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Background. The safety and efficacy of combination tablets of metformin plus sulfonylurea or plus dipeptidyl peptidase-4 inhibitors have not been studied previously. This study aimed to compare the efficacy and safety of Gliconorm versus Sitavia plus among patients with type 2 diabetes mellitus who fast Ramadan. Methods. This was an open-label study conducted from 1 May 2018 till 1 July 2018. People with type 2 diabetes mellitus who were drug-naive or on metformin only, with HbA1c < 10 % were included. The participants were divided into two groups. The first group was given Gliconorm (glibenclamide 5 mg + metformin 1000 mg), while the second group was given Sitavia plus (sitagliptin 50 mg + metformin 1000 mg) imme-diately after Iftar. Glycated hemoglobin (HbA1c) was measured before and after Ramadan. Several home recordings of blood glucose were collected. In addition, patients were asked to report any hypoglycemic or severe hyperglycemic episodes. Results. A total of 34 participants (18 women) (19 in the first group and 15 in the second group) were involved the study. The mean age was 49.6 ± 9.3 years. HbA1c reduced from 8.7 % (72 mmol/mol) to 7.6 % (60 mmol/mol) and from 8.7% (72 mmol/mol) to 7.7 % (61 mmol/mol) in the first and second group, respectively (p < 0.0001). Only one patient in the first group experienced one episode of hypoglycemia and hyperglycemia. Conclusion. Both medications seem to be safe and effective during Ramadan fasting.

The aim of the present work was to evaluate the selectivity of nicosulfuron, alone and in combinations, applied in post-emergence (V4) of glyphosate and sulfonylurea tolerant (RR/STS) soybean. The experiments were conducted in 2015/16 and 2016/17, in Piracicaba – state of São Paulo (SP). In 2016/17, the experiment was also conducted in Palotina – state of Paraná (PR). The experiment was a randomized block design, with four repetitions and 16 treatments, with combinations of nicosulfuron, glyphosate, chlorimuron, sulfometuron and cloransulam, applied alone or in tank mixture. Crop injury and variables related to agronomic performance were evaluated. Data were subjected to analysis of variance and treatment means were compared by the Tukey test. The results obtained are significant in the positioning of herbicides in RR/STS soybean, since in the five experiments, all the treatments were selective, except for glyphosate + sulfometuron which reduced the yield of a cultivar (CD 2630 RR/STS) in the 2015/16 season.

Received: August 1st, 2022 ; Accepted: December 10th, 2022 ; Published: February 2nd, 2023 ; Correspondence:larina.galina2014@gmail.com, poddimkina@gmail.com The migration of residual amounts of sulfonylurea and imidazolinone herbicides under conditions of washing water regime (sum of precipitation in forest and forest-steppe natural zone within 400–600 mm) in practice of intensive agricultural production has been studied. Vertical moisture transport in the soil determines the number of large pores, voids and cracks, and herbicide mobility depends on solubility of the active substance in water and adsorption equilibrium between the soil solution and the soil solid phase. The herbicide was applied to the soil surface, as is the case in practice. Then, pure water (without herbicide) was fed into the column from above, and the movement of water along the soil profile, as well as the adsorption of the herbicide by the soil and the desorption of the active substance by water, were simulated. The water supply to the column was stopped when the portions of water collected after filtering the water through the column contained less than the detection limit of herbicide residues chromatographically. The percentage content of sulfonylurea and imidazolinone herbicides residues in the soil solution varied depending on the nature of the active substance (maximum determined for imazapyr and lowest - metsulfuron-methyl) and soil type (more in acidic soil, compared to neutral and slightly alkaline soil). Effective management of pollution risks of the components of the natural environment (soil, surface and groundwater) provides a set of agrotechnological measures to reduce the number of large pores, voids and cracks in the arable layer.

Glipizide and glibenclamide remain some of the widely prescribed antidiabetic sulfonylurea drugs for the treatment of type 2 diabetes mellitus. Herein the authors report on an isocyanate-free synthetic procedure towards the preparation of these on demand drugs at multigram scale using continuous flow technology. The safety concern over the use of isocyanates in most of the existing synthetic routes was dealt with in this present work by using N-carbamates synthesised in situ from activation of amines with chloroformates as safer alternatives. An overall yield of 80-85 % was obtained for the semi-telescoped steps within 10 min total residence time.

A multigram-scale robust, efficient, and safe end-to-end continuous-flow process for the diabetes sulfonylurea drugs gliclazide, chlorpropamide, and tolbutamide is reported. The drugs were prepared by the treatment of an amine with a haloformate affording carbamate, which was subsequently treated with a sulfonamide to afford sulfonylurea. Gliclazide was obtained in 87% yield within 2.5 minutes total residence time with 26 g/h throughput; 0.2 kg of the drug was produced in 8 hours of running the system continuously. Chlorpropamide and tolbutamide were both obtained in 94% yield within 1 minute residence time with 184–188 g/h throughput; 1.4–1.5 kg of the drugs was produced in 8 hours of running the system continuously. N-Substituted carbamates were used as safe alternatives to the hazardous isocyanates in constructing the sulfonyl urea moiety.

OBJECTIVE Sulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However, there exists significant variability in glycemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA1c reduction. RESEARCH DESIGN AND METHODS As an initiative of the Metformin Genetics Plus Consortium (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortium, 5,485 White Europeans with type 2 diabetes treated with sulfonylureas were recruited from six referral centers in Europe and North America. We first estimated heritability using the generalized restricted maximum likelihood approach and then undertook genome-wide association studies of glycemic response to sulfonylureas measured as HbA1c reduction after 12 months of therapy followed by meta-analysis. These results were supported by acute glipizide challenge in humans who were naïve to type 2 diabetes medications, cis expression quantitative trait loci (eQTL), and functional validation in cellular models. Finally, we examined for possible drug-drug-gene interactions. RESULTS After establishing that sulfonylurea response is heritable (mean ± SEM 37 ± 11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA1c reduction at a genome-wide scale (P < 5 × 10−8). The C allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), P = 2.39 × 10−8), lower reduction in HbA1c. Similarly, the C allele was associated with higher glucose trough levels (β = 1.61, P = 0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). In 3,029 human whole blood samples, the C allele is a cis eQTL for increased expression of GXYLT1 (β = 0.21, P = 2.04 × 10−58). The C allele of rs10770791, in an intronic region of SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater reduction in HbA1c (P = 4.80 × 10−8). In 1,183 human liver samples, the C allele at rs10770791 is a cis eQTL for reduced SLCO1B1 expression (P = 1.61 × 10−7), which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use and SLCO1B1 genotype was observed (P = 0.001). In statin nonusers, C allele homozygotes at rs10770791 had a large absolute reduction in HbA1c (0.48 ± 0.12% [5.2 ± 1.26 mmol/mol]), equivalent to that associated with initiation of a dipeptidyl peptidase 4 inhibitor. CONCLUSIONS We have identified clinically important genetic effects at genome-wide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important in prescribing glucose-lowering drugs.

