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Background: Antidiabetic drugs are widely used in clinical practice as essential drugs for the treatment of diabetes. The effect of hypoglycemic drugs on erectile dysfunction has not been fully proven due to the presence of multiple confounding factors. Methods: Two-sample Mendelian randomization (TSMR) was used to examine the causal effect of antidiabetic drugs (including metformin, insulin and gliclazide) on erectile dysfunction. We used five robust analytic methods, of which the inverse variance weighting (IVW) method was the primary method, and also assessed factors such as sensitivity, pleiotropy, and heterogeneity. Effect statistics for exposures and outcomes were downloaded from publicly available data sets, including open Genome-Wide Association Studies (GWAS) and the UK Biobank (UKB). Results: In some of the hypoglycemic drug use, there was a significant causal relationship between metformin use and erectile dysfunction [Beta: 4.9386; OR:1.396E+02 (95% CI:9.13-2135); p-value: 0.0004), suggesting that metformin increased the risk of erectile dysfunction development. Also, we saw that gliclazide use also increased the risk of erectile dysfunction [Beta: 11.7187; OR:0.0125 (95% CI:12.44-1.21E+09); P value: 0.0125). There was no significant causal relationship between insulin use and erectile dysfunction [Beta: 3.0730; OR:21.6071 (95% CI:0.24-1942.38); p-value: 0.1806). Leave-one-out, MR-Egger, and MR-PRESSO analyses produced consistent results. Conclusion: The use of metformin and gliclazide have the potential to increase the risk of erectile dysfunction. There is no causal relationship between the use of insulin and erectile dysfunction. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims/Introduction Materials and Methods Results Conclusions The study aim was to investigate sulfonylurea prescription patterns in elderly patients (age ≥65 years) with type 2 diabetes mellitus in Japan. Sulfonylurea use among older adults has been insufficiently examined, despite the associated risks of hypoglycemia.This retrospective cross‐sectional survey entailed analysis of Japanese pharmacy data, extracted from the Musubi database, for patients (age 20–100 years) prescribed sulfonylureas between November 2022 and October 2023. Dose distribution, adherence to the Diabetes Treatment Guidelines for the Elderly 2023 and coprescription of other diabetes medications were investigated.Of the total 91,229 patients, 80.1% were prescribed glimepiride, 16.3% gliclazide and 3.6% glibenclamide. In patients aged ≥65 years, exceeding the recommended dose (>1 mg/day for glimepiride, >40 mg/day for gliclazide) was numerically higher for glimepiride (25.0%) than for gliclazide (7.8%). The most common prescribing patterns were quadruple therapy with a sulfonylurea, a dipeptidyl peptidase‐4 inhibitor, an sodium–glucose transporter 2 inhibitor and a biguanide in patients aged 65 to <75 years, and dual therapy with a sulfonylurea and a dipeptidyl peptidase‐4 inhibitor in patients aged ≥75 years. Unfortunately, glinide was coprescribed for 338 (0.5%) of elderly patients. Insulin was coprescribed for 3,682 (5.6%) of elderly patients.Analysis of real‐world sulfonylurea prescription data found guideline non‐adherence, namely, excessive prescription of glimepiride, use of glibenclamide in elderly patients, and common coprescription with dipeptidyl peptidase‐4 inhibitors. These findings might provide an opportunity to reconsider the treatment of patients with type 2 diabetes mellitus who are over‐prescribed sulfonylureas to reduce residual risks, such as hypoglycemia. [ABSTRACT FROM AUTHOR]

The appropriate design of experiments (DoE) could support post-approval lean-stability approaches. A three-factor three-level face-centered design was constructed to evaluate the long-term stability of gliclazide (GLZ) alginate-gelatin beads. The formulation variables were GLZ%(X 1), alginate:gelatin ratio(X 2), and glutaraldehyde%(X 3). The studied responses included GLZ release at predefined intervals in 0.1 N HCl (2 h) followed by phosphate buffer (pH 7.4). Model-dependent and independent approaches were utilized for comparison. DoE-model validation and reduction were implemented. All the studied formulations showed non-significant changes in the particle size (p > 0.05) and most of them showed similar release profiles before and after storage. The directions of the relationships between the factors' main effects and the responses (Y 1 :Q 0.5 h , Y 2 :Q 2h, and Y 3 :Q 4h) remained unchanged after storage. The optimal factor settings based on the proposed optimization criteria were defined. The optimized formulations (OP-1 and OP-2) showed non-significant changes in the particle size after storage. The release profiles and kinetics of OP-1 and OP-2 remained unchanged after storage. No chemical change was indicated (FT-IR). DSC-thermograms of OP-1 indicated GLZ conversion to a more stable polymorph after storage. While OP-2 showed a change in GLZ crystallinity. The stored and fresh beads' surfaces after GLZ release were almost similar. DoE could be utilized to evaluate, optimize, and predict the effects of different formulation variables on the long-term stability of GLZ alginate-gelatin beads. [Display omitted] [ABSTRACT FROM AUTHOR]

