Oral Hypoglycemic Agents

Real-time electrochemical monitoring in bioprocesses is an improvement over existing systems because it is versatile and provides more information to the user than periodic measurements of cell density or metabolic activity. Real-time electrochemical monitoring provides the ability to monitor the physiological status of actively growing cells related to electron transfer activity and potential changes in the proton gradient of the cells. Voltammetric and amperometric techniques offer opportunities to monitor electron transfer reactions when electrogenic microbes are used in microbial fuel cells or bioelectrochemical synthesis. Impedance techniques provide the ability to monitor the physiological status of a wide range of microorganisms in conventional bioprocesses. Impedance techniques involve scanning a range of frequencies to define physiological activity in terms of equivalent electrical circuits, thereby enabling the use of computer modeling to evaluate specific growth parameters. Electrochemical monitoring of microbial activity has applications throughout the biotechnology industry for generating real-time data and offers the potential for automated process controls for specific bioprocesses.

Introduction: Cervical cancer, the third most common cancer worldwide, is primarily caused by human papillomavirus (HPV) infection. This study aimed to develop natural extracts from the seeds of Carica papaya L. using the hydrodistillation method to evaluate their anticancer effects against HeLa cells.

Methods: The phytochemical composition of Carica papaya seeds’ essential oil was identified using gas chromatography mass spectrometry, and their cytotoxicity on proliferation, apoptosis, cell cycle phases, migration, and colony formation of HeLa cancer cell lines was examined. Moreover, the effects of essential oil on the protein expression levels related to apoptosis, cell cycle regulation, and migration in the treated HeLa cells were examined.

Result and discussion: The essential oil’s phytochemical composition was analyzed using gas chromatography-mass spectrometry (GC-MS), revealing benzyl isothiocyanate as the dominant compound (99.49%). Results demonstrated that the essential oil had a high cytotoxic effect, with an IC50 value of 16.78 µg/mL in the MTT assay. Apoptosis analysis indicated a significant increase in early and late apoptotic HeLa cells (23.45%). Flow cytometry revealed a G2/M phase arrest, which impeded cell division. The oil also exhibited a stronger inhibition of cancer cell migration (38.7%) than methotrexate (45.9%). Additionally, the clonogenic assay revealed a drastic reduction in colony formation (0.004% surviving fraction, 0.25% plating efficiency). ELISA results showed a profound effect on apoptosis-related proteins, reducing BCL-2, MMP-2, and CDK1/cyclin B1 expression, supported by molecular docking studies comparing its efficacy to methotrexate (−5.52, −6.29, and −5.75 vs −5.49, −5.44, and 5.18 kcal mol−, respectively). The findings suggest that Carica papaya seed essential oil may serve as a potential anticancer treatment for cervical cancer; however, further in vivo studies are required for validation in animal models.

PPARγ is the functioning receptor for the thiazolidinedione (TZD) class of anti-diabetes drugs including rosiglitazone and pioglitazone 1 . These drugs are full classical agonists for this nuclear receptor, but recent data has shown that many PPARγ-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPARγ by Cdk5 2 . Here we describe novel synthetic compounds that have a unique mode of binding to PPARγ, completely lack classical Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Intrahepatic bile acid accumulation due to inhibition of the bile salt export pump (BSEP) has been proposed as a mechanism for drug-induced cholestasis. Many cholestatic drugs do not initiate hepatotoxicity in rats, although they inhibit rat Bsep and cause elevated serum bile acid concentration. In this study, we examined changes in the taurocholate (TC) transport in response to cholestatic drug treatments in human and rat sandwich-cultured hepatocytes. Our experimental setup allows studying the basolateral and canalicular efflux simultaneously, thus comparing drug-induced changes in the vectorial efflux of TC. We found that TC elimination highly differs in human and rat hepatocytes. In human hepatocytes, an equal fraction of TC uptake was eliminated by basolateral (34.8%) and canalicular (34.4%) transporters and remained in the cells (30.5%), while in the case of rats, the basolateral transport was dominant (71.7%) and intracellular TC accumulation was negligible (6.9%). The inhibition of BSEP/Bsep resulted in significantly higher intracellular TC conc in humans than in rats. The 15-fold difference in intracellular TC conc of control in human versus rat hepatocytes was increased 25-fold by troglitazone treatment. MK571 and indomethacin decreased the basolateral efflux and significantly increased the intracellular TC conc in rats. In rat hepatocytes, the highest intracellular TC conc was observed with cyclosporine A and glibenclamide, which inhibited TC elimination in both directions. Nevertheless, the basolateral transport remained dominant. We conclude that in rats, the higher rate of basolateral bile salt efflux represents an additional protective mechanism in cholestasis, which contributes to species differences in response to hepatotoxic drugs.

Syzigium cumini or Eugenia jambolana usually known as 'jamun', is extensively consumed in several regions of India for the management of different diseases. The present investigation was carried to assess the antihyperlipidaemic characteristics of ethanolic extract of Syzigium cumini seed and fruit in hypercholesterolemic rats. Ethanolic extracts were obtained through conventional solvent extraction to evaluate their efficiency for improving the blood lipid profile. High cholesterol diet containing 1.5% of cholesterol was fed to the normal rats to raise their lipid profile i.e. cholesterol, low density lipoprotein and triglycerides. Then diet containing 3% extract was fed to the rats. Serum analysis showed that cholesterol, low density lipoproteins( LDL) and triglycerides were reduced in hyperlipidaemic rats and maximum reduction was up to 9.32, 11.46 and 7.09%, respectively and increase in high density lipoproteins (HDL) was 2.62%, due to nutraceutical seed extract (Nutraceutical ) diet. The nutraceutical fruit extract (Nutraceutical ) diet resulted in SE FE less reduction in the respective traits as compared to nutraceutical diet. Our research exhibited that jamunhas SE good protective role against hypercholesterolemia.