A large-scale study under controlled conditions was conducted to estimate the influence of diversified level of biotic: Fusarium culmorum and abiotic factors: herbicide (H; sulfosulfuron), fungicides (F1; cyproconazole + propiconazole), (F2; spiroxamine + tebuconazole + triadimenol) and humic biostimulator (B) on the profile of biochemical compounds (6 groups) and mycotoxins (11) in wheat grain. The following experiments were conducted: I: wheat inoculation with F. culmorum spore suspension (OD600 = 0.3; 0.7; 1.3), II: H, III: H+½F1+½F2, IV: H + F1 + F2, V: H + B, VI: H + F1 + F2 + B and VII: B. Multifactorial wheat response to biotic/abiotic stress factors was noted, manifesting in the highest reduction of total soluble carbohydrates (28%; IV) and proteins (34%, VII) related to abiotic factors. The lowest starch concentration was determined in Exp. I (600.54 µg g−1 dm), while the highest was found in control (794 µg g−1 dm). Furthermore, the maximum level of amino acids was observed in Exp II, and of phenolic compounds in Exp. I (894.59 and 933.93 µg g−1 dm, respectively). For the first time, acid phosphatase activity was determined in wheat grain under sulfonylurea, morpholine, triazole and humic biostimulator protection, indicating biostimulator contribution to elevated absorption of assimilable phosphorous forms and improvement of crop nutrition. Total mycotoxins: 3-AcDON, 15-AcDON, DON, NIV were the highest in inoculated wheat (Exp. I, 2063.9 µg kg−1). The most effective protection and the lowest concentration of mycotoxins was achieved in Exp. VI (155.3 µg kg−1, 67% reduction compared to control). Our study indicated that chemical treatments enriched by humic biostimulator could be implemented in the integrated program of wheat protection in agricultural practice.

Background: Hypoglycemia occurs when the blood sugar level is

Pesticide residues have seriously damaged the natural environment and social security. Here, we prepared the efficient functional biochar (FB) for sulfonylurea herbicides from cotton straw cellulose (CSC) by hydrothermal carbonization with the methacrylic acid. The molecular simulation of FB indicated that π-π electron-donor–acceptor (EDA) interaction and formation of charge-assisted H-bond were both the main factors for effective adsorption process. The adsorption process can match the pseudo-second-order kinetic equation and Freundlich model. The whole process is physical adsorption, spontaneous and rapid, and can quickly reach equilibrium. The FB with carbon–oxygen functional groups and aromatic conjugated structures can remove pesticides in water very quickly (within 30 s), with effective adsorption over 95% of Sulfonylurea herbicides (SUHs). Therefore, functional FB might be an effective way to get excellent absorbent for pesticide treatment.

У лекції розглянуті фармакологічні й клінічні аспекти використання глімепіриду, препарату сульфонілсечовини ІІІ покоління, у сучасній терапії цукрового діабету 2-го типу. Препарат має доведену ефективність і безпеку, є економічно доступним, характеризується низкою сприятливих позапанкреатичних ефектів, у тому числі кардіопротективними властивостями, що дозволяє з упевненістю рекомендувати його для лікування цукрового діабету 2-го типу.

Objective The study aimed to assess the long-term persistent symptoms of patients with diabetes mellitus (DM) and COVID-19 infection at 9 months after acute infection. Methods This single-center cross-sectional study was conducted from May 20 to June 1, 2021. Results A total of 112 patients were included in the present study. The most frequently reported persistent symptoms among DM group were fatigue (p = 0.01), shortness of breath (p = 0.01), and chest pain (p = 0.02) compared to non-DM group. Sulfonylurea use was associated with persistent cough (p = 0.04). Conclusion Long-term persistent symptoms of COVID-19 infection are common among patients with DM.

The evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary targets. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance in Monochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity and ALS gene sequences, followed by functional characterisation and ALS gene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively in MvALS1 or MvALS3. All MvALS4 alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression of MvALS1 and MvALS3 was prominently higher among all ALS genes. The higher expression of MvALS1 and MvALS3 is the driving force of the biased representation of genes during the evolution of herbicide resistance in M. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with ortho-alkoxy substitutions at the phenyl ring and evaluated their herbicidal activities. Some target compounds showed excellent herbicidal activity against monocotyledon weed species. When applied at 7.5 g ha-1, 6-11 exhibited more potent herbicidal activity against barnyard grass (Echinochloa crus-galli) and crab grass (Digitaria sanguinalis) than commercial acetohydroxyacid synthase (AHAS; EC 2.2.1.6) inhibitors triasulfuron, penoxsulam, and nicosulfuron at both pre-emergence and postemergence conditions. 6-11 was safe for peanut for postemergence application at this ultralow dosage, suggesting that it could be considered a potential herbicide candidate for peanut fields. Although 6-11 and triasulfuron share similar chemical structures and have close Ki values for plant AHAS, a significant difference has been observed between their LUMO maps from DFT calculations, which might be a possible factor that leads to their different behaviors toward monocotyledon weed species.