The increasing burden of type 2 diabetes (T2D), in relation to alarming rise in the prevalence; challenges in the diagnosis, prevention, and treatment; as well as the substantial impact of disease on longevity and quality of life, is a major concern in healthcare worldwide. Sulfonylureas (SUs) have been a cornerstone of T2D pharmacotherapy for over 60 years as oral antidiabetic drugs (OADs), while the newer generation SUs, such as gliclazide modified release (MR), are known to be associated with low risk of hypoglycemia in addition to the cardiovascular neutrality. This scoping review aimed to specifically address the current position of gliclazide MR among other SUs in the contemporary treatment paradigm for T2D and to provide a practical guidance document to assist clinicians in using gliclazide MR in real-life clinical practice. The main topics addressed in this paper include the role of early and sustained glycemic control and use of SUs in T2D management, the properties of gliclazide MR in relation to its effectiveness and safety, the use of gliclazide therapy in special populations, and the place of SUs as a class and gliclazide MR specifically in the current T2D treatment algorithm. [ABSTRACT FROM AUTHOR]

Context Low-dose sulfonylureas (SUs) have been found to augment the classical incretin effect, increase glucose sensitivity and late phase incretin potentiation. Objective To evaluate potential synergy between low-dose SU plus a dipeptidyl peptidase 4 (DPP4) inhibitor. Methods Unblinded randomized crossover study at the Clinical Research Centre, University of Dundee. Thirty participants with T2DM (HbA1c < 64 mmol/mol) were treated with diet or metformin. Participants completed 4, 14-day blocks in a random order: control, gliclazide 20 mg (SU), sitagliptin 100 mg (DPP4 inhibitor [DPP4i]), or combination (SUDPP4i). A mixed meal test was conducted after each intervention. The primary outcome was the effect of treatment on beta-cell glucose sensitivity. Secondary outcomes included frequency of glucose <3 mmol/L on continuous glucose monitoring, subanalyses by genotype (KNCJ11 E23K), gender, and body mass index. Results SU combination with DPP4i showed additive effect on glucose lowering: mean glucose area under the curve (mean 95% CI) (mmol/L) was control 11.5 (10.7-12.3), DPP4i 10.2 (9.4-11.1), SU 9.7 (8.9-10.5), SUDPP4i 8.7 (7.9-9.5) (P <.001). Glucose sensitivity mirrored the additive effect (pmol min−1 m−2 mM−1): control 71.5 (51.1-91.9), DPP4i 75.9 (55.7-96.0), SU 86.3 (66.1-106.4), SUDPP4i 94.1 (73.9-114.3) (P =.04). The additive effect was seen in men but not women. Glucose time in range <3 mmol/L on continuous glucose monitoring (%) was unaffected: control 1 (2-4), DPP4i 2 (3-6), SU 1 (0-4), SUDPP4i 3 (2-7) (P =.65). Conclusion Low-dose sulfonylurea plus DPP4i has a potent glucose-lowering effect through augmentation of beta-cell function. A double-blind randomized controlled trial would formalize efficacy and safety of this combination, which may avoid negative aspects of SU. [ABSTRACT FROM AUTHOR]

Enhancement of oxidative stress and resultant neuronal injury play important roles in initiating cognitive impairment during the aging process. Thus, attenuating oxidative injury is regarded as a profitable therapeutic strategy for age-associated cognitive impairment. Previous studies showed that gliclazide (Gli) had a protective role in neuronal injury from cerebral ischemia/reperfusion (I/R) injury. However, whether Gli has a profitable effect on age-associated cognitive impairment remains largely unclear. The present study showed that Gli held the potential to attenuate neuronal apoptosis in D-gal-induced senescent cells and aging mice. Additionally, Gli could alleviate synaptic injury and cognitive function in D-gal-induced aging mice. Further study showed that Gli could attenuate oxidative stress in D-gal-induced senescent cells and aging mice. The p38 MAPK pathway was predicted as the downstream target of Gli retarding oxidative stress using in silico analysis. Further studies revealed that Gli attenuated D-gal-induced phosphorylation of p38 and facilitated Nrf2 nuclear expression, indicating that the anti-oxidative property of Gli may be associated with the p38 MAPK pathway. The study demonstrates that Gli has a beneficial effect on ameliorating D-gal-induced neuronal injury and cognitive impairment, making this compound a promising agent for the prevention and treatment of age-associated cognitive impairment. [ABSTRACT FROM AUTHOR]

UV Spectrophotometric method has been developed to determine Gliclazide in bulk pure and tablet forms. It is a simple, accurate, reproducible, rapid and less time-consuming method. The maximum wavelength of the drug was found to be 232nm. Beer Lamberts' law was obeyed in the concentration range of 2-20 µg/ml. (LOD)The limit of detection and limit of qualification (LOQ) was found to be 0.16 µg/ml and 0.50 µg/ml from this method per cent recovery of the drug was found to be 99.30% which indicates no interaction of the excipients. This method was found accurate, simple, precise and rapid for determination of tablet dosage form. [ABSTRACT FROM AUTHOR]