Dipeptidyl peptidase-4 (DPP4) inhibitors are a widely prescribed class of oral antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM). By prolonging the action of incretin hormones, particularly glucagon-like peptide-1 (GLP-1), they enhance glucose-dependent insulin secretion and reduce glucagon levels, leading to improved glycemic control. Beyond glycemic management, DPP4 inhibitors demonstrate a favorable safety profile with low risk of hypoglycemia and minimal impact on body weight. This comprehensive review details their pharmacological mechanisms, individual drug characteristics, clinical applications, adverse effects, recent advances, case studies, and future research directions, providing an in-depth resource for clinicians and researchers.

Lithium transport along the nephron _______________________________________ 726 Effect of lithium on water transport _________________________________________ 728 Overview of experimental studies 728 Role of aquaporin-2 729 Renal histological findings ________________________________________________ 731 Clinical studies on lithium-induced polyuria __________________________________ 732 Treatment of lithium-induced polyuria 733 Other complications of lithium administration ________________________________ 734 Drug interactions _______________________________________________________ 739 Clinical conditions that affect lithium metabolism _____________________________ 740 Management of lithium intoxication ________________________________________ 742 References _____________________________________________________________ 743

The presented case is a 68-year-old female with Type 1 diabetes (T1D). She was admitted for an emergency case with acute distress in January 2018 and was diagnosed with T1D with a blood glucose (BG) level of 459 mg/dL, HbA1c of 13.7%, glutamic acid decarboxylase autoantibody (GADA) level >2000 U/mL (<5 U/mL), and C-reactive protein (CRP) level of 1.10 ng/mL. She received Multiple Daily Injections (MDI) of insulin for 3 months, and then her HbA1c decreased to 7.3%. After that, she has been on a super-low carbohydrate diet (LCD) and received only Lantus XR and ipragliflozin. Serum CRP showed 0.2 ng/mL, suggesting a prolonged honeymoon period for years through continuous LCD.

For type 2 diabetes (T2D), the recommended meal has shifted from calorie restriction (CR) to a low carbohydrate diet (LCD). LCD gained worldwide prevalence through the efforts of Atkins and Bernstein, and we further developed LCD both medically and socially through the Japan LCD Promotion Association (JLCDPA). The beneficial and convenient methods of LCD include petite, standard, and super LCD, which have carbohydrate ratios of 40%, 26%, and 12%, respectively. For these three types, the approximate permitted carbohydrate amounts in each meal appear to be 20g, 30g, and 40g. Some foods with lower carbohydrate content include eggs (0.1g), a piece of cheese (0.2g), chicken meat (180g) (0.4g), and Japanese tofu (300g) (4g).

The patient is a 55-year-old male with type 2 diabetes (T2D). In his 20s, 30s, and 50s, his body weight was 80 kg, 95 kg, and 90 kg, respectively. HbA1c was 10.9% in March 2023, and he was prescribed imeglimin (Twymeeg) as an oral hypoglycemic agent (OHA). HbA1c decreased to 9.3%, 7.2%, and 6.8% within just 3 months. His body weight also decreased from 86 kg to 82 kg during this period. Liver function tests showed improvement between March and May 2023, with AST decreasing from 54 to 24 U/L, ALT from 121 to 28 U/L, and GGT from 45 to 18 U/L, respectively. This suggests an improvement in fatty liver.

The antidiabetic activity of Momordica charantia (L.), Cucurbitaceae, a widely-used treatment for diabetes in a number of traditional medicine systems, was investigated in vitro. Antidiabetic activity has been reported for certain saponins isolated from M. charantia. In this study insulin secretion was measured in MIN6 β-cells incubated with an ethanol extract, saponin-rich fraction, and five purified saponins and cucurbitane triterpenoids from M. charantia, 3β,7β,25trihydroxycucurbita-5,23(E)-dien-19-al (1), momordicine I (2), momordicine II (3), 3hydroxycucurbita-5,24-dien-19-al-7,23-di-O-β-glucopyranoside (4), and kuguaglycoside G (5). Treatments were compared to incubation with high glucose (27 mM) and the insulin secretagogue, glipizide (50 μM). At 125 μg/ml, an LC-ToF-MS characterized saponin-rich fraction stimulated insulin secretion significantly more than the DMSO vehicle, p=0.02. At concentrations 10 and 25 μg/ml, compounds 3 and 5 also significantly stimulated insulin secretion as compared to the vehicle, p≤0.007, and p= 0.002, respectively. This is the first report of a saponin-rich fraction, and isolated compounds from M. charantia, stimulating insulin secretion in an in vitro, static incubation assay.

Next-generation sequencing (NGS) has revolutionized the field of genomics and created new opportunities for basic research. We described the strategy for the NGS validation of the "dysglycaemia panel" composed by 44 genes related to glucose metabolism disorders (MODY, Wolfram syndrome) and familial renal glycosuria using Ion AmpliSeq technology combined with Ion-PGM. Anonymized DNA of 32 previously genotyped cases with 33 different variants were used to optimize the methodology. Standard protocol was used to generate the primer design, library, template preparation, and sequencing. Ion Reporter tool was used for data analysis. In all the runs, the mean coverage was over 200×. Twenty-nine out of thirty three variants (96.5%) were detected; four frameshift variants were missed. All point mutations were detected with high sensitivity. We identified three further variants of unknown significance in addition to pathogenic mutations previously identified by Sanger sequencing. The NGS panel allowed us to identify pathogenic variants in multiple genes in a short time. This could help to identify several defects in children and young adults that have to receive the genetic diagnosis necessary for optimal treatment. In order not to lose any pathogenic variants, Sanger sequencing is included in our analytical protocol to avoid missing frameshift variants.