Medications used to treat diabetes mellitus are heterogeneous, with widely differing safety profiles in therapeutic use and in overdose. Insulin overdose may produce severe and prolonged hypoglycemia. Sulfonylurea poisoning should be treated with octreotide, sparing intravenous dextrose where possible. Acute metformin overdose may lead to life-threatening acidosis with elevated lactate concentrations, which may require hemodialysis. Glucagon-like peptide 1 agonists and dipeptidyl peptidase 4 inhibitors are benign in overdose in diabetic patients but may produce profound hypoglycemia in nondiabetic patients. Euglycemic diabetic ketoacidosis may develop in critically ill patients taking sodium-glucose co-transporter 2 inhibitors.

Increased drug related problems in diabetic patients treated with combinations of high doses of sulfonylureas and metformin was recently reported. This review article is aimed towards the assessment of drug related problems in patients treated with low-doses of sulfonylureas and biguanides. Sulphonylureas the second most commonly used antidiabetic drugs after metformin; there have been concerns regarding the cardiovascular safety of sulfonylureas. These safety concerns initiated with the University Group Diabetes Program conducted in the 1960s, found a sulfonylurea, tolbutamide, where tolbutamide is a first-generation sulfonylurea and was associated with an increased risk of all-cause and cardiovascular problems compared with placebo. Indeed, sulfonylureas have been associated with known cardiovascular risk factors like weight gain, fluid retention, and hypoglycemia. Phenformin, a biguanide, was related to lactic acidosis and withdrawn from use after causing increased risk factors within the University Group Diabetes Program since then, a more modern biguanide, metformin, has risen to its current place because the leading oral therapy for diabetes supported its relative lack of hazard from lactic acidosis and evidence especially from a subgroup of participants in the UK Prospective Diabetes Study, that it can reduce cardiovascular risk and other drug related problems. But there are certain studies showing that combination treatment with metformin and sulfonylurea is more effective, than drugs alone in enabling glycemic control in type 2 diabetes. However, safety of such combinations deserves further investigation. Keywords: Type2 diabetes mellitus, T2DM, drug related problems, sulfonylureas, biguanides.

Osteoporosis and diabetes mellitus (DM) are widespread diseases and have a significant health burden. Type-1 diabetes mellitus (T1DM) and Type-2 diabetes mellitus (T2DM) are associated with an increased bone fracture. In T1DM, the increased risk of bone fracture is associated with low bone mass. In patients with T2DM, the risk of fracture of the bone is increased due to low quality of bone, despite increased bone mineral density (BMD). In type 2 diabetic patients, bone fragility depends on the quality of bone instead of a reduction in bone mass. Thiazolidinediones (TZD) cause differentiation of adipocytes and inhibit differentiation of osteoblast and bone marrow stromal stem cells (BMSC). In this review, we have described the effect of anti-diabetic drugs and diabetes mellitus on bone health and our finding shows that sulfonylureas and metformin have no negative effect on bone health and protect bones against fractures.

Two series of novel NLRP3 inflammasome inhibitors are designed, synthesized, and evaluated in an effort to develop diversified analogs based on the N-(phenylcarbamoyl)benzenesulfonamide scaffold. SAR studies reveal that the sulfonylurea linker can tolerate chemical modifications with either simply changing over the position of carbonyl and sulfonyl group or structurally flexibly inserting a cyclopropyl group, leading to identification of several more potent and diversified NLRP3 antagonists (e.g., 9) with low nanomolar inhibitory activities. Further studies indicate that these two series of compounds with low cytotoxicity exhibited weak effects on the generation of NO and TNF-a. The findings may serve as good starting points for the development of more potent NLRP3 inflammasome inhibitors as valuable pharmacological probes or potential drug candidates.

Since their inception in the commercial market in the mid-twentieth century, sulfonylureas (SUs) have remained a therapeutic option in the management of type 2 diabetes (T2D). Despite their established glucose-lowering effects, there is no consensus among global experts and modern guidelines regarding the priority of SUs in relation to other therapeutic options, given the lack of evidence that SUs are associated with a low risk of macrovascular events and excess mortality. However, findings from recent trials and real-time observations have resolved this contentious issue somewhat, albeit to varying degrees. The present consensus discusses the role of SUs in contemporary diabetes management in the Gulf Cooperation Council (GCC) countries. Regional experts from these countries gathered virtually to formulate a consensus following presentations of topics relevant to SU therapy with an emphasis on gliclazide, including long-term efficacy, cost, end-organ benefits, and side effects, based on up-to-date evidence. The present narrative review reflects the conclusions of this assembly and provides a platform upon which future guidelines for the use of SUs in the GCC can be tailored.

Background: To verify whether, in patients on metformin (MET) monotherapy for type 2 diabetes (T2D), the add-on of a dipeptidyl peptidase inhibitor (DPP4i) compared to a sulfonylurea (SU) can delay the time to the subsequent treatment intensification (TI).Methods: Population-based administrative data banks from four Italian geographic areas were used. Patients aged ≥18 years on MET monotherapy receiving first DPP4i or SU dispensing between 2008 and 2015 (cohort entry) were followed up to the occurrence of TI (insulin dispensing or add-on of a third non-insulin hypoglicemic >180 days after cohort entry), treatment discontinuation, switch, cancer, death, TI occurrence within, end of data availability, end of study period (31 December 2016), whichever came first. Patients on MET + DPP4i were matched 1:1 with those on MET + SU by sex, age, year of cohort entry, and data bank. Hazard Ratio (HR) and 95% confidence intervals (95%CI) were estimated using multivariable Cox regression model including matching variables and potential confounders measured at baseline. Different sensitivity analyses were performed: i) matching at 180 days after cohort entry, ii) intent to treat (ITT) analysis, iii) matching by duration of MET monotherapy, iv) matching by propensity score.Results: The matched study cohort included 10,600 patients. Overall, 763 TI were observed (4.5/100 person-years; mean follow-up = 1.6 years). The primary analysis showed no difference in time to TI between the two groups (HR = 1.02; 95% CI = 0.88–1.19). Sensitivity analyses confirmed this result, except from the ITT analysis (HR = 1.27; 1.13–1.43).Conclusion: The use of a DPP4i rather than a SU as add-on to MET monotherapy was not associated with a delay in treatment intensification.

Sulfonylurea herbicides are widely used to control weeds due to their broad-spectrum activity and low animal toxicity. However, they have negative effects on environment. Microbial dioxygenases are...

