Introduction: Clinically important drug–drug interactions are a frequently overlooked cause of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM). Gliclazide is primarily metabolized via cytochrome P450 2C9 (CYP2C9), while fluconazole is a potent inhibitor of this enzyme.1,2 Concomitant administrations markedly increase gliclazide plasma concentration and prolong its hypoglycemic effect, substantially increasing the risk of severe and prolonged hypoglycemia. In some cases of refractory sulfonylureainduced hypoglycemia, octreotide may need to be considered early. Case: A 63-year-old Malay female with a 15-year history of T2DM on maximum-dose gliclazide (320 mg/day) presented with syncope and recurrent severe hypoglycemia 5 days after receiving a single oral dose of fluconazole 150 mg for a superficial fungal skin infection. Her other antidiabetic medications included metformin 1 g twice daily and vildagliptin 50 mg once daily. Her blood pressure on presentation was 151/74 mmHg, and her glucose level was 2.8 mmol/L. Her presentation was compounded by community-acquired pneumonia and acute kidney injury (estimated glomerular filtration rate 52 mL/min/1.73 m²). Biochemical evaluation excluded adrenal insufficiency, with normal serum cortisol (1,098 µg/dL), serum sodium (141 mmol/L), and serum potassium (4.6 mmol/L). Thyroid and liver function tests were normal. Despite repeated boluses of 50% dextrose and continuous infusion of 20% dextrose, recurrent hypoglycemia persisted for up to 48 hours after discontinuation of gliclazide, with glucose ranging from 1.7 to 5.1 mmol/L, reflecting prolonged sulfonylurea activity. Conclusion This case highlights a clinically significant yet preventable interaction between fluconazole and gliclazide, mediated through CYP2C9 inhibition, resulting in sustained hyperinsulinemic hypoglycemia. Gliclazide should be reduced or withheld prior to initiating fluconazole, and medication review should be performed at every consultation.
Fluconazole ; Gliclazide ; Hypoglycemia

Introduction: Sulfonylureas (SUs) are commonly used drugs for type 2 diabetes mellitus (T2DM) in the Philippines. This study aimed to associate genetic variants with poor response to gliclazide and glimepiride among Filipinos. Methodology: Two independent, dichotomous longitudinal substudies enrolled 139 and 113 participants in the gliclazide and glimepiride substudies, respectively. DNA from blood samples underwent customized genotyping for candidate genes using microarray. Allelic and genotypic features and clinical associations were determined using exact statistical methods. Results: Three months after sulfonylurea monotherapy, 18 (13%) were found to be poorly responsive to gliclazide, while 7 (6%) had poor response to glimepiride. Seven genetic variants were nominally associated (p<0.05) with poor gliclazide response, while three variants were nominally associated with poor glimepiride response. For gliclazide response, carboxypeptidase-associated variants (rs319952 and rs393994 of AGBL4 and rs2229437 of PRCP) had the highest genotypic association; other variants include rs9806699, rs7119, rs6465084 and rs1234315. For glimepiride response, 2 variants were nominally associated: CLCN6-NPPA-MTHFR gene cluster – rs5063 and rs17367504 – and rs2299267 from the PON2 loci. Conclusion Genetic variants were found to have a nominal association with sulfonylurea response among Filipinos. These findings can guide for future study directions on pharmacotherapeutic applications for sulfonylurea treatment in this population.
genetic variants ; sulfonylureas ; Filipino ; gliclazide

BACKGROUND: Previous studies have noted that the simultaneous use of sulfonylureas and antimicrobials, which is common, could increase the risk of hypoglycemia. In particular, an age of 65 years or older is a known risk factor for sulfonylurea-related hypoglycemia in hospitalized patients. Therefore, we performed this study to determine the potential risk of hypoglycemia from the concurrent use of antimicrobials and sulfonylureas. METHODS: We performed a cross-sectional study on the National Health Insurance Service-National Sample Cohort from 2013. The eligibility criteria included patients of 65 years of age or older taking a sulfonylurea with 25 different antimicrobials. Different risk ratings of severity in drug-drug interactions (potential DDIs), level X, D, or C in Lexi-Interact™online, and contraindicated, major, or moderate severity level in Micromedex® were included. SAS version 9.4 was used for data analysis. RESULTS: A total of 6,006 elderly patients with 25,613 prescriptions were included. The largest age group was 70 to 74 (32.7%), and 39.7% of patients were men. The mean number of prescriptions was 4.3 per patient. The most frequently used antimicrobials were levofloxacin (6,583, 25.7%), ofloxacin (6,549, 25.6%), fluconazole (4,678, 18.0%), and ciprofloxacin (2,551, 9.8%). Among sulfonylureas, glimepiride was prescribed most frequently, followed by gliclazide, glibenclamide, and glipizide. CONCLUSION: Of the antimicrobials with a high potential of hypoglycemia, levofloxacin, ofloxacin, fluconazole, and ciprofloxacin were used frequently. Thus, the monitoring of clinically relevant interactions is required for patients concurrently administered sulfonylureas and antimicrobials.
Aged* ; Anti-Infective Agents ; Ciprofloxacin ; Cohort Studies ; Cross-Sectional Studies ; Drug Interactions ; Fluconazole ; Gliclazide ; Glipizide ; Glyburide ; Humans ; Hypoglycemia* ; Korea* ; Levofloxacin ; Male ; National Health Programs ; Ofloxacin ; Prescriptions ; Risk Factors ; Statistics as Topic ; Sulfonylurea Compounds