Sulfonylurea (SU) are an effective class of oral hypoglycemic drugs that have been used in clinical practice for more than 70 years. Despite the common mechanism of action, members of the class have significant intraclass differences in hypoglycemic activity, safety, and the presence of extrapancreatic effects. This review examines the features of gliclazide modified release (MR), its differences from other representatives of the SU and its place in modern recommendations for the treatment of type 2 diabetes mellitus. Gliclazide MR belongs to the modern 2nd generation SU with high hypoglycemic activity, low risk of hypoglycemia due to reversible binding to the SUR1 receptor and no effect on the Epac2 pathway, generally neutral effect on weight, proven nephroprotective properties and cardiovascular safety, which makes it possible to highlight it among representatives of the SU class. International and national clinical guidelines indicate the place of SU when it is necessary to intensify glucose-lowering therapy and glycemic control in patients with type 2 diabetes mellitus.

Background and objective: Poorly water-soluble dugs provide less dissolution rate and bioavailability; hence, it minimizes the pharmacological effect of orally administered medications. Gliclazide is a sulfonylurea antidiabetic medication of the second generation, used to treat type II diabetes mellitus. It belongs to the class II drugs of biopharmaceutic classification system, indicating that it has high permeability and poor aqueous solubility. The aim of this study is to determine an optimum solid dispersion method and drug to carrier ratio to improve the solubility of gliclazide. Methods: Solid dispersions of gliclazide were formulated with polyvinyl pyrrolidone K30 using various drug to carrier ratios (1:1, 1:3, and 1:5) by utilizing kneading and solvent evaporation methods. Solubility and dissolution rate of solid dispersion formulas were compared with pure drug and co-ground mixtures. The formulations were further evaluated in terms of percentage of yield, drug content, FTIR, SEM, DSC, and XRD studies. Results: The highest solubility improvement of gliclazide was obtained at the ratio 1:5 of gliclazide and PVP K30 utilizing solvent evaporation method, solubility increased about 2.54 folds (98.299 ± 5.77 µg/ml) as compared to pure gliclazide (38.739 µg/ml). Meanwhile, the greatest improvement in gliclazide dissolution rate was observed in the same solid dispersion formula that was about 105.76 % after 30 minutes. FTIR demonstrated no unwanted interaction between the drug and carrier. While, SEM, DSC, and XRD showed crystallinity of the drug was minimized and converted to amorphous form in solid dispersion formula. Conclusion: Based on the investigations of this study, it can be concluded that the drug to carrier weight ratios and preparation methods had the influence on the drug solubility and the release rate. The obtained data revealed that the solvent evaporation is the best method of solid dispersion for enhancing gliclazide solubility using PVP K30 with the ratio 1:5 of the drug and carrier.

More than 4.3 million people in the UK have been diagnosed with diabetes and there are thought to be a further 850 000 people living with diabetes who have not yet been diagnosed (Diabetes UK, 2024). Around half of all adults who have diabetes experience bladder dysfunction. It is one of the most common complications of diabetes, yet there is little in the medical literature and it is often unrecognised and poorly treated (Wittig et al, 2019). This article uses a case history approach to examine how diabetes can affect the bladder. [ABSTRACT FROM AUTHOR]

The use of herbal supplements, along with antidiabetic drugs, is common for better management of blood glucose levels in type II diabetes. Resveratrol, an herbal isolate, offers numerous benefits for managing diabetes and its complications. Gliclazide is a widely used medication for type II diabetes treatment. The present study was undertaken to determine the potential for interactions between resveratrol and gliclazide based on the relationship between herbal supplements and diabetes. The influence of resveratrol on the activity of gliclazide was determined by conducting single and multiple dose interaction studies in animal models. Blood samples collected at predetermined time intervals from experimental animals were used for the estimation of glucose and insulin levels. Additionally, serum gliclazide levels in rabbits were analysed by high-performance liquid chromatography. Gliclazide alone showed peak reductions in blood glucose levels at 2nd and 8th h after administration in rats and after 3 h in rabbits. In studies involving both single and multiple dose combinations of resveratrol with gliclazide, significant changes were observed in the amount of blood glucose reduction in normal rats, diabetic rats and normal rabbits. Additionally, this combination significantly altered the levels of insulin in the blood. Resveratrol affected the pharmacokinetics of gliclazide in rabbits. Overall, the effects of resveratrol on gliclazide were both related to pharmacokinetic and pharmacodynamic effects. Therefore, when prescribing gliclazide to patients who are using herbal preparations containing resveratrol, it is important to monitor glucose levels closely and adjust the dosage as needed. [ABSTRACT FROM AUTHOR]