Introduction VERTIS CV is the cardiovascular outcome trial for the sodium–glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin. A sub-study was conducted to assess the efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately glycemic-controlled on metformin and a sulfonylurea (SU). Methods Patients with T2DM, established atherosclerotic cardiovascular disease (ASCVD), and an HbA1c of 7.0–10.5% on stable metformin (≥ 1500 mg/day) and moderate to high SU doses were randomly assigned to once-daily ertugliflozin (5 or 15 mg) or placebo. The primary sub-study objectives were to assess the effect of ertugliflozin on HbA1c compared with placebo and to evaluate safety following 18 weeks of treatment. Key secondary endpoints included changes in fasting plasma glucose (FPG), body weight (BW), blood pressure (BP), and the proportion of patients achieving HbA1c

Two series of sulfonylureas derivatives including 24 compounds (4, 7, 5a–5o, 8a–8h), among them 17 new derivatives, have been synthesized and evaluated for their α-glucosidase inhibitory activity. Compounds 5c, 5h and 8e showed significant in vitro α-glucosidase inhibition with IC50 values of 5.58, 79.85 and 213.36 µm, respectively, comparing with the standard compounds acarbose (IC50 = 268.29 µm) and glipizide (IC50 = 300.47 µm). The preliminary structure-activity relationships (SARs) of the synthesized compounds were also investigated.

Introduction Neonatal diabetes mellitus (NDM) may be transient or permanent, and the majority is caused by genetic mutations. Early diagnosis is essential to select the patients who will respond to oral treatment. In this investigation, we aimed to present the phenotype and genotype of our patients with NDM and share our experience in a single tertiary center. Methods A total of 16 NDM patients from 12 unrelated families are included in the study. The clinical presentation, age at the diagnosis, perinatal and family history, consanguinity, gender, Hemoglobin A1c (HbA1c), C-peptide, insulin, insulin autoantibodies, genetic mutations, and response to treatment are retrospectively evaluated. Results The median age at diagnosis of diabetes was five months (4 days-18 months), 6 patients with a confirmed genetic diagnosis were diagnosed after 6 months. Three patients had KCNJ11 mutations, six had ABCC8 mutations, three had EIF2AK3 mutations, and one had a de novo INS mutation. All the permanent NDM patients with KCNJ11 and ABCC8 mutations were started on SU treatment resulting in a significant increase in C-peptide level, better glycemic control, and discontinuation of insulin. Conclusions Although NDM is defined as diabetes diagnosed during the first six months of life, and a diagnosis of type 1 diabetes is known much more common between the ages of 6 and 24 months, in rare cases it may present as late as 12 or even 24 months of age. Molecular diagnosis in NDM is important for planning treatment and predicting prognosis. Therefore, genetic testing is essential in these patients.

AIM: This research aims to compare the effectiveness of three medicines groups in controlling glycemic and glycated hemoglobin (HbA1c) levels in the newly diagnosed diabetes mellitus type 2. METHODS: One hundred fifty newly diagnosed patients with type 2 diabetes were treated by mono therapy and divided into three groups. Each group of 50 patients was treated by one medicine: Group 1 using Diamicron MR 30 mg (Sulfonylurea) – three capsules per day, Group 2 using metformin 500 mg – 1–3 capsules per day, and Group 3 using Januvia (sitagliptin, dipeptidyl peptidase-4 inhibitor) 100 mg – 1 capsule per day. The evaluation of glucose control was based on fasting plasma glucose and HbA1c concentration and divided into three levels: Excellent, good, and poor. The assessment was carried out after every 3 months of treatment, at 3rd month, 6th month, and 12th month (WHO, 2002). RESULTS: After treatment 3, 6, and 12 months, glucose level was decreased when compared to before treatment in all three groups (pall < 0.001). At the month 6th, the groups treated by sulfonylurea and sitagliptin had lower glucose level than metformin (with p values were 0.04 and 0.01, respectively), and maintained the low glucose level from the month 6th to month 12th (with p values were 0.71 and 0.77, respectively) while glucose level of the metformin group increased (p = 0.005). HbA1c has decreased dramatically in all three groups after treatment (p values of sulfonylurea group at the month 3rd, 6th, and 12th vs. before treatment were 0.006, 0.021, and 0.001, respectively; all p values of metformin group at the month 3rd, 6th, and 12th vs. before treatment were below 0.001; all p values of sitagliptin group at the month 3rd, 6th, and 12th vs. before treatment were below 0.001). The group treated by sitagliptin got the highest ratio of excellent HbA1c control (82% after 12 months of treatment). CONCLUSION: Significant improvement of glucose and HbA1c levels was observed in all three groups. Glucose control level of group treated with sulfonylurea was markedly improved and the group treated with sitagliptin achieved optimal control of HbA1c.

[Image: see text] Contemporary literature documents extensive research on common causative mechanisms, pathogenic pathways and dual effective remedies for Alzheimer’s disease (AD) and Type 2 diabetes mellitus (T2DM). Tolbutamide (TBM), chlorpropamide (CPM), and glyburide (GLY) are three sulfonylurea antidiabetic drugs of different generations. All these drugs were found to exhibit moderate to strong inhibitory efficiency on the neurotransmitter degrading enzyme acetylcholinesterase (AChE) with GLY (IC(50) = 0.74 ± 0.02 μM) being the most potent, followed by CPM (IC(50) = 5.72 ± 0.24 μM) and TBM (IC(50) = 28.9 ± 1.60 μM). Notably, the inhibition efficiency of GLY is even comparable with the FDA approved AD drug, donepezil (DON). The larger size of GLY spans almost the full gorge of AChE ranging from catalytic active site (CAS) to the peripheral active site (PAS) with relatively strong binding affinity (6.0 × 10(5) M(–1)) and acts as a competitive inhibitor for AChE. On the other hand, while they show relatively weak binding ((2–6) × 10(4) M(–1)), both CPM and TBM act as noncompetitive binders. While these two drugs can bind to PAS, MD simulation results predict an alternative noncompetitive inhibition mechanism for CPM. These results open the possibility of repurposing the antidiabetic drugs, particularly GLY, in the treatment of AD. The consequential side effect of excess acetylcholine production, due to the administration of these drugs to AD-unaffected patients, can be rectified by using colloidal gold and silver nanofluids as potential AChE activity boosters.