Dieci Società Scientifiche della Regione Lazio hanno convenuto di avviare un percorso di condivisione delle scelte diagnostiche e terapeutiche nella gestione delle dislipidemie, finalizzato a migliorare la qualità complessiva del trattamento di queste condizioni molto comuni nella popolazione e con un grande impatto sul rischio cardiovascolare. Tale percorso di condivisone è basato sulle evidenze scientifiche tenendo, comunque nel debito conto le risorse economiche disponibili. Il risultato è rappresentato da questo Documento di Consenso che ha lo scopo di fornire, attraverso la risposta ad alcuni semplici quesiti clinici, le indicazioni operative fondamentali per aiutare il medico a scegliere un percorso diagnostico-terapeutico “clinicamente sostenibile” e che sia effettivamente aperto alla soluzione dei problemi dei pazienti.

Various discussions have continued concerning low carbohydrate diet (LCD) and calorie restriction (CR). The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) have gradually recognized LCD as the recommendation for nutritional treatment. Recent reports have shown the predominance of LCD with clinical evidence from the accumulated data of the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS), with analyses of total LCD scores (TLCDS). Using TLCDS to analyze 139 thousand person-years, the hazard ratio (HR) of total mortality was 0.87 for TLCDS and 0.76 for vegetable (VLCDS). Authors continue developing LCD activities through the Japan LCD Promotion Association (JLCDPA).

The Garos form the largest tribal group of people of north-central Bangladesh residing mainly in Mymensingh, Netrakona, Gazipur, Sherpur and Tangail districts. Although a number of Garos have recently adopted Christianity, they basically follow their own religion with its associated customs and rituals. The Garos also have their own traditional healers known as khamal or kamal, who serve as their primary health-care providers. In the absence of their own alphabet and because of their settlement in a number of districts, traditional medicinal uses of plants differ between the khamals, who besides arranging festivals also treat patients and are considered experts on medicinal plants. It was the objective of the present study to conduct an ethnobotanical survey of the Garos residing in Netrakona district, Bangladesh because such information is lacking for the Garo community in this district. After obtaining informed consent from the healers, a semistructured questionnaire was used to interview the various healers practicing within the community. Ethnobotanical methods like guided field walks were undertaken, where the informants showed the medicinal plants used by them from areas where they usually collected them and at the same time mentioned their names and described their uses. Plant specimens were collected and dried on the field and later brought back and identified at the Bangladesh National Herbarium. The names and uses of 74 plant species distributed into 45 families were obtained in the present survey. The Fabaceae family provided the largest number of plant species (eight), followed by the Araceae, Asteraceae, Moraceae, Solanaceae, and Verbenaceae families (three plants each). Leaves formed the major plant part used (33.6%), followed by whole plant (15.9%) and fruits (15.0%). The various ailments treated by the plants included respiratory tract infections, gastrointestinal disorders, sprains and fractures, skin ailments, malaria, mental disorders, hepatic disorders, diabetes, influenza, urinary tract infections, hypertension, debility, measles, chicken pox, toothache, gynecological problems, sexual disorders, and helminthiasis. Some plants were also used as antidote to poison, diuretic, and abortifacient. Reported pharmacological studies validate the use of a number of medicinal plants by the khamals. Taken together, the medicinal plants used by the Garos form a rich source of indigenous knowledge and through proper scientific studies can form the basis for discovery of lead compounds, which can play a role for various therapeutic purposes.

Diabetes mellitus, especially type 2 diabetes mellitus, is a major global health concern. Many antidiabetic drugs are widely used, but they have limitations such as side effects and high cost. As a result herbal alternatives are being explored. Medicinal plants are being used in traditional medicine systems from ancient times. They offer promising therapeutic response due to their diverse phytochemical constituents and multi-targeted mechanism of action. This review summarizes evidences on selected herbal antidiabetic agents including Trigonella foenum-graecum (fenugreek), Momordica charantia (bitter gourd), Cinnamomum (cinnamon), Gymnema sylvestre (gurmar), Ocimum sanctum (tulsi), Allium sativum (garlic), and Aloevera. These plants have demonstrated beneficial effects by stimulating insulin secretion, enhancing insulin sensitivity, improving lipid profiles, and also providing antioxidant protection. Experimental and clinical studies support their role in lowering fasting blood glucose, and lipid levels, with some effects comparable to standard antidiabetic drugs such as glibenclamide. Despite the encouraging results, challenges remain such as standardization, large-scale clinical validation, and safety assurance. Future research including clinical trials and mechanistic studies can be essential for the translation of these herbal antidiabetics into modern evidence-based treatment for diabetes.

This research work accessed the effects of kolaviron (a methanolic extract of Garcinia kola seeds) on microanatomy of kidneys and biochemical parameters with a view to determining its relationship to renal functions treated with clomiphene citrate. A total of thirty adult female Wistar rats were used for this experiment. The animals were randomly divided into six (6) groups: A, B, C, D, E and F with five (5) animals in each group. Group A, were the control group that were given distilled water orally once daily for 14 days; Group B were given kolaviron orally at concentration of 200 mg/kg body weight once daily for 14 days; Group C were given kolaviron orally at concentration of 100 mg/kg twice daily for 14 days; Group D were given clomiphene citrate orally at concentration of 0.50 mg/kg body weight for 5 days; Group E were given kolaviron orally at concentration of 200 mg/kg body weight once daily for 14 days after which clomiphene citrate were administered at concentration of 0.50...