A novel organic–inorganic gliclazide-loaded composite bead was developed by an ionic gelation process using acidified CaCl2, chitosan and tetraethylorthosilicate (TEOS) as a crosslinker. The beads were manufactured by crosslinking an inorganic silicone elastomer (-OH terminated polydimethylsiloxane, PDMS) with TEOS at different ratios before grafting onto an organic backbone (Na-alginate) using a 32 factorial experimental design. Gliclazide's encapsulation efficiency (EE%) and drug release over 8 h (% DR 8 h) were set as dependent responses for the optimisation of a pharmaceutical formula (herein referred to as 'G op') by response surface methodology. EE % and %DR 8 h of G op were 93.48% ± 0.19 and 70.29% ± 0.18, respectively. G op exhibited a controlled release of gliclazide that follows the Korsmeyer–Peppas kinetic model (R2 = 0.95) with super case II transport and pH-dependent swelling behaviour. In vitro testing of G op showed 92.17% ± 1.18 cell viability upon testing on C2C12 myoblasts, indicating the compatibility of this novel biomaterial platform with skeletal muscle drug delivery. [ABSTRACT FROM AUTHOR]

Purpose: Gliclazide (GLC)-loaded Aerosil 380 solid dispersion (GA-SD)-based tablets with co-processed excipient composites were formulated to critically evaluate the physicochemical performance of the resulting tablets with enhanced drug release. Methods: GA-SD was prepared using the solvent evaporation method with a 1:1 weight ratio based on a previously published report, and its drug release patterns were evaluated. Processed excipient composites, such as lactose-starch-povidone (LSP) and lactose-starch-povidone-sodium starch glycolate (LSPS), were prepared via a coprocessing strategy and evaluated for their ability to perform specific functions. At predetermined combination levels, aqueous dispersions of primary excipients were physically agglomerated at a controlled temperature below the gelatinization temperature (55 °C) before drying at 60 °C for 48 h. GA-SD and co-processed excipients (LSP and LSPS) were utilized to produce tablet batches GAC1 to GAC8 (Gliclazide-Aerosil 380–co-processed excipients, GAC) by direct compression. Through rigorous testing of tablet batches, the physicochemical properties of the resulting formulations were analyzed and compared to those of leading marketed formulations (MFs). FTIR studies were also conducted to detect drug-excipient interactions in the tablet formulations. The release mechanism of the GLC was determined by studying the dissolution process with various kinetic models. The GAC tablets were subjected to 40 °C/75% RH for 3 months to assess stability. Results: All tablet formulations of GA-SD containing co-processed excipients met the weight, friability, disintegration time, mechanical strength, and homogeneity requirements. There was significantly more GLC released from the GAC formulations (p < 0.05) at each time point when the formulations were exposed to water than when the formulations were exposed to MFs. In vitro, testing revealed that the GAC5 to GAC8 formulations were the most efficient due to the presence of the superdisintegrant in the LSPS composite, which may be a contributing factor to the improvement in the dissolution rate by GA-SD. FTIR analysis revealed no notable chemical interactions between GLC and the excipients in the solid state. The Korsmeyer-Peppas model was the best-fit kinetic model, indicating that diffusion is the predominant mechanism of GLC dissolution. According to the commercial standards, the GAC tablets maintained an acceptable hardness, disintegration time, and drug content during the stability studies. Additionally, no significant changes in release profiles were observed in the selected batches (p < 0.05). Conclusion: Compared with currently marketed formulations (MFs), GA-SD tablet formulations with co-processed excipients significantly improved the physicochemical properties, including the drug release rate. These findings could lead to the development of more effective and efficient tablet solid dosage forms of drugs with low water solubility, and co-processed excipients could be utilized as a more effective alternative to direct compression materials in tablet formulations. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (β = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (β = 1.414; se = 0.460; P = 2.118*10−3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (β = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (β = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes. [ABSTRACT FROM AUTHOR]