Permanent neonatal diabetes mellitus (PNDM) is caused by mutations in the ATP-sensitive potassium channel (K(ATP) channel) subunits. Developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome is the most severe form of PNDM and is characterized by various neurologic features. We report on a patient with DEND syndrome following initial misdiagnosis with type 1 DM, who was successfully switched from insulin to sulfonylurea therapy. A 50-day-old male presented with fever and seizure, complicated by persistent hyperglycemia. Insulin therapy was initiated. At 10 months of age, the patient was unable to hold his head up and make eye contact with others. At 17.9 years of age, direct sequencing of KCNJ11 identified a heterozygous mutation of c.602G>A (p.R201H). Since then, treatment with gliclazide was initiated and the insulin dose was gradually reduced. Following 3 months, insulin was discontinued with a gliclazide dose of 2.4 mg/kg. The patient continued to have excellent glycemic control with a glycated hemoglobin (HbA1c) level of 5.8% after 5 months. However, the patient's psychomotor retardation did not improve. This study reports the first case of DEND syndrome in Korea caused by a KCNJ11 mutation and emphasizes the necessity to screen mutations in KATP channel genes in patients with neonatal diabetes.
Diabetes Mellitus ; Diagnostic Errors ; Epilepsy ; Fever ; Gliclazide ; Head ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia ; Insulin ; Korea ; Male ; Potassium Channels ; Seizures

OBJECTIVETo compare the roles of alisma and gliclazide in the treatment of diabetes in Goto-Kakizaki (GK) rats.

METHODSGK rats were randomly divided into alisma group, gliclazide group, and blank group, and Wistar rats were used as the normal group. After two weeks of treatment, body weight, food intake,fasting glucose, impaired glucose tolerance, and other indicators were measured.

RESULTSThe body weight increased after the treatment in the normal group,blank group,and gliclazide group [(241.3 ± 7.0)g vs.(263.5 ± 11.1)g, (242.8 ± 7.1)g vs.(267.9 ± 16.8)g, (243.9 ± 12.2)g vs.(277.9 ± 9.8)g, P<0.05] but decreased in alisma group [(244.6 ± 9.2)g vs.(227.9 ± 13.7)g, P<0.05]. The food intake showed no significant change before and after administration among different groups(P>0.05). Fasting glucose was significantly lower in normal group than in control group,alisma group,and gliclazide group [(4.8 ± 0.2) mmol/L vs.(8.2 ± 1.4) mmol/L,(8.1 ± 0.6) mmol/L, (8.1 ± 0.9)mmol/L, P<0.05] one week after drug administration; it was not significantly different among blank group,alisma group,and gliclazide group before drug administration (P>0.05); however, it significantly decreased in alisma group and gliclazide group two weeks after administration [(6.9 ± 0.7) mmol/L vs.(8.1 ± 0.6) mmol/L; (5.8 ± 0.5) mmol/L vs.(8.1 ± 0.9) mmol/L, P<0.05]; compared with the blank group, the fasting glucose was significantly lower in the alisma group and gliclazide group,and it was also significantly different between these two groups [(6.9 ± 0.7) mmol/L vs.(8.8 ± 0.6) mmol/L,(5.8 ± 0.5)mmol/L vs.(8.8 ± 0.6)mmol/L, (6.9 ± 0.7) mmol/L vs.(5.8 ± 0.5)mmol/L, P<0.05]. Compared with the normal group,glucose tolerance was abnormal in blank group,alisma group,and gliclazide group;after two weeks of treatment,glucose tolerance was significantly improved in alisma group (P<0.05); compared with the pretreatment level and that in the blank group,the glucose tolerance in gliclazide group