Biguanides can function as oral antihyperglycemic drugs. They were used for diabetes mellitus or prediabetes treatment over the last nine decades, but they lost their popularity in 1970s because of phenformin and regained with metformin. For metformin, the most common side effects are diarrhea and dyspepsia, occurring in up to 30% of patients. The most important and serious side effect is lactic acidosis. Phenformin was removed from the markets before 1970, because it caused lactic acidosis in 40-65 patients in 100,000 patient-years. Metformin causes lactate accumulation only in patients who have hepatic failure, renal failure or in patients who attempt suicide with high dosage of drugs. In this report, we present five patients who used high doses of metformin for suicide attempt.

Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin. After 30weeks, addition of exenatide BID or insulin lispro resulted in significant (P&lt;0.0001) reductions in HbA1c (exenatide BID: -0.9% [-10mmol/mol]; insulin lispro: -1.2% [-13mmol/mol]). Weight was stable in the exenatide BID group (-0.1kg) and increased significantly (+3.4kg; P&lt;0.0001) with insulin lispro. Major and minor hypoglycemia occurred less frequently (40 vs. 253 events) with exenatide BID compared w...

Neonatal effects of drugs administered to mothers before delivery depend on the quantity that crosses the placental barrier, which is determined by the pharmacokinetics of the drug in the mother, fetus, and placenta. Diabetes mellitus can alter the kinetic disposition and the metabolism of drugs. This study investigated the placental transfer of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in pregnant women with gestational diabetes mellitus (GDM) submitted to peridural anesthesia. A total of 10 normal pregnant women (group 1) and 6 pregnant women with GDM (group 2) were studied, all at term. The patients received 200 mg 2% lidocaine hydrochloride by the peridural locoregional route. Maternal blood samples were collected at the time of delivery and, after placental expulsion, blood samples were collected from the intervillous space, umbilical artery, and vein for determination of lidocaine and MEGX concentrations and analysis of the placental transfer of the drug. Th...

There is an urgent need to find consensus on screening, diagnosing and treating all degrees of DYSGLYCEMIA that may occur during pregnancies in Brazil, considering that many cases of DYSGLYCEMIA in pregnant women are currently not diagnosed, leading to maternal and fetal complications. For this reason the Brazilian Diabetes Society (SBD) and the Brazilian Federation of Gynecology and Obstetrics Societies (FEBRASGO), got together to introduce this proposal. We present here a joint consensus regarding the standardization of clinical management for pregnant women with any degree of Dysglycemia, on the basis of current information, to improve medical assistance and to avoid related complications of Dysglycemia in pregnancy to the mother and the fetus. This consensus aims to standardize the diagnosis among general practitioners, endocrinologists and obstetricians allowing the dissemination of information in basic health units, public and private services, that are responsible for screening, diagnosing and treating disglycemic pregnant patients.

Recently, actual changes in blood glucose can be measured by continuous glucose monitoring (CGM) using FreeStyle Libre. The case involves a 67-year-old male patient with type 2 diabetes (T2D) treated with Multiple Daily Insulin (MDI) therapy, who underwent CGM. Analysis of the CGM data revealed that hyperglycemia resulted from increased carbohydrate intake and irregular meal timings and quantities. The estimated HbA1c from CGM was 6.6%, whereas the HbA1c value recorded at the outpatient clinic during the same period was 7.3%. The use of CGM applications encourages diabetic patients to be mindful of their carbohydrate intake in daily life, leading to an increased ratio of time spent in the target range (TIR).

Objectives In this study, our main objective was to estimate the therapeutic effectiveness of the formulated solid dispersion of glibenclamide (GSD) with improved dissolution profiles in comparison with pure glibenclamide (GLB) by means of a fructose-fed diabetic rat model. Methods To evaluate the pharmacological effectiveness of the formulated GSD, a fructose-fed diabetic rat model evolved and the obtained consequences were compared with the conventional GLB treatment. Key findings GSD exhibited improved glucose and lipid-lowering efficacy of GSD in contrast to pure GLB after 15 days of treatment. Low dose (0.5 mg/kg) and high dose (5 mg/kg) of GSD showed significant lowering of blood glucose which is 6 ± 0.2 mmol/L and 5.6 ± 0.3 mmol/L respectively after 15 days of treatment is much better than that of pure GLB (6.2 ± 0.4 mmol/L). Furthermore, low dose of GSD presented approximately comparable beneficiary effects in regard to triglycerides (72.00 ± 7.23 mg/dL), total cholesterol (110.33 ± 5.78 mg/ dL), low-density lipoprotein (67.60 ± 5.21 mg/dL) and high-density lipoprotein (28.33 ± 1.53 mg/dL) as pure GLB after 15 days. Additionally, histological studies as well confirmed no fatty infiltration from the liver by GSD as compared with GLB which was consistent with the biochemical parameters. Conclusions For treating diabetes and hyperlipidaemia, the formulated GSD might be a potential substitute for traditional GLB.

Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown. Recent studies have shown that human OCT1 is highly polymorphic. We investigated whether OCT1 plays a role in the action of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug. In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis. In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished. Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were identified. Notably, OCT1-420del (allele frequency of about 20% in white Americans), previously shown to have normal activity for model substrates, had reduced activity for metformin. In clinical studies, the effects of metformin in glucose tolerance tests were significantly lower in individuals carrying reduced function polymorphisms of OCT1. Collectively, the data indicate that OCT1 is important for metformin therapeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug.