Background and Purpose: In alloxan-induced diabetic rats, this study sought to evaluate the hypoglycemic potential of the hydroalcoholic seed extract of Areca catechu, also referred to as areca nut, both as a stand-alone treatment and in combination with the diabetic drug gliclazide. Materials and Methods: The hot percolation method was used to produce the hydroalcoholic seed extract of A. catechu. Rats were given alloxan monohydrate and developed type II diabetes. The hydroalcoholic seed extract of A. catechu (1000 mg/kg p.o.) alone or in different combinations of gliclazide (25 mg/kg p.o.) and A. catechu extract (250, 500, and 1000 mg/kg p.o.) were administered to the six diabetic rats. Body weights and blood glucose levels were measured on days 7, 14, 21, and 28 of the treatment. On the 28th day, the kidney, liver, and pancreas underwent histological investigations in addition to an oral glucose tolerance test (OGTT). Results: Blood glucose levels were significantly lowered upon administration of A. catechu's hydroalcoholic seed extract, both alone and in conjunction with gliclazide. Comparing the diabetic control group to the A. catechu extract-treated group, histopathological examinations showed that high amounts of the extract, either by itself or in conjunction with gliclazide, caused the active proliferation of pancreatic beta cells, protecting against damage to the liver and kidneys. Conclusion: The hydroalcoholic seed extract of A. catechu showed promise as a monotherapy for controlling blood glucose levels, and as a co-administer for gliclazide, it showed signs of hypoglycemia. These results indicate A. catechu's possible therapeutic benefit as an adjuvant diabetic treatment. To investigate the underlying mechanisms of action and evaluate its safety and effectiveness in clinical settings, more study is necessary. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of gliclazide (GLZ) on intestinal mucosal barrier function in rats with ulcerative colitis (UC) by regulating advanced glycation end-products (AGEs) and their receptor for advanced glyca‐ tion end-products (RAGE). Methods The UC rat model was established by using trinitrobenzene sulfonic acid and alco‐ hol enema. They were randomly divided into the blank group, UC group, GLZ group (10 mg/kg GLZ), GLZ + empty vec‐ tor group (10 mg/kg GLZ + 0. 15 µL lentiviral empty vector), and GLZ + RAGE overexpression group (10 mg/kg GLZ+ 0. 15 µL RAGE overexpression lentiviral vector). After the intervention, the general conditions of the rats in each group were observed, the body weight was measured, and disease activity index (DAI) score was performed. Blood samples were collected and the levels of diamine oxidase (DAO) and D-lactic acid (D-LA) in serum were detected. Colon tissue was se‐ lected and the pathological damage score was performed. Myeloperoxidase (MPO) activity, and the protein expression lev‐ els of AGE, RAGE, phosphorylated nuclear transcription factor p65(p-NF-κB p65) and NF-κB p65 were determined. Results Compared with the blank group, the DAI and colon histopathological scores increased, the levels of DAO and DLA in serum increased, MPO activity, and the expression levels of RAGE, AGE, and p-NF-κB p65/NF-κB p65 increased in the UC group. Compared with the UC group, the DAI and pathological scores, the levels of DAO and D-LA in serum, MPO activity, the expression levels of RAGE, AGE, and p-NF-κB p65/NF-κB p65 decreased in the GLZ group and the GLZ+empty vector group. Compared with the GLZ+empty vector group, the DAI and pathological scores, the level of DAO and D-LA in serum, MPO activity, the expression levels of RAGE, AGE, and p-NF-κB p65/NF-κB p65 increased in the GLZ+RAGE overexpression group. The differences between the above observation groups were statistically significant (all P<0. 05). Conclusion GLZ can improve the symptoms of pathological injury in UC rats and protect the intestinal mucosal barrier function, which may be related to the inhibition of AGE/RAGE signaling pathway [ABSTRACT FROM AUTHOR]

Background: Gliclazide is a potential anti-cancer drug candidate for preventing carcinogenesis. However, the effect of gliclazide on colitis-associated colorectal cancer remains unknown. Aims: We aimed to evaluate whether gliclazide plays a protective role in colitis-associated colorectal cancer and the underlying molecular mechanism. Methods: The administration of azoxymethane (AOM) followed by dextran sulfate sodium (DSS) aimed to induce colitis-associated colorectal cancer in mice. C57BL mice were gavaged with gliclazide (6 mg/kg by gavage 5 days a week) for 12 weeks immediately following AOM administration. After sacrificing the mice, colon tissues were measured for tumor number and tumor burden. The proliferation- and inflammation-related molecular mechanisms were explored. Results: The administration of gliclazide significantly reduced the tumor number and tumor burden in mice. Cell proliferation decreased in the gliclazide group compared with the control group, as indicated by reduced Ki-67 expression. Furthermore, gliclazide alleviated colonic inflammation, significantly decreased pro-inflammatory factor TNF-α levels and increased anti-inflammatory factor IL-10 levels in vivo. In vivo and vitro, it was shown that gliclazide increased the level of phospho-AMPK (p-AMPK) and inhibited NF-κB activity. Further studies demonstrated that the inhibition of NF-κB activity induced by gliclazide was mediated by p-AMPK in vitro. Conclusions: Gliclazide effectively alleviated colonic inflammation and prevented colonic carcinogenesis in an AOM–DSS mouse model by modulating the AMPK-NF-κB signaling pathway. Thus, gliclazide holds potential as a chemopreventive agent for colitis-associated colorectal cancer. [ABSTRACT FROM AUTHOR]

Oxidative stress, endoplasmic reticulum stress, and inflammation are implicated in both pathogenesis and progression of type 2 diabetes. This study aimed to compare the effects of metformin and gliclazide on endoplasmic reticulum stress, oxidative stress, and inflammation in the liver and pancreas of type 2 diabetic rats. Twenty Wistar rats (180–200 g) were arbitrarily allocated to four groups containing five animals each. Group 1 was the normal control and was administered the vehicle (distilled water) while the study lasted. Groups 2 and 3 contained diabetic rats and were treated with metformin (100 mg/kg) and gliclazide (50 mg/kg), respectively, through oral gavage. Group 4 was the diabetic control and contained diabetic animals administered distilled water throughout the study. Experimental animals were made diabetic by a single intraperitoneal injection of 40 mg/kg streptozotocin subsequent to the administration of 10% fructose for 2 weeks. Treatment lasted for 28 days, after which experimental animals were sacrificed. The liver and pancreas were rapidly excised and stored at −20 °C until used. Polymerase chain reaction was used to evaluate the expression of activating transcription factor-6 (ATF6), C/EBP homologous protein (CHOP), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) in the tissues. Results showed that both metformin and gliclazide substantially ameliorated stress as indicated by reduced expression of ATF6, CHOP, Nrf2 and NF-κB in the selected tissues. There was no clear-cut difference in the stress-ameliorating effects of metformin and gliclazide. [ABSTRACT FROM AUTHOR]