In this work the anion-binding properties of three aromatic sulfonylurea derivatives in acetonitrile and dimethyl sulfoxide were explored by means of NMR titrations. It was found that the studied receptors effectively bind anions of low basicity (Cl−, Br−, I−, NO3− and HSO4−). The stoichiometry of the complexes with receptors containing one binding site was 1 : 1 exclusively, whereas in the case of the receptor containing two sulfonylurea groups 1 : 2 (receptor : anion) complexes were also detected in some cases. The presence of strongly basic anions (acetate and dihydrogen phosphate) led to the deprotonation of the sulfonylurea moiety. This completely hindered its anion-binding properties in DMSO and only proton transfer occurred upon the addition of basic anions to the studied receptors. In MeCN, a complex system of equilibria including both ligand deprotonation and anion binding was established. Since ionisation of receptors was proven to be a decisive factor defining the behaviour of the sulfonylurea receptors, their pKa values were determined using several deprotonation agents in both solvents. The results were interpreted in the context of receptor structures and solvent properties and applied for the identification of the interactions with basic anions.

The efficacy and safety of medications can be affected by alterations in gut microbiota in human beings. Among antidiabetic medications, incretin-based therapy such as dipeptidyl peptidase 4 inhibitors might affect gut microbiomes, which are related to glucose metabolism. This was a randomized, controlled, active-competitor study that aimed to compare the effects of combinations of gemigliptin–metformin vs. glimepiride–metformin as initial therapies on gut microbiota and glucose homeostasis in drug-naïve patients with type 2 diabetes. Seventy drug-naïve patients with type 2 diabetes (mean age, 52.2 years) with a glycated hemoglobin (HbA1c) level ≥7.5% were assigned to either gemigliptin–metformin or glimepiride–metformin combination therapies for 24 weeks. Changes in gut microbiota, biomarkers linked to glucose regulation, body composition, and amino acid blood levels were investigated. Although both treatments decreased the HbA1c levels significantly, the gemigliptin–metformin group achieved HbA1c ≤ 7.0% without hypoglycemia or weight gain more effectively than did the glimepiride–metformin group (59% vs. 24%; p < 0.05). At the phylum level, the Firmicutes/Bacteroidetes ratio tended to decrease after gemigliptin–metformin therapy (p = 0.065), with a notable depletion of taxa belonging to Firmicutes, including Lactobacillus, Ruminococcus torques, and Streptococcus (all p < 0.05). However, regardless of the treatment modality, a distinct difference in the overall gut microbiome composition was noted between patients who reached the HbA1c target goal and those who did not (p < 0.001). Treatment with gemigliptin–metformin resulted in a higher achievement of the glycemic target without hypoglycemia or weight gain, better than with glimepiride–metformin; these improvements might be related to beneficial changes in gut microbiota.

Herbicide safeners enhance herbicide detoxification in crops without reducing their herbicidal efficacy against target weeds. To alleviate maize injury caused by the sulfonylurea herbicide nicosulfuron, a series of 1,3-disubstituted imidazolidine or hexahydropyrimidine derivatives were rationally designed via bioisosterism and active subunit combinations. Thirty novel compounds were synthesized using an efficient one-pot method and low-cost raw materials and characterized by IR, 1H NMR, 13C NMR, and high-resolution mass spectrometer (HRMS). Bioactivity and structure-activity relationship (SAR) were evaluated for herbicide safeners tested against nicosulfuron injury. Most of the compounds effectively protected sensitive maize against nicosulfuron damage. The parent skeletons and substituents of the target compounds both substantially influenced their safener activity. Compound I-3 exhibited superior bioactivity compared to the safener isoxadifen-ethyl. Molecular docking simulations disclosed that compound I-3 competed with nicosulfuron for the acetolactate synthase active site and demonstrated that this is the protective mechanism of safeners. The target compound I-3 presented with strong herbicide safener activity in maize and is, therefore, a potential candidate for the development of a novel herbicide safener.

The present study was to estimate the anti-diabetic and antihyperlipidemic activity of aqueous extract of leaves of plant Aloe barbadensis.In alloxan-induced diabetes in rats, the research examined six groups of six male wister rats every to value the hypoglycaemic effect of the barbadensis (ALEC) exposed to hostile to diabetic action in rodents where alloxan monohydrates were utilized as a portion of 120.00 mg/kg in intraperitoneal portion as a diabetogenic specialist to an acquainted diabetic with test rodents. In sub intense, treatment, bunch blood glucose levels are seen on 14.00th, 21.00th and 30.00th-day present treatment compare on typical control in diabetic control checked expanded blood glucose level was watched, with dosages of 100.00, 250.00 and 500.00 mg/kg b.w. A portion of 500.00 mg/kg b.w/day was seen as having the most significant activity. Glibenclamide was applied as a standard drug, and the outcome was compared about it. In the antihyperlipidemic activity, serum cholesterol levels were recorded at aqueous extracts of 100.00, 250.00 and 500.00 mg/kg, on 30.00th-day post-treatment. Serum cholesterol levels were ordinary benchmark groups was 107.70±01.21 mg/dl diabetic control 178.50±01.04 mg/dl and standard medications treatment bunches was 111.30±02.40 mg/dl and ALEC treatment bunches were 171.20±01.03 mg/dl, 145.80±02.92 mg/dl and 118.80±03.86 mg/dl for 100.00, 250.00 and 500.00 mg/kg separately. The results show that the aqueous extract of Aloe barbadensis has significant and continuous oral hypoglycaemic activity, equivalent to the hypoglycaemic result of glibenclamide, a sulfonylurea derivative and hyperlipidemic activity. Extracts also confirmed antihyperlipidaemic possible of the plant extract is establish to be comparable with that of the standard.

