2-го типа, а именно относительного дефицита инсулина и инсулинорезистентности. Сочетание метформина с глимепиридом оптимально в плане терапевтического воздействия на обе молекулы, недостаточная активность которых определяет метаболическое состояние инсулинорезистентности, соответственно аденозинмонофосфатактивируемую протеинкиназу и пролифератором пероксисом активированный рецептор γ. Кроме того, метформину присуща уникальная способность устранять феномен «гипергликемической памяти» за счет повышения экспрессии и активности сиртуина-1. С другой стороны, препарат сульфонилмочевины третьей генерации глимепирид обеспечивает «щадящую» стимуляцию β-клеток, что сохраняет физиологическое соотношение проинсулин/инсулин и замедляет развитие феномена десенситизации β-клеток к физиологическим и фармакологическим стимулам. Глимепирид сохраняет защитный феномен ишемического прекондиционирования и расширяет спектр терапевтического влияния на патофизиологические составляющие инсулинорезистентности за счет инсулинмиметического и инсулинсенситайзерного эффекта, а также потенцирует благоприятные эффекты метформина (в частности, через адипонектин). С этим связано достижение оптимизированной терапевтической эффективности фармкомбинации при снижении побочного действия (уменьшение дозы глимепирида, метформина).

Refractory Hypoglycemia Related to Gastric Bypass Complicated by Hypothyroidism

A 29-year-old African-American female was brought to the emergency department for sudden onset nausea, dizziness, and loss of consciousness at work. She was found to have low blood sugar and was fed with juice and crackers. She had history of similar episodes in the past, migraine headache, post-thyroidectomy hypothyroidism, seizures, generalized anxiety disorder, gastroesophageal reflux disease, and Roux-en-Y gastric bypass 9 months ago for morbid obesity related refractory Pseudotumor Cerebri (failed VP Shunting). She lost 41 kg, and had intolerance to foods from dumping syndrome. Her vital signs were within normal limits upon arrival to the ER. Laboratory parameters were remarkable for hypoglycemia of 52 mg/dL. She was immediately given dextrose intravenously. ECG showed sinus bradycardia. Though she regained consciousness, her blood sugar levels were persistently low, the lowest recording being 43 mg/dL. She was placed on a continuous D10 infusion. Further investigations revealed negative toxicology screens for 1st and 2nd generation sulfonylureas, and normal insulin levels at the time of the hypoglycemic event. Her TSH was found to be very high (99 nIU/mL). Her thyroglobulin (2.8 ng/mL), free T4 (0.25ng/dL), thyroglobulin antibody (99.18 uIU/mL), cortisol levels in morning (14.2 ug/mL), and evening (4.6 ug/dL) were found to be within normal range. Abdominal MRI did not reveal Insulinoma or any other pathology. Repeat ECG showed normal sinus rhythm with occasional PVCs. She was treated for nausea with ondansetron, promethazine, scopolamine, and dronabinol. Dextrose infusion was titrated down with rise in blood sugar levels. She confessed non-compliance to thyroid replacement. Therefore, she was initially treated with intravenous thyroxine replacement, which was later switched to oral therapy. Psychiatry evaluation ruled out any eating disorder. She was counselled to eat small frequent meals, increase dietary proteins, and restrict high glycemic index sugars. Educational value: National data indicates an increasing trend for admissions related to morbid obesity and bariatric procedures, especially laparoscopic (vertical) sleeve gastrectomy (see Fig 1). (1) Complex alteration in the signaling pathway to pancreas owing to changing metabolism causes hypoglycemia after bariatric surgery. When compounded by severe untreated hypothyroidism, as in our case, causes severe hypoglycemia needing hospitalization. Patient education for adjustment in dietary habits would have played a key role in preventing episodes of severe hypoglycemia.Reference:1.HCUPnet, Healthcare Cost and Utilization Project. Agency for Healthcare Research and Quality, Rockville, MD. https://hcupnet.ahrq.gov/.Fig 1: Trends for admissions for Morbid Obesity and Sleeve Gastrectomy