Objective: In this study, the effects of gliclazides, a second generation sulfonylurea group, on BDNF and NGF plasma levels, which are considered neurodegeneration biomarkers, will be examined. When designing our study, we assumed that gliazides might have positive neuronal effects. Thus, the possible positive effects of gliclazide will be emphasized in our study. Methods: In the experiment, 21 adult male Wistar-Albino rats were used. Serum BDNF and NGF levels were determined by analyzing with enzyme-linked immunosorbent assay kit in accordance with the recommendations. Results: BDNF levels were significantly lower in gliclazide-treated diabetic rats and nonmedicated diabetic rats compared to the healthy control group (p=0.017, p<0.001, respectively). Although the BDNF level of rats with diabetes given gliclazide was increased compared to rats with and without diabetes, this difference was not significant (p=0.107). Similarly, NGF levels were significantly lower in rats given gliclazide (p=0.009) and diabetic rats not given gliclazide (p=0.001) compared to the healthy control group. When the diabetic groups were compared among themselves, although the NGF level was increased in the gliclazide group, this difference was not statistically significant (p=0.638). The differences between the groups were significant in cyclic AMP regulatory element binding (p<0.001), c-FOS (p<0.001), amyloid precursor protein (p<0.001), B-SECRETASE1 (p=0.004), and doublecortin (p<0.001) levels. Conclusion: As a result, serum BDNF and NGF levels were significantly higher in non-diabetic healthy control group rats than in diabetic rats. While low serum levels of BDNF and NGF neurotrophins, which increase in neurodegeneration, were observed in diabetic rats, this level was observed to be higher in diabetic rats given gliclazide. [ABSTRACT FROM AUTHOR]

Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as "safe and smart" choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers' knowledge of the management of T2DM, leading to superior patient outcomes. [ABSTRACT FROM AUTHOR]

The present investigation aims to develop and evaluate a radiopharmaceutical for targeting and assessing β-cells mass based on gliclazide, an antidiabetic drug that specifically binds the sulfonylurea receptor unique to the β-cells of the pancreas. Conditions were optimized to radiolabel gliclazide with radioiodine via electrophilic substitution reaction. Then, it was formulated as a nanoemulsion system using olive oil and egg lecithin by hot homogenization followed by ultrasonication. The system was assessed for its suitability for parenteral administration and drug release. Then, the tracer was evaluated in silico and in vivo in normal and diabetic rats. The labeled compound was obtained with a high radiochemical yield (99.3 ± 1.1%) and good stability (>48 h). The radiolabeled nanoemulsion showed an average droplet size of 24.7 nm, a polydispersity index of 0.21, a zeta potential of −45.3 mV, pH 7.4, an osmolality of 285.3 mOsm/kg, and viscosity of 1.24 mPa.s, indicating suitability for parenteral administration. In silico assessment suggested that the labeling did not affect the biological activity of gliclazide. The suggestion was further supported by the in vivo blocking study. Following intravenous administration of nanoemulsion, the pancreas uptake was highest in normal rats (19.57 ± 1.16 and 12 ± 0.13% ID) compared to diabetic rats (8.51 ± 0.16 and 5 ± 0.13% ID) at 1 and 4 h post-injection, respectively. All results supported the feasibility of radioiodinated gliclazide nanoemulsion as a tracer for pancreatic β-cells. [ABSTRACT FROM AUTHOR]

Real-world evidence (RWE) plays an important role in the management of type 2 diabetes (T2D). It provides data about the effectiveness and safety of an intervention from outside the randomised controlled trial (RCT) setting and allows healthcare professionals (HCPs) to determine if RCT data are applicable to their patients in routine clinical practice. This review provides a discussion of the value of RWE in T2D management in day-to-day clinical practice, with a focus on RWE with sulfonylureas (SUs), and presents two examples of a new generation of international real-world studies in people with T2D managed in routine clinical practice. RWE plays a valuable role in advising HCPs in the day-to-day management of T2D, informing regulatory authorities with regard to pharmacovigilance and post-approval updates, and providing insights with regard to patients' treatment adherence and preference. RWE should be used alongside RCTs to increase HCP awareness and understanding of their patients' perspectives, potentially allowing for improvements in treatment adherence, glycaemic control and health-related quality of life (HRQoL). In addition, real-world studies must be conducted in a way that generates robust RWE by limiting the risks of bias and confounding as much as possible. A growing body of RWE is emerging from Asia. For example, in a preliminary HRQoL analysis of the Joint Asia Diabetes Evaluation (JADE) Register, Asian people with T2D had better HRQoL with gliclazide-based treatment than with other SU agents, despite being older and having more diabetes-related complications. [ABSTRACT FROM AUTHOR]