Semecarpus anacardium, commonly known as Bhilwa or the Marking Nut Tree, is a medicinally significant deciduous tree found throughout India and neighbouring regions. This review explores its ethnomedicinal legacy, botanical traits, phytochemistry, and multifaceted pharmacological activities. Bioactive constituents such as biflavonoids, bhilawanols, and phenolic compounds contribute to its documented anticancer, antioxidant, anti-inflammatory, antiatherogenic, and neuroprotective effects. The species demonstrates potent antimicrobial, antihyperglycemic, and antispermatogenic activities, supporting wide-ranging traditional and contemporary therapeutic applications. Despite promising preclinical evidence, challenges persist regarding standardization, clinical validation, and

Diabetes mellitus, especially type 2 diabetes mellitus, is a major global health concern. Many antidiabetic drugs are widely used, but they have limitations such as side effects and high cost. As a result herbal alternatives are being explored. Medicinal plants are being used in traditional medicine systems from ancient times. They offer promising therapeutic response due to their diverse phytochemical constituents and multi-targeted mechanism of action. This review summarizes evidences on selected herbal antidiabetic agents including Trigonella foenum-graecum (fenugreek), Momordica charantia (bitter gourd), Cinnamomum (cinnamon), Gymnema sylvestre (gurmar), Ocimum sanctum (tulsi), Allium sativum (garlic), and Aloevera. These plants have demonstrated beneficial effects by stimulating insulin secretion, enhancing insulin sensitivity, improving lipid profiles, and also providing antioxidant protection. Experimental and clinical studies support their role in lowering fasting blood glucose, and lipid levels, with some effects comparable to standard antidiabetic drugs such as glibenclamide. Despite the encouraging results, challenges remain such as standardization, large-scale clinical validation, and safety assurance. Future research including clinical trials and mechanistic studies can be essential for the translation of these herbal antidiabetics into modern evidence-based treatment for diabetes.

Itraconazole, a triazole antifungal agent, represents a cornerstone in the management of systemic and superficial fungal infections. Its clinical value is particularly evident in immunocompromised populations, where prophylactic use mitigates the risk of invasive and life-threatening mycoses. This review explores itraconazole in depth, highlighting its FDA-approved and off-label indications, mechanism of action, pharmacokinetics, and practical considerations in administration. Special attention is given to its adverse effect profile, most notably cardiotoxicity and hepatotoxicity, along with contraindications and potential drug-drug interactions inherent to its metabolism via CYP3A4. The importance of therapeutic drug monitoring and laboratory surveillance is emphasized to ensure efficacy while minimizing toxicity. Finally, the discussion underscores the necessity of interprofessional collaboration—encompassing physicians, pharmacists, nurses, infectious disease specialists, social workers, and mental health professionals—in optimizing patient outcomes. Through its broad-spectrum activity, itraconazole continues to be an indispensable antifungal therapy, albeit one requiring vigilant monitoring and coordinated care.

Background: Currently available short-acting insulin analogs have slower absorption compared with endogenous insulin occasionally resulting in immediate postprandial hyperglycemia. Intradermal (ID) injection facilitates faster drug absorption and may result in improved insulin pharmacokinetics. Methods: Seventeen patients with type 2 diabetes were included in this single-center, pilot, open-label crossover study. Patients received 0.2 U/kg Insulin aspart ID injections using a MicronJet (MJ) needle and subcutaneous (SC) injections, using a conventional needle in a crossover design. Thirteen patients were studied under fasting conditions and four before a standard meal test. The pharmacokinetic/pharmacodynamic (PK/PD) profile, as well as the safety and tolerability of injections, was compared. Results: Fourteen patients completed the study per-protocol. ID versus SC injection demonstrated significantly shorter Tmax (median 35 vs. 87.5 min [P < 0.001]), while the Cmax did not significantly differ (median 80 vs. 55 lU/mL [P = 0.085]). Median insulin area under the curve (AUC; 360 min) did not differ between the groups (9914 vs. 10,936 lU/mL/min [p = 0.077]), yet 0-60 min insulin AUC was higher with ID versus SC injection (mean -SD 3821 -1429 vs. 2534 -737 lU/mL/min [p = 0.01]) and 4-6 h AUC was lower with ID versus SC injection (mean -SD 2054 -858 vs. 2929 -1412 lU/mL/min [p = 0.02]). The relative bioavailability of the ID versus the SC insulin (AUC ID /AUC SC ) was similar (median 0.91 [95% confidence interval 0.73-1.27]). Conclusions: ID insulin injection delivered through an MJ needle demonstrated superior PK profile compared with conventional SC administration, including shorter Tmax and higher early and lower late exposure in patients with type 2 diabetes. This may help achieve better insulin coverage of meals and lower postprandial glucose excursions.

Introduction: Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the ( patho) physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of incretin-based therapies in type 2 diabetes. Methods and analyses: 60 patients with type 2 diabetes will undergo acute and prolonged randomised, double-blind, intervention studies. The acute intervention will consist of intravenous administration of the GLP-1 receptor agonist exenatide or placebo. For the prolonged intervention, patients will be randomised to 12-week treatment with the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebos. For each examined organ system, a primary end point is defined. Primary cardiovascular end point is change in resting heart rate variability assessed by beat-to-beat heart rate monitor and spectral analyses software. Primary renal end point is change in glomerular filtration rate assessed by the classic inulin clearance methodology. Primary gastrointestinal end points are change in pancreatic exocrine function assessed by MRI-techniques (acute intervention) and faecal elastase-1 levels (12-week intervention). Secondary end points include systemic haemodynamics, microvascular function, effective renal plasma flow, renal tubular function, pancreatic volume and gallbladder emptying-rate. The study is approved by the local Ethics Review Board (VU

To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology. For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg (n = 19), sitagliptin 100 mg (n = 19), or matching placebos (n = 17) once daily for 12 weeks. The primary end point was change in exocrine function (intraduodenal pancreatic fluid secretion, lipase activity, fecal elastase-1, and chymotrypsin). Secondary end points included changes in plasma enzyme concentrations and pancreatic morphology (per MRI). No patient developed pancreatitis. Sitagliptin increased intraduodenal pancreatic fluid secretion by 16.3 mL (95% CI -0.3-32.9; P = 0.05), whereas liraglutide did not change exocrine pancreatic function. Neither therapy increased lipa...