Despite the extensive efforts of physicians to achieve better control and management for blood glucose level in type 2 diabetics, maintaining near normal blood glucose level in these patients remain unsatisfactory. The objective of the study was to compare the effectiveness of sulfonylureas, metformin and combination of metformin plus sulfonylureas in controlling blood glucose in type 2 diabetics. Retrospective cohort research design conducted during the period of two months from 1st November 2019 to 1st March 2020 at Northern Area Armed Forces Hospital in Hafr Al Batin- Saudi Arabia on sample of 217 diabetic patients’ files, all data coded with serial number and analyzed by SPSS program through and inferential and descriptive statistics. Mean decrease in HbA1c for metformin therapy was 1.5(%), for sulfonylurea was 1.4(%), for combination therapy was 1.9(%). Mean decrease in HbA1c fasting blood glucose for metformin therapy was 1.8(mmol/l), for sulfonylurea was 1.6(mmol/l), for combination therapy was 3(mmol/l). Mean decrease in postprandial blood glucose for metformin therapy was 3.2(mmol/l), for sulfonylurea therapy was 3(mmol/l), for combination therapy was 3.7(mmol/l). There was a significant difference between levels of HbA1c between metformin group and combination group (metformin and sulfonylurea) (p = 0.002) and also there was a significant difference between sulfonylurea group and combination group (metformin and sulfonylurea) in relation to HbA1c levels (p = 0.001). However, there was no significant difference between metformin and sulfonylurea in decreasing HbA1c (p = 0.09). In conclusion, metformin or sulfonylurea as a single therapy is similar in efficacy in reducing glycosylated hemoglobin level, fasting and post-prandial plasma glucose levels to equal degree. However, combination of both therapies resulted in significant greater control of blood glucose level.

A soybean trait resistant to sulfonylurea herbicides along with glyphosate (Bolt™ soybean) has been developed. Information is needed to determine herbicide programs for weed control and crop safety in this new multiple herbicide–resistant soybean trait. The objectives of this study were to evaluate weed control and crop safety in sulfonylurea/glyphosate-resistant soybean with herbicide programs, including but not limited to acetolactate synthase (ALS) inhibitors. Field experiments were conducted near Clay Center, NE, USA, in 2016 and 2017. Herbicide programs with multiple sites-of-action including rimsulfuron/thifensulfuron in mixture with flumioxazin, flumioxazin/chlorimuron, pyroxasulfone, chlorimuron/metribuzin, or saflufenacil/imazethapyr plus dimethenamid-P provided 91%–97% control of common waterhemp, velvetleaf, and common lambsquarters. Rimsulfuron and (or) thifensulfuron resulted in 92%–97% control of velvetleaf and common lambsquarters and 81%–87% common waterhemp control at 21 d after pre-emergence (PRE) (DAPRE) herbicide application. Soybean injury was transient and varied from 3% to 11% at 21 DAPRE and 14 d after post-emergence (POST) (DAPOST) herbicide application without causing yield loss. At 30 and 60 DAPOST, 87%–97% velvetleaf control and 92%–98% common lambsquarters control was achieved with herbicide programs tested (PRE, POST, or PRE followed by POST). Common waterhemp control at 30 and 60 DAPOST was not consistent between years. Weed density and biomass reduction were mostly similar to weed control achieved. Untreated control resulted in the lowest soybean yield (1811 kg ha−1) in 2016 compared with 3406–4611 kg ha−1 in herbicide programs.

OBJECTIVE ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of ABCC8-PNDM and ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. RESEARCH DESIGN AND METHODS We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analyzed using nonparametric statistical methods. RESULTS Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1–13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfonylurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P = 0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P = 0.04), n = 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P = 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%). CONCLUSIONS Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.

To find new sulfonylurea inhibitors with high efficacy and fast hydrolysis degradation rate, a few compounds were first designed based on the commercial product Chlorimuron-Ethyl (CE) by estimating the binding interaction between the inhibitor and the Acetohydroxyacid Synthase (AHAS) using the quantum mechanical approach. Meanwhile, the activation energy barriers of hydrolysis for the sulfonylurea inhibitors with the amino and nitro groups onto para position of the benzene ring were calculated. Based on the calculated binding interaction energy and hydrolysis energy barrier, six new sulfonylurea inhibitors I1–I6 were designed and synthesized. By measuring the half-lives through hydrolysis degradation assay, it was indicated that the compounds I1–I3 with the introduction of an amino group at the fourth position of benzene ring show much faster degradation rate than those compounds with nitro groups, which is in a good agreement with the calculated results for hydrolysis barrier. The herbicide activity tests show that the compounds I1 and I2 remained excellent herbicidal activity on both broadleaf weeds with soil treatment at a concentration about 150[Formula: see text]mg/l. Due to their short half-lives of chemical hydrolysis and high herbicidal activities, compounds I1 and I2 could be potential herbicidal candidates in the future, which are helpful for the sustainable development of the environment and ecology.

The esterase SulE is known to be an important and primary enzyme for the degradation of many sulfonylurea herbicides such as tribenuron-methyl, metsulfuron-methyl, and chlorimuron-ethyl. The disadvantages of applying free enzyme include poor stability and rapid deactivation in the natural environment, but these problems can be mitigated by using immobilized enzymes. In this study, cross-linked gelatin/chitosan (GLT/CTS) was selected as the enzyme immobilization carrier because its SulE activity recovery was higher than those of γ-polyglutamate/gelatin (γ-PGA/GLT) and γ-polyglutamate/chitosan (γ-PGA/CTS). The immobilization conditions were further optimized, and the effects of pH and temperature on GLT/CTS-SulE and free SulE activities to degrade tribenuron-methyl and metsulfuron-methyl were investigated. A microcosm experiment was conducted to assess the effectiveness of GLT/CTS-SulE in remediating soils polluted with tribenuron-methyl and metsulfuron-methyl. The results showed that, compared with free SulE, GLT/CTS-SulE displayed better pH and temperature adaptabilities and higher degradation efficiencies for both herbicides in soil, especially tribenuron-methyl. The results indicate that this is an excellent method to immobilize SulE for enhanced remediation of soils polluted with tribenuron-methyl or metsulfuron-methyl in situ.