A novel organic–inorganic gliclazide-loaded composite bead was developed by an ionic gelation process using acidified CaCl2, chitosan and tetraethylorthosilicate (TEOS) as a crosslinker. The beads were manufactured by crosslinking an inorganic silicone elastomer (-OH terminated polydimethylsiloxane, PDMS) with TEOS at different ratios before grafting onto an organic backbone (Na-alginate) using a 32 factorial experimental design. Gliclazide’s encapsulation efficiency (EE%) and drug release over 8 h (% DR 8 h) were set as dependent responses for the optimisation of a pharmaceutical formula (herein referred to as ‘G op’) by response surface methodology. EE % and %DR 8 h of G op were 93.48% ± 0.19 and 70.29% ± 0.18, respectively. G op exhibited a controlled release of gliclazide that follows the Korsmeyer–Peppas kinetic model (R2 = 0.95) with super case II transport and pH-dependent swelling behaviour. In vitro testing of G op showed 92.17% ± 1.18 cell viability upon testing on C2C12 myoblasts, indicating the compatibility of this novel biomaterial platform with skeletal muscle drug delivery.

Objectives: The main goal of this research was to develop better tablet formulations by utilizing solid dispersions (SDs) and coprocessing excipients composite to achieve a better release rate of poor water-soluble gliclazide. Methods: The solvent evaporation method made SDs of gliclazide with different carriers carplex 67, carplex 80, and carplex FPS 500 (weight ratio, 1:1). The drug release patterns of the SDs were all evaluated and optimized. The SDs were illustrated by using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray powder diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Tablet batches FGC-1 to 8 were made using gliclazide-carplex 67 solid dispersions (GC67-SDs) and the co-processed composite of excipients, namely starch-MCC-povidone (SMP) and lactose-MCC-povidone-sodium starch glycolate (LMPS), prepared with coprocessing technology. We evaluated these batches by conducting physicochemical tests and comparing them to the existing commercial brand. Results: In a water medium, the release of gliclazide from SDs peaked within the first 30 min, showing a roughly 5∼6-fold increase compared to plain gliclazide. This quick dissolution rate may be due to the amorphization of the drug, which improved the specific surface area, and increased wettability caused by the hydrophilic properties of carplex particles. This has been confirmed through SEM, DSC, FTIR, and PXRD analysis. All FGC formulations had satisfactory pre-compression factor results, while the post-compression parameters indicated good mechanical strength and homogeneity across the blend. All produced tablets met the weight variation, friability, and disintegration time limit set by the compendia. Through in vitro drug release testing, it was discovered that all FGC tablet batches had consistent and nearly identical release results compared to SDs of gliclazide. However, the FGC-5 to 8 batches containing LMPS composites were determined to be the most effective formulations. In the first 30 min in a water medium, the percentage of drug generated from the FGC-8 tablets involving GC67-SDs and co-processed composite LMPS-4 is approximately 3.5 times higher than the average release of currently marketed products (MPs). After storing the selected FGC tablet batches for three months at 40 °C and 75 % RH, there were no noticeable alterations in the amount of drug and drug release profiles across the batches. Conclusion: Based on these findings, it appears that using the carplex silica-based SDs approach, along with gliclazide and co-processing excipients composite, could result in significant benefits compared to the current commercial brands. This approach could be effectively utilized to create solid dosage forms for drugs that have low solubility in water.

Introduction: Mobile radiation, also known as non-ionizing radiation, has been shown to have an impact on the formulation of Gliclazide tablets. The study's objective was to examine the impact of mobile phone radiation on the physical and chemical characteristics of Gliclazide, an oral medication utilized to manage type 2 diabetes by boosting insulin production from the pancreas. Materials and Methods: The tablets were exposed to mobile radiation for different periods, and the effects were evaluated using various analytical techniques such as UV-spectrophotometer and Mass spectrophotometer. The study found that the physical and chemical properties of Gliclazide tablets were significantly affected by mobile phone radiation. The tablets exposed to mobile radiation for longer periods showed a change in stability. Results: Furthermore, mobile radiation caused changes in the properties of the tablets, leading to changes in effectiveness. The study also found that mobile radiation caused a decrease in the dissolution rate of Gliclazide tablets, which can affect the bioavailability of the medication. The conclusion of the study revealed that mobile phone radiation significantly impacted the physical and chemical properties of Gliclazide tablets, potentially altering the medication's bioavailability. Conclusion: Therefore, it is important to consider the potential impact of mobile radiation on the formulation of Gliclazide tablets and other similar medications. More research is needed to understand the full extent of the effects of mobile radiation on medication formulations and to develop methods to protect medications from the effects of mobile radiation. [ABSTRACT FROM AUTHOR]