Incretin-based therapies, that is, glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors, are relatively novel antihyperglycaemic drugs that are frequently used in type 2 diabetes management. Apart from glucose-lowering, these agents exhibit pleiotropic actions that may have favourable and unfavourable clinical consequences. Incretin-based therapies have been associated with heart rate acceleration, heart failure, acute renal failure and acute pancreatitis. Conversely, these agents may reduce blood pressure, glomerular hyperfiltration, albuminuria and hepatic steatosis. While large-sized cardiovascular safety trials can potentially identify the clinical significance of some of these pleiotropic actions, small-sized mechanistic studies are important to understand the (patho)physiological rationale of these findings. The current protocol describes a mechanistic study to assess cardiovascular, renal and gastrointestinal effects, and mechanisms of i...

Aims/Introduction: The influence of overweight/obesity on the clinical efficacy and safety of sodium-glucose co-transporter 2 inhibitors is unclear. We carried out a pooled analysis to examine the impact of body mass index on the efficacy and safety of ipragliflozin. Materials and Methods: Patient-level data were pooled for five Japanese double-blind trials (NCT00621868, NCT01057628, NCT01135433, NCT01225081 and NCT01242215) in which patients were randomized to ipragliflozin or a placebo as monotherapy, or in combination with metformin, pioglitazone or a sulfonylurea. Outcomes included the changes in hemoglobin A1c, fasting plasma glucose, bodyweight and treatment-emergent adverse events. Patients were divided into four body mass index categories. Results: Hemoglobin A1c, fasting plasma glucose and bodyweight decreased significantly in the ipragliflozin group compared with the placebo group in all body mass index categories, and in the total cohort (all P < 0.001). Hemoglobin A1c did not improve in 11.2 and 69.2% of patients in the ipragliflozin and placebo groups, respectively. The change in hemoglobin A1c was weakly correlated with the change in bodyweight in all patients (r = 0.136, P = 0.002). Regarding laboratory variables, the placebo-subtracted difference tended to be greater in patients with higher body mass index for aspartate aminotransferase, alanine aminotransferase, c-glutamyl transpeptidase and uric acid. The incidences of treatment-emergent adverse events were similar between the ipragliflozin and placebo groups in all patients combined and in the four body mass index categories. Conclusions: These results show that the efficacy and safety of ipragliflozin are not influenced by obesity/overweight in Japanese patients.

Hepatocellular accumulation of bile acids due to inhibition of the canalicular bile salt export pump (BSEP/ABCB11) is one proposed mechanism of drug-induced liver injury (DILI). Some hepatotoxic compounds also are potent inhibitors of bile acid uptake by Na + -dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1). This study used a cassette dosing approach in rat and human sandwich-cultured hepatocytes (SCH) to determine whether known or suspected hepatotoxic drugs inhibit bile acid transport individually or in combination. [ 3 H]-Taurocholate served as the NTCP/BSEP probe substrate. Individually, cyclosporin A and rifampin decreased taurocholate in vitro biliary clearance (Cl biliary ) and biliary excretion index (BEI) by more than 20% in rat SCH, suggesting that these drugs primarily inhibited canalicular efflux. In contrast, ampicillin, carbenicillin, cloxacillin, nafcillin, oxacillin, carbamazepine, pioglitazone, and troglitazone decreased the in vitro Cl biliary by more than 20% with no notable change in BEI, suggesting that these drugs primarily inhibited taurocholate uptake. Cassette dosing (n=2-4 compounds per cassette) in rat SCH yielded similar findings, and results in human SCH were consistent with rat SCH. In summary, cassette dosing in SCH is a useful in vitro approach to identify compounds that inhibit the hepatic uptake and/or excretion of bile acids, which may cause DILI.

Hepatocellular accumulation of bile acids due to inhibition of the canalicular bile salt export pump (BSEP/ABCB11) is one proposed mechanism of drug-induced liver injury (DILI). Some hepatotoxic compounds also are potent inhibitors of bile acid uptake by Na + -dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1). This study used a cassette dosing approach in rat and human sandwich-cultured hepatocytes (SCH) to determine whether known or suspected hepatotoxic drugs inhibit bile acid transport individually or in combination. [ 3 H]-Taurocholate served as the NTCP/BSEP probe substrate. Individually, cyclosporin A and rifampin decreased taurocholate in vitro biliary clearance (Cl biliary ) and biliary excretion index (BEI) by more than 20% in rat SCH, suggesting that these drugs primarily inhibited canalicular efflux. In contrast, ampicillin, carbenicillin, cloxacillin, nafcillin, oxacillin, carbamazepine, pioglitazone, and troglitazone decreased the in vitro Cl biliary by more than 20% with no notable change in BEI, suggesting that these drugs primarily inhibited taurocholate uptake. Cassette dosing (n=2-4 compounds per cassette) in rat SCH yielded similar findings, and results in human SCH were consistent with rat SCH. In summary, cassette dosing in SCH is a useful in vitro approach to identify compounds that inhibit the hepatic uptake and/or excretion of bile acids, which may cause DILI.