Sulfonylureas are widely used in patients with type 2 diabetes; meanwhile, the increasing fractures risks especially in the old are gradually taken into consideration. This meta-analysis aimed at investigating whether sulfonylureas could influence the risk of fractures in type 2 diabetes (T2DM) in the elder patients (≥ 65 years old). We searched the PubMed and other databases to screen eligible studies. Two authors independently extracted data according to the selection criteria for each study. The Newcastle–Ottawa scale was used to evaluate the quality. Subgroups and sensitivity analyses were performed and publication bias was assessed. A total of 7 studies involving 464,121 individuals were included in our meta-analysis. The pooled risk ratio for developing fracture in sulfonylurea users with type 2 diabetes (≥ 65 years old) was 1.26 (95% CI 1.15–1.39). Sensitivity analyses confirmed the stability of the results and there was no publication bias. Sulfonylureas could add the risk of fractures among the old with type 2 diabetes. Initial sulfonylureas therapy in both men and women should be done prudently.

In the framework of this research, four new herbicidal ionic liquids (HILs) comprising chlorsulfuron as the anion were synthesized and characterized. The new salts with chlorsulfuron contained the following cations: tetramethylammonium, didecyldimethylammonium, benzyltrimethylammonium and cholinium. All products were obtained with high yields exceeding 90% via acid–base reaction or ion exchange reaction, by the use of environment-friendly solvents. The structures of all synthesized HILs were confirmed by FT-IR, 1H NMR and 13C NMR analyses. Their efficacy against weeds has been studied under field conditions in fiber flax. All HILs showed herbicidal activity but efficiency was highly dependent on the type of cation and weed species. There were no statistically significant differences in the effectiveness of HILs toward common lambsquarters compared to the reference herbicide, except for salt with cholinium cation that showed significantly lower efficiency. As regards barnyard grass control, all HILs exhibited significantly lower efficacy than that of the reference herbicide, except for didecyldimethylammonium salt that showed similar activity. The synthesized products did not cause damage to flax plants. The obtained results confirmed that the herbicidal effectiveness of the active ingredient (chlorsulfuron) in the form of an ionic liquid can be adjusted by the selection of an appropriate cation in the synthesis.

Objectives Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life. Case presentation We report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up. Conclusions This report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

Hypoglycemia related to treatment of type 2 diabetes mellitus patients constantly represents a substantial problem. It is connected with higher mortality and lower quality of life, mostly displayed with elder patients. Therefore it is vital to revise the antidiabetic therapy regularly and to inquire for the associated risks. Nevertheless, elder patiens are often following the inadvisable treatment by sulphonylureas derivates, which represent the second most risky medication causing hypoglycemia after insulin. In our retrospective study we analysed the occurence of serious hypoglycemia, caused by any factor, with severe diabetics urgently hospitalised at The Department of Internal Medicine of Masaryk Hospital in Usti nad Labem, in relation to the applied antidiabetic therapy. We suspected a negative influence of hypoglycemizing therapy (above all sulphonylureas) with the elderly patiens. In sum, we hospitalised 32 patients with type 2 diabetes mellitus (average age 76,5 ± 8,2 years), 18 of these using sulphonylureas (average age 77,4, with a relatively wide range from 65 to alarming 93 years). The average figure of estimated glomerular filtration rate (eGFR) was 0,745 (±0,293) ml/s/1,73m2. Moreover, the patients manifested polmorbidity - the average of comorbidities was 3,125, and even 3,5 with patiens on sulphonylureas. Following the arguments summarised above, we believe that hypoglycemic episodes are extremely dangerous especially for elder patients with T2DM, and from this point of view, the medication using sulphonylureas derivates seems to be inappropriate.

Background. Endothelin (ET) is one of the most significant regulators of the functional state of vascular endothelium. ET‑1 is the principal cardiovascular isoform of the endothelin system. ET‑1 has both inflammatory and proliferative affects and contributes to pathogenic processes in the cardiovascular system. In diabetes, the rise of glucose concentration effects the formation of ET‑1. The aim of the work was to study the content of ET‑1 in the blood of patients with diabetes treated with various hypoglycemic agents. Material and methods. The amount of ET‑1 was evaluated via ELISA in 103 individuals: 17 healthy volunteers and 86 patients with diabetes. To determine the concentration of ET‑1 the endothelin (1-21) EIA kit (Biomedica) was used. Glycated hemoglobin wasdetermined using one HbA1c FS kit — DiaSys Diagnostic Systems. Results. The average level of endothelin in the blood of patients with diabetes was 0.536±0.047 fmol/ml vs. control — 0.118±0.017 fmol/ml. We did not observed changes of ET‑1 levels during monotherapy with metformin or insulin. At metformin + insulin + dapagliflosin, insulin + metformin and sulfonylurea + metformin but not DPP‑4 inhibitor + metformin combinations (T2D) there was decrease of ET‑1 level in the blood. It is of interest that DPP‑4 inhibitor + metformin caused significant increase (0.767±0.043 fmol/ml) of ET‑1 concentration. Conclusion. Thus, with combination therapy, except pair DPP‑4 inhibitor + metformin, the level of ET‑1 in the blood of patients with diabetes decreased significantly more than with monotherapy.

Despite the long-term renoprotective effects of Metformin, a recent study on data from the U.S. Food and Drug Administration reported a possible nephrotoxic effect, contributing to the development of acute kidney injury (AKI). We investigated the association between metformin and AKI in patients admitted with the AKI-prone condition of acute infection and compared results with corresponding results of other antidiabetics. In a nationwide register-based case–control study, we identified Danish patients with type 2 diabetes hospitalized with acute infection between 2008 and 2018. Cases of AKI had an increase in plasma creatinine ≥ × 1.5 during admission, controls did not. Antidiabetics were identified up to 6 months before admission. Odds ratio (OR) of each antidiabetic was computed in separate multiple logistic regression models adjusted for relevant medication and comorbidities and results compared. We included 46,811 patients, hereof 9454 AKIs (20%) and 2186 (4.7%) severe AKIs. Overall, 56% were males, median age (IQR) was 73 (65–81). Sixty percent received metformin, 13% sulfonylurea, 31% insulin and 8% dipeptidyl peptidase-4 inhibitors (DPP-4i), with equal distribution between cases and controls. Metformin was associated with increased OR (CI) for AKI, 1.07 (1.02–1.12), equally to sulfonylurea, 1.10 (1.03–1.18) and DPP-4i, 1.11 (1.02–1.20), but not insulin, 0.99 (0.93–1.05). In severe AKI, results for metformin were 1.27 (1.25–1.40) but increased equivalently to other antidiabetics. In patients with type 2 diabetes hospitalized with acute infection, metformin was not independently associated with AKI, since other antidiabetics were also significantly associated, indicating confounding by indication.