Development and Characterization of Glimepiride Novel Solid Nanodispersion for Improving Its Oral Bioavailability

Glimepiride is an antidiabetic drug which is one of the third generation sulfonylureas. It belongs to class II, according to the BCS (Biopharmaceutical Classification System), which is characterized by low solubility and high permeability. The aim of this work was to formulate glimepiride as solid dispersion using water-soluble carriers to enhance its aqueous solubility and thus enhance its bioavailability. Nine formulations of glimepiride solid dispersion were prepared by a solvent evaporation technique using three different carriers (mannitol, polyethylene glycol 6000, and β-cyclodextrin) with three different drug carrier ratio (1:1, 1:3, and 1:6). Formulation variables were optimized using 32 full factorial design. The prepared formulations were evaluated for production yield, drug content, micromeritic properties, thermal analysis, in-vitro release, and in-vivo hypoglycemic effect. All prepared formulations showed high production yield ranged from 98.4 ± 2.8 to 99.8 ± 2.2% and high drug content in the range of 97.2 ± 3.2 to 99.6 ± 2.1%. The micromeritic properties revealed that all prepared glimepiride formulations showed good flowability. The differential scanning calorimetry study revealed the presence of the drug in the more soluble amorphous form. In accordance with the results of in vitro release study, it was found that the solubility of glimepiride was increased by increasing the drug carrier ratio, compared with the pure form of the drug. It was found that F9 showed a high and rapid reduction in blood glucose levels in diabetic rats, which indicated the success of a solid dispersion technique in improving the solubility and hence the bioavailability of glimepiride.

Sulfonilureas, su uso actual en el tratamiento de la Diabetes Mellitus tipo 2

Se hace una revisión actual de las sulfonilureas como hipoglicemiantes orales en el tratamiento de la diabetes mellitus tipo 2, particularmente de las sulfonilureas de segunda y tercera generación; asi como de su mecanismo de acción, riesgo cardiovascular, sus efectos adversos y su recomendación según las guías de la ADA, AACE y ALAD y su indicación en pacientes infectados con COVID-19.

Optimization of Floating Tablet Containing Glibenclamide Using Simplex Lattice Design

Glibenclamide is a second generation sulfonyl ureas drug that are widely used in diabetes type 2 therapy. Glibenclamide in floating tablet formulations is used to improve the bioavailability. The aim of this study was to determine the optimum composition of floating tablets of glibenclamide by simplex lattice design. The tablets were prepared by wet granulation technique, using HPMC K100LV and Carbopol 940 as polimers. The optimum formula was determined based on numeric method with physical properties, floating characters, and dissolution profile of tablets. the results of the study show that glibenclamide floating tablets have good physicochemical properties. The combination of HPMC K100LV and Carbopol 940 decreases floating lag time and dissolution rate of floating glibenclamide tablets. The optimum composition of glibenclamide floating tablet was HPMC K100LV 44.29 mg and Carbopol 940 15.71 mg with desirability value 0.989.

Trigonella Foenum Graecum Extract Benefits on Hematological, Biochemical and Male Reproductive System of as a Complementary Therapy with Glimepiride in Treating Streptozotocin Induced Diabetic Rats

Diabetes mellitus (DM) is a chronic metabolic disorder. Streptozotocin is a naturally occurring cytotoxic chemical, particularly toxic to the pancreas and insulin producing beta cells in mammals and induces diabetes. Glimepiride is a second generation sulfonylurea, used as second-line or add-on treatment options for type 2 diabetes. Fenugreek (Trigonellafoenum graecum) seeds have been documented as a traditional plant treatment for diabetes. Soluble dietary fiber of Fenugreek significantly improved oral glucose tolerance in diabetic rats. It also exerts anti-diabetic effects mediated through the inhibition of carbohydrate digestion and absorption and the enhancement of peripheral insulin action. Most herbal remedies can interact with allopathic drugs resulting in altered activity and toxicity. At the same time, herbal remedies might produce the same kind of effects as the drug produce. Current published research information on herb-drug interactions is scanty. So, the aim of this study was to investigate the possible interaction between conventional drug used for the management of diabetes; (Glimepiride) and a traditional herbal remedy; Fenugreek aqueous extract in Streptozotocin induced diabetic male albino rats. In conclusion, combination therapy induces better hematological, biochemical effects and improves the oxidative stress biomarkers and antioxidant enzymes. Histological studies showed better results on some organ functions. The results emphasize the benefit of using the combination of Fenugreek seeds aqueous extracts as supportive complementary anti-diabetic therapy.