Aims/hypothesis Metformin is believed to reduce glucose levels primarily by inhibiting hepatic glucose production. Recent data indicate that metformin antagonises glucagondependent glucose output, suggesting that compensatory mechanisms protect against hypoglycaemia. Here, we examined the effect of metformin on glucose metabolism in humans after a glycogen-depleting fast and the role of reducedfunction alleles in OCT1 (also known as SLC22A1). Methods In a randomised, crossover trial, healthy individuals with or without reduced-function alleles in OCT1 were fasted for 42 h twice, either with or without prior treatment with 1 g metformin twice daily. Participants were recruited from the Pharmacogenomics Biobank of the University of Southern Denmark. Treatment allocation was generated by the Good

Osteoporóza je definovaná úbytkom kostnej hmoty, poruchami architektúry kostí a tendenciou k zlomeninám. Osteoporózou trpí 7 až 8% populácie a je to epidemická civilizačná choroba. Dôležitá je presná diagnostika a účinná liečba, aby sa predišlo zlomeninám. Osteoporóza je spoločensky závažne ochorenie pohybového aparátu a v súvislosti s výrazným nárastom a vysokými nákladmi na diagnostiku a liečbu je významným celosvetovým medicínskym a spoločenským problémom. Pri osteoporóze sa objavujú bolesti chrbta, zníženie výšky, problémy s pohybom, ťažkosti pri chôdzi, stúpaní po schodoch, ale i pri dlhšom státí či sedení. Najzávažnejším zdravotným dôsledkom osteoporózy sú zlomeniny.

Introduce: Perioperative myocardial infarction after surgical coronary artery revascularization is an important diagnostic and therapeutic issue. Urgent coronary and bypass angiography is a relatively new strategy, but there are few publications on this subject. Aim: The aim of this study is to present the results of urgent diagnostic angiography and percutaneous interventions in patients with symptoms of acute myocardial ischaemia during the first 24 hours after coronary artery bypass graft surgery. Material and Methods: The study group comprised 153 (1.38%) among 11 090 patients who underwent coronary artery surgery. They underwent early coronary and bypass angiography due to the symptoms of acute myocardial ischaemia. Results: On the basis of angiography percutaneous intervention was performed in 62 (40.5%) pts, including balloon angioplasty of native artery or bypass in 23 (37.1%) pts and 39 (62.9%) pts had angioplasty with stent implantation. In 30 (19.6%) cases angiography revealed no new lesions in native arteries or grafts. 42 (27.4%) pts were qualified for conservative therapy, because of lack of technical possibilities for PCI or reoperation. Surgical reintervention was needed in only 25 (16.3%) pts. Conclusions: The diagnostic and therapeutic strategy of urgent angiography of coronary arteries and grafts in the event of perioperative ischaemia after coronary artery surgery (in the first 24 hours after operation) allows the precise diagnosis and establishment of optimal management. In more than 40% of pts percutaneous intervention is possible with a high success rate (above 85%). 80% of patients with acute perioperative ischaemia can avoid reoperation and those referred for repeat cardiac surgery had established indications and the range of reintervention.

The regulation of hepatic mitochondrial carnitine palmitoyl- transferase-I (CPT-I) was studied in rats during starvation and insulin-dependent diabetes and in rat H4IIE cells. The Vmax for CPT-I in hepatic mitochondrial outer membranes isolated from starved and diabetic rats increased 2-and 3-fold respectively over fed control values with no change in Km values for substrates. Regulation of malonyl-CoA sensitivity of CPT-I in isolated mitochondrial outer membranes was indicated by an 8-fold increase in K1 during starvation and by a 50-fold increase in K1 in the diabetic state. Peroxisomal and microsomal CPT also had decreased sensitivity to inhibition by malonyl-CoA during star-

Type 2 diabetes (T2D) is a crucial disease, and glucagon-like peptide 1 receptor agonists (GLP-1RA) have become prevalent as effective oral hypoglycemic agents (OHA). GLP-1RA has clinical effects such as improving glucose variability, reducing weight, and decreasing the risk of cardiovascular disease (CVD). However, recent problems include discontinuation, dropout, and incomplete adherence to GLP-1RA. The discontinuation rates of GLP-1RA were 26.2%, 30.8%, and 36.5% at 3, 6, and 12 months, respectively, and increased to 50.3% for obese patients without T2D. Discontinuation was significantly higher for patients with heart failure (odds ratio 1.09) and CVD (1.08), but not for those with CKD (1.03).

To compare the duration and effects of aqueous methanol Acacia-nilotica leaves extract and glibenclamide as hypoglycaemic and hypolipidaemic activity in diabetic rats. The experimental study was conducted at Shifa International Hospital in collaboration with National Institute of Health, Islamabad, from September 2010 to August 2011.Male Sprague Dawley albino rats were taken and divided into 8 equal groups. Groups I and II were the normal and diabetic control rats. Diabetes mellitus was induced in group II to VIII by administering 110 mg/kg body weight alloxanand at day 4, fasting blood glucose level of &gt;200 mg/dl confirmed diabetes. Acacia-nilotica leaves extract was given to group III, IV and V and glibenclamide to group VI to VIII for a period of 1-3 weeks. Blood samples were analysed for lipid profile using enzymatic calorimetric method and serum insulin by enzyme-linked immunosorbent assay on days 0, 7, 14, and 21. There were 64 rats in the study, with 8(12.5%) in each group...