Objective. Mutations of the KCNJ11 gene are the most common cause of the permanent neonatal diabetes mellitus (PNDM). Majority of people with KNCJ11-PNDM have a de-novo mutation. We aimed to compare diabetes phenotype in two children and their mothers with PNDM carrying the same sulfonylurea-sensitive KCNJ11 variants. Methods. We have compared glibenclamide (sulfonylurea) dose, C-peptide, and HbA1c serum levels in two children and their mothers with PNDM up to 5.5-year follow-up. All of them were carrying a heterozygous activating KCNJ11 pathogenic variant (p.R201H in Family 1 or p.H46Y in Family 2). The mothers were initially treated with insulin and successfully switched to sulfonylurea at the age of 24 and 11 years, respectively. Both children were treated with sulfonylurea since the diagnosis of PNDM. Results. Glibenclamide dose was similar in both children (0.02–0.03 mg/kg/day), but lower compared to their mothers (0.1–0.4 mg/kg/day) (p Conclusions. Evaluation of the treatment in people with sulfonylurea-sensitive KNCJ11-PNDM should respect the age of patients together with the type of mutation and duration of diabetes at therapy start and may differ within one family.

OBJECTIVE To examine the comparative effectiveness of sodium–glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP-1), dipeptidyl peptidase 4 inhibitors (DPP-4), and sulfonylureas on risk of kidney outcomes among people with type 2 diabetes. RESEARCH DESIGN AND METHODS U.S. veterans initiated on SGLT2i (n = 18,544), GLP-1 (n = 23,711), DPP-4 (n = 39,399), or sulfonylureas (n = 134,904) were followed for up to 3 years to evaluate the risk of the composite outcome of estimated glomerular filtration rate (eGFR) decline >50%, end-stage kidney disease (ESKD), or all-cause mortality. Risks were estimated using survival models adjusted for predefined covariates as well as covariates identified by a high-dimensional variable selection algorithm through application of generalized propensity scores. RESULTS Compared with those treated with sulfonylureas, treatment with SGLT2i, GLP-1, and DPP-4 was associated with a lower risk of the composite outcome (hazard ratio 0.68 [95% CI 0.63, 0.74], 0.72 [0.67, 0.77], and 0.90 [0.86, 0.95], respectively). While we did not observe a statistically significant difference in risk between the SGLT2i and GLP-1 arms (0.95 [0.87, 1.04]), both SGLT2i and GLP-1 had a lower risk of the composite outcome than DPP-4 (0.76 [0.70, 0.82] and 0.79 [0.74, 0.85], respectively). Analyses by eGFR category suggested that compared with the sulfonylurea arm, those in the SGLT2i and GLP-1 arms exhibited a lower risk of the composite outcome in all eGFR categories, including eGFR CONCLUSIONS In type 2 diabetes, treatment with SGLT2i or GLP-1 compared with DPP-4 or sulfonylureas was associated with a lower risk of adverse kidney outcomes.

Background: The vast majority of individuals diagnosed with diabetes are low/middle income and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost: metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide, glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or dose-related. Objective: We conducted a narrative review of low-cost OHMs. Results: We evaluated the maximum recommended (MAX) compared to the most effective (EFF) daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic medications. Results: We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000 mg, EFF: 1,500–2,000/1,500–2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide (MAX: 20 mg, EFF: 2.5–5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in HbA1c levels occurred at weeks 12–20 (sulfonylureas), 25–39 (metformin), and 25 (pioglitazone). Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses (p Conclusion: Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.

Introduction Few studies have examined memory decline among patients with type 2 diabetes using different oral hypoglycemic drugs. Methods Participants with normal cognition (NC) or Alzheimer's disease (AD) dementia using a hypoglycemic medication (2005 to 2019) were identified from the National Alzheimer's Coordinating Center database. Delayed memory was assessed using the Wechsler Memory Scale Revised–Logical Memory test. Associations between oral drug classes and memory over time were examined using mixed‐effects models with inverse probability treatment weights. Results In NC (n = 1192), metformin use was associated with better memory performance over time, whereas in AD (n = 807), dipeptidyl peptidase‐4 (DPP4) inhibitor use was associated with a slower rate of memory decline. Interaction effects suggested greater benefit associated with DPP4 inhibitor use among APOE ε4 carriers. Discussion Associations between different oral hypoglycemic drugs and memory change were not consistent between cognitively normal elderly and those with AD dementia. APOE ε4 genotype modified some relationships.

A precision medicine approach is used to improve treatment of patients with monogenic diabetes. Herein, we searched SU efficiency according to the genotype-phenotype correlation, dosage used, and side effects.Systematic review conducted according the PRISMA control criteria identifying relevant studies evaluating the in vivo and in vitro sensitivity of ATP-dependent potassium channels according to the characteristics of genetic mutation.Hundred and three selected articles with complete data in 502 cases in whom 413 (82.3%) had mutations in KCNJ11 (#64) and 89 in ABCC8 (# 56). Successful transfer from insulin to SU was achieved in 91% and 86.5% patients, respectively, at a mean age of 36.5 months (0-63 years). Among patients with KCNJ11 and ABCC8 mutations 64 and 46 were associated with constant success, 5 and 5 to constant failure, and 10 and 4 to variable degrees of reported success rate, respectively. The glibenclamide dosage required for each genotype ranged from 0.017 to 2.8 mg/kg/day. Comparing both the in vivo and in vitro susceptibility results, some mutations appear more sensitive than others to sulfonylurea treatment. Side effects were reported in 17/103 of the included articles: mild gastrointestinal symptoms and hypoglycaemia were the most common. One premature patient had an ulcerative necrotizing enterocolitis which association with SU is difficult to ascertain.Sulfonylureas are an effective treatment for monogenic diabetes due to KCNJ11 and ABCC8 genes mutations. The success of the treatment is conditioned by differences in pharmacogenetics, younger age, pharmacokinetics, compliance, and maximal dose used.