Impact of flucetosulfuron on weed seed bank in wet seeded rice

An experiment was conducted to assess the impact of flucetosulfuron, a new generation sulfonylurea herbicide, on weed seed bank dynamics of wet land paddy field. Field experiments were carried out during two consecutive seasons (Kharif 2016 and Rabi 2016-’17), to assess the bio-efficacy of flucetosulfuron in wet seeded rice which was accompanied by weed seed bank assay. Weed seed bank assay of the soil was carried out before and after the field experiments in both the seasons by the seedling emergence method. The experiment on weed seed bank was laid out in Completely Randomised Block Design (CRD) with 12 treatments replicated thrice. Flucetosulfuron @ 20, 25, and 30 g ha-1applied at 2-3, 10-12, and 18-20 days after sowing (DAS) along with two control treatments viz., hand weeding at 20 and 40 DAS and unweeded control comprised the treatments. The emerging weeds were uprooted at 14 days interval up to a period of two months; categorized as grasses, broad leaved weeds, and sedges and counted. Results revealed that non-herbicidal plots recorded significantly higher count of total emerged weeds compared to herbicide applied plots. In all the herbicide applied plots, effective reduction in weed seed bank could be obtained irrespective of the dose of the herbicide. Regarding the time of application, flucetosulfuron applied at 10-12 and 18-20 DAS recorded significantly lower weed seed bank during both the seasons, compared to its application at 2-3 DAS.

A Novel and Facile Process for the Synthesis of Gliclazide

Background: Gliclazide is a second generation sulfonyl urea which acts as hypoglycemic agent (oral antidiabetic agent). It improves the function of blood coagulation, has hypoglycemic effect, and thus has been widely used in clinical treatment. Several syntheses of Gliclazide have been reported, but all of them have some drawbacks. Therefore, there has been an ever-increasing interest in finding a novel route for Gliclazide using simple and easily commercial available chemicals. Methods: A Novel and facile process of preparing Gliclazide is herein reported which is comprised of three steps. Aryl haloformate was reacted with amino heterocyclic compound to give carbamate. The salt of p-toluene sulfonamide was prepared with metal hydroxide or metal alkoxide, and this salt of sulfonamide was then reacted with carbamate to give Gliclazide. Results: The carbamate produced from aryl haloformates was reacted with salt of p-toluene sulfonamide in the presence of base to produce Gliclazide with good yield and purity. The salt of p-toluene sulfonamide was prepared by two methods. In one method, salt was prepared using base at 100°C in polar aprotic solvent which was reacted with carbamate at 25°C to give Gliclazide. This method gives 70% yield of Gliclazide with purity above 99%. In another method, the salt of p-toluene sulfonamide was prepared at 100°C in polar aprotic solvent using base. The salt was isolated. The isolated salt of sulfonamide is stable at 25°C. This salt was reacted with carbamate at 25°C to give Gliclazide. This method gives 64% yield of Gliclazide with purity above 99%. The various solvents, bases were tested in this investigation. It was observed that excellent yield of the product was obtained when the reaction was carried out by using DMSO as solvent and potassium tert-butoxide as base. Conclusion: In conclusion, we have developed new and effective process for the synthesis of Gliclazide via condensation of sulfonamide with various carbamates using a less expensive aryl haloformates with good yield and purity. Keywords: Gliclazide, sulfonyl urea, hypoglycemic agent, carbamate, p-toluene sulfonamide, metal alkoxide/hydroxide.