Gliclazide was approved as a treatment for type 2 diabetes in an era before model‐based drug development, and consequently, the recommended doses were not optimised with modern methods. To investigate various dosing regimens of gliclazide, we used publicly available data to characterise the dose‐response relationship using pharmacometric models. A literature search identified 21 published gliclazide pharmacokinetic (PK) studies with full profiles. These were digitised, and a PK model was developed for immediate‐ (IR) and modified‐release (MR) formulations. Data from a gliclazide dose‐ranging study of postprandial glucose were used to characterise the concentration–response relationship using the integrated glucose–insulin model. Simulations from the full model showed that the maximum effect was 44% of the patients achieving HbA1c <7%, with 11% experiencing glucose <3 mmol/L and the most sensitive patients (i.e., 5% most extreme) experiencing 35 min of hypoglycaemia. Simulations revealed that the recommended IR dose (320 mg) was appropriate with no efficacy gain with increased dose. However, the recommended dose for the MR formulation may be increased to 270 mg, with more patients achieving HbA1c goals (i.e., HbA1c <7%) without a hypoglycaemic risk higher than the resulting risk from the recommended IR dose. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) and hypertension are leading risk factors for death and disability in the Middle East. Both conditions are highly prevalent, underdiagnosed and poorly controlled, highlighting an urgent need for a roadmap to overcome the barriers to optimal glycaemic and blood pressure management in this region. This review provides a summary of the Evidence in Diabetes and Hypertension Summit (EVIDENT) held in September 2022, which discussed current treatment guidelines, unmet clinical needs and strategies to improve treatment outcomes for patients with T2DM and hypertension in the Middle East. Current clinical guidelines recommend strict glycaemic and blood pressure targets, presenting several treatment options to achieve and maintain these targets and prevent complications. However, treatment targets are infrequently met in the Middle East, largely due to high clinical inertia among physicians and low medication adherence among patients. To address these challenges, clinical guidelines now provide individualised therapy recommendations based on drug profiles, patient preferences and management priorities. Efforts to improve the early detection of prediabetes, T2DM screening and intensive, early glucose control will minimise long-term complications. Physicians can use the T2DM Oral Agents Fact Checking programme to help navigate the wide range of treatment options and guide clinical decision-making. Sulfonylurea agents have been used successfully to manage T2DM; a newer agent, gliclazide MR (modified release formulation), has the advantages of a lower incidence of hypoglycaemia with no risk of cardiovascular events, weight neutrality and proven renal benefits. For patients with hypertension, single-pill combinations have been developed to improve efficacy and reduce treatment burden. In conjunction with pragmatic treatment algorithms and personalised therapies, greater investments in disease prevention, public awareness, training of healthcare providers, patient education, government policies and research are needed to improve the quality of care of patients with T2DM and/or hypertension in the Middle East. [ABSTRACT FROM AUTHOR]

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Asprosin is a new hormone secreted mainly from white adipose tissue. It may be associated with the pathogenesis of obesity, diabetes and some metabolic diseases. The changes in plasma asprosin levels of experimental diabetic rats and the relation of these changes with liver glucose metabolism and some diabetes parameters were investigated, and the effects of metformin, gliclazide or curcumin treatment on plasma asprosin levels were tried. The study was designed as an animal model in diabetic rats The albino rats were divided into five groups. To induce diabetes, a single dose of STZ was injected intraperitoneally. Diabetics rats were treated intragastrically with metformin (D+Metformin group), gliclazide (D+Giliclazide group) or 20 curcumin (D+Curcumin group) for eight weeks. Fasting blood glucose, insulin levels and other parameters were measured. Plasma asporsin levels of untreated diabetic rats increased significantly (P [Med-Science 2023; 12(1.000): 167-74]

This article discusses a case of drug-induced phototoxicity in a 36-year-old woman who was taking gliclazide, an oral hypoglycemic agent for type 2 diabetes. The woman experienced severe burning and redness on her face after sun exposure, despite applying sunscreen. She had no other known comorbidities or history of photosensitivity reactions. The diagnosis of drug-induced phototoxicity was made based on her clinical features, and the drug was discontinued. Treatment with topical and systemic corticosteroids resulted in the resolution of symptoms. The article emphasizes the importance of recognizing and managing drug-induced phototoxicity to prevent further harm to patients. [Extracted from the article]

In this particular study, the objective was to examine how varying doses of gliclazide (1 mg kg-1) and Allium sativum (104 mg kg-1) affect interaction in rats with diabetes induced by alloxan. The diabetes was induced by intraperitoneal injection of alloxan at a dosage of 100 mg kg-1 of body weight. The results revealed that the administration of gliclazide at 1 mg kg-1 of body weight and A. sativum at 104 mg kg-1 body weight exhibited noteworthy antihyperglycemic effects. The objective was to determine whether an interaction exists between these two substances in the context of diabetic conditions. In combination the A. sativum significantly enhanced the antihyperglycaemic activity of gliclazide from 2nd to 8th h except at 4th h. Hence, there is existence of pharmacodynamic interaction between A. sativum and gliclazide. [ABSTRACT FROM AUTHOR]