Liraglutide, a long-lasting glucagon-like peptide-1 analogue, has been used for the treatment of patients with type 2 diabetes mellitus since 2009. In this study, we investigated the anti-diabetic effects and mechanisms of action of liraglutide in a spontaneous diabetic animal model, using KK/Upj-Ay/J (KKAy) mice. The KKAy mice were divided into 2 groups, the liraglutide group (mice were treated with 250 µg/kg/day liraglutide) and the model group (treated with an equivalent amount of normal saline). C57BL/6J mice were used as the controls (treated with an equivalent amount of normal saline). The treatment period lasted 6 weeks. During this treatment period, fasting blood glucose (FBG) levels and the body weight of the mice were measured on a weekly basis. Our results revealed that liraglutide significantly decreased FBG levels, the area under the curve following a oral glucose tolerance test and insulin tolerance test, increased serum insulin levels, reduced homeostasis model assessment of insulin resistance and increased the insulin sensitivity index. Furthermore, liraglutide ameliorated glycometabolism dysfunction by increasing glycolysis via hexokinase and glycogenesis via pyruvate kinase activation. An ultrastructural examination of the pancreas revealed that liraglutide improved the damaged state of islet β cells and increased the number of insulin secretory granules. The real-time PCR results revealed that the gene expression of glucose transporter 4 (GLUT4) increased following treatment with liraglutide. Liraglutide also upregulated the protein expression of GLUT4 in liver tissue and skeletal muscle. Our results suggest that liraglutide ameliorates glycometabolism and insulin resistance in diabetic KKAy mice by stimulating insulin secretion, increasing glycogenesis and glycolysis and upregulating the expression of GLUT4.

OBJECTIVE To evaluate weekly subcutaneous albiglutide versus daily sitagliptin in renally impaired patients with type 2 diabetes and inadequately controlled glycemia on a regimen of diet and exercise and/or oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS In this phase III, randomized, double-blind, multicenter, 52-week study, the primary study end point was HbA1c change from baseline at week 26 in patients with renal impairment, as assessed with estimated glomerular filtration rate and categorized as mild, moderate, or severe (≥60 to ≤89, ≥30 to ≤59, and ≥15 to ≤29 mL/min/1.73 m2, respectively). Secondary end points included fasting plasma glucose (FPG), weight, achievement of treatment targets, hyperglycemic rescue, and safety. RESULTS Baseline demographics were similar across treatment and renal impairment groups with overall mean age of 63.3 years, BMI of 30.4 kg/m2, HbA1c of 8.2% (66 mmol/mol), and diabetes disease duration of 11.2 years. HbA1c change from baseli...

GLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs. thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine. Patients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of &lt;5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26. At week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatmen...

To compare the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo. Patients with type 2 diabetes receiving metformin were randomized to albiglutide (30 mg), sitagliptin (100 mg), glimepiride (2 mg), or placebo. Blinded dose titration for albiglutide (to 50 mg) and glimepiride (to 4 mg) was based on predefined hyperglycemia criteria. The primary end point was change in HbA1c from baseline at week 104. Secondary end points included fasting plasma glucose (FPG), weight, and time to hyperglycemic rescue. Baseline characteristics were similar among the albiglutide (n = 302), glimepiride (n = 307), sitagliptin (n = 302), and placebo (n = 101) groups. Baseline HbA1c was 8.1% (65.0 mmol/mol); mean age was 54.5 years. The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg, respectively. At week 104, albiglutide significantly reduced HbA1c compared with placebo (-0.9% [-9.8 mmol/mol]; P &lt; 0.0001), sitagliptin (-0.4% [-4...

OBJECTIVE To evaluate the efficacy, safety, and tolerability of incremental doses of albiglutide, a long-acting glucagon-like peptide-1 receptor agonist, administered with three dosing schedules in patients with type 2 diabetes inadequately controlled with diet and exercise or metformin monotherapy. RESEARCH DESIGN AND METHODS In this randomized multicenter double-blind parallel-group study, 356 type 2 diabetic subjects with similar mean baseline characteristics (age 54 years, diabetes duration 4.9 years, BMI 32.1 kg/m2, A1C 8.0%) received subcutaneous placebo or albiglutide (weekly [4, 15, or 30 mg], biweekly [15, 30, or 50 mg], or monthly [50 or 100 mg]) or exenatide twice daily as an open-label active reference (per labeling in metformin subjects only) over 16 weeks followed by an 11-week washout period. The main outcome measure was change from baseline A1C of albiglutide groups versus placebo at week 16. RESULTS Dose-dependent reductions in A1C were observed within all albigluti...

Background: Mobile phone technologies including SMS (short message service) have been used to improve the delivery of health services in many countries. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. The aim of this study therefore is to measure the impact of a mobile phone SMS service on treatment success of newly diagnosed type 2 diabetes in an urban area of Bangladesh. Methods/design: This is a single-centred randomized controlled intervention trial (prospective) comparing standard-of-care with standard-of-care plus a mobile phone-based SMS intervention for 6 months. A total of 216 participants with newly diagnosed type 2 diabetes will be recruited. Data will be collected at the outpatient department of Bangladesh Institute of Health Science (BIHS) hospital at baseline and after 6 months. The primary outcome measure will be change in HbA1c between baseline and 6 months. The secondary outcome measures are self-reported medication adherence, clinic attendance, self-reported adoption of healthy behaviours, diabetes knowledge, quality of life and cost effectiveness of the SMS intervention. The inclusion criteria will be as follows: diagnosed as patients with type 2 diabetes by the BIHS physician, using oral medication therapy, living in Dhaka city, registered with the BIHS hospital, using a mobile phone, willing to return for follow up after 6 months and providing written informed consent. Participants will be allocated to control and intervention arms after recruitment using a randomization software. Data will be collected on socio-demographic and economic information, mobile phone use and habits, knowledge of prevention, management and complications of diabetes, self-perceived quality of life assessment, self-reported diseases, medical history, family history of diseases, medication history, medication adherence, health seeking behaviour, tobacco use, physical activity, diet, mental health status, life events and disability, anthropometric measurements of weight, height, blood pressure and blood tests for HbA1c. Discussion: Mobile phone SMS services have the potential to communicate with diabetes patients and to build awareness about the disease, improve self-management and avoid complications also in resource-limited setting. If this intervention proves to be efficient and cost-effective in the current trial, large-scale implementation could be undertaken. Trial registration: DRKS00005188.