The Real-Life Effectiveness and Care Patterns of Diabetes Management Study for Balkan Region (Slovenia, Croatia, Serbia, Bulgaria): A Multicenter, Observational, Cross-Sectional Study.

IntroductionRecent large randomized controlled trials highlighted the clinical significance of hypoglycemic episodes in the treatment of diabetes. The present survey was conducted to provide information from real-life practice on the incidence of hypoglycemia in type 2 diabetic patients treated with sulfonylureas.MethodsThis multicenter, observational, cross-sectional study collected data on incidence of side effects of sulfonylurea-based therapy in type 2 diabetic patients in four countries of the Balkan region (Slovenia, Croatia, Serbia, Bulgaria) from October 2014 to June 2015.ResultsOf the 608 who participated in the study, 573 patients (mean age 67.2 years, mean body mass index 29.9 kg/m2) met the inclusion/exclusion criteria. More than 90% of the patients were treated with the newer generation sulfonylureas—gliclazide or glimepiride—either as monotherapy or as dual therapy in combination with metformin. In total, 210 patients (36.6%) reported hypoglycemic episode(s) in the last 6 months. Mild episodes were reported by 132 patients (62.8%), moderate by 66 (31.2%), severe by 8 patients (4.0%), and very severe by 4 patients (2%), respectively. Overall, 171 patients (28.2%) reported body weight increase during the previous year. The mean reported body weight gain in this group of patients was 4.2 kg (SD 2.7, median 3). Among them, 68.1% gained less than 5 kg, 25.0% gained 5–9 kg, and the rest gained more than 10 kg.ConclusionAlthough newer generation sulfonylureas are generally considered safe in terms of hypoglycemia, our data indicates their use is associated with substantial risk of hypoglycemia and weight gain. Clinicians should be mindful of these findings when prescribing SUs and inform patients about the risk of hypoglycemia.FundingMerck Sharp & Dohme.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0288-x) contains supplementary material, which is available to authorized users.

Metabolomic analysis of healthy human urine following administration of glimepiride using a liquid chromatography-tandem mass spectrometry.

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.

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.

Impact of hypoglycemic events and HbA1c level on sulfonylurea discontinuation and down-titration

ABSTRACTBackground: A retrospective cohort study using GE Centricity electronic medical records assessed the association between post-index hypoglycemia and HbA1c with discontinuation and down-titration of sulfonylureas among patients with Type 2 diabetes mellitus.Methods: Adult patients with an index prescription for a sulfonylurea and ≥12 months’ continuous records pre- and post-index were eligible. Sulfonylurea discontinuation and down-titration was assessed 1-year post-index. Discontinuation occurred if the date of a prescription was >90 days from the preceding prescription plus days of supply. Down-titration occurred when a subsequent prescription was lower than the index dose. Cox regression assessed the association between post-index hypoglycemia and HbA1c with time to sulfonylurea discontinuation and down-titration, as well as other factors.Results: 28,371 participants were included in the study; 13,459 (47.4%) were discontinuers, 717 (2.5%) were down-titraters, and 14,195 (50.0%) were continuers. 0.6% of continuers experienced hypoglycemia 1-year post-index, compared with 3.1% of down-titraters and 0.8% of discontinuers (p < 0.0001). Patients with post-index hypoglycemia had a significantly higher rate of discontinuation (hazard ratio [HR] = 1.82, 95% CI: 1.47–2.23) and down-titration (HR = 4.25, 95% CI: 1.92–8.03). Patients with higher post-index HbA1c and use of 2nd generation sulfonylureas had an increased rate of discontinuation (HR = 1.05, 95% CI: 1.04–1.06; HR = 1.19, 95% CI: 1.14–1.24, respectively).Conclusion: Approximately half of participants who initiated sulfonylureas discontinued or down-titrated therapy within one year. Both post-index hypoglycemia and higher HbA1c were significant risk factors for sulfonylurea treatment change.

Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas

Objectives: Sulfonylurea therapy among patients with type 2 diabetes mellitus (T2DM) can be disrupted due to adverse events, including hypoglycemia. A retrospective study using the MarketScan claims database quantified the frequency of sulfonylurea discontinuation or down-titration and identified associated risk factors.Research design and methods: Adult patients with an index sulfonylurea prescription between 2008 and 2012 and 1 year continuous enrollment pre- and post-index were included. Therapy changes assessed over 1 year post-index included discontinuation and down-titration. Discontinuation occurred if the date of a fill was >90 days from the end date of the preceding fill. Down-titration occurred when a fill had a lower equivalent dose than the fill on the index date. Kaplan–Meier methods estimated the probability of either discontinuation or down-titration over 12 months, and Cox regression models identified associated risk factors.Results: A total of 104,082 sulfonylurea users were included in the study and the probability of either discontinuation or down-titration at 3, 6 and 12 months was 23.2%, 38.9%, and 52.3%, respectively. Major risk factors associated with therapy changes included post-index hypoglycemia (discontinuation hazard ratio [HR] = 1.78 [1.68, 1.89]; down-titration HR =2.79 [2.40, 3.23]) and concomitant use of insulin (discontinuation HR =1.48 [1.40, 1.57]; down-titration HR =1.82 [1.56, 2.11]). Other risk factors included younger age, female gender, use of second generation sulfonylureas, prior cardiovascular comorbidity and liver disease.Limitations: The study was not able to assess unreported, potentially mild cases of hypoglycemia, nor was it able to evaluate the association between changes in therapy and HbA1c levels or body weight.Conclusions: More than half of T2DM patients who initiated sulfonylurea therapy discontinued or down-titrated within 1 year. Insulin use and hypoglycemia were associated with sulfonylurea therapy change.

Pharmacokinetics, efficacy and safety of glyburide for treatment of gestational diabetes mellitus

ABSTRACTIntroduction: Gestational diabetes mellitus (GDM) complicates 10% of all pregnancies and is defined as hyperglycemia first noted during pregnancy. Rates of GDM are rising and untreated GDM results in complications for both mother and fetus. GDM is often managed by diet and exercise but 30–40% of women will require pharmacological intervention. Insulin has traditionally been the treatment of choice but since 2007, glyburide, a second generation sulfonylurea has become the most prescribed medication for GDM.Areas covered: This review will cover the pharmacokinetics, efficacy, and safety of glyburide for the management of GDM.Expert opinion: Management of GDM is challenging secondary to the stringent glycemic goals that mimic the lower glucose levels in pregnancy. Glyburide is generally effective in treating hyperglycemia. However, several studies have raised safety concerns showing higher neonatal intensive care unit (NICU) admissions, higher rates of macrosomia, large for gestational age and pre-eclampsia in the mother. For this reason, insulin should be first-line therapy for GDM. In areas of limited resources where the self-monitoring needed for accurate insulin dosing is not possible, where access to refrigeration for insulin storage is not universal, or severe needle phobia then the benefits of glyburide (controlling hyperglycemia) outweighs the harm of NICU admissions and macrosomia.

The features of sulfonylurea’s usе in the general practice: a systematic review of glimepiride researches

Diabetes mellitus (DM) is on the third place by the prevalence after cardiovascular and oncologic diseases in the world. The choice of drug treatment DM is a complex process in the general practice. Background: identify the features of use, pharmacocinetics and pharmacodynamics of glimepiride in patients with DM type 2 in the general practice. A systematic review of publications in JAMA, Scholar and PubMed, as well as in journals and conference publications from 2005 till 2015 was conducted. It was found, that glimepiride, as a drug of 3rd generation sulfonylurea, has hypoglycemic, antiatherosclerotic, antiatherogenic, anti-inflammatory, antiapoptotic, antiaggregatory effects. High safety of glimepiride was proved by lower risk of severe and hidden hipoglycemia, positive results of use in patients with concomitant cardiovascular pathology. Proved high efficiency and safety of glimepiride as monotherapy and in combination allows its wide use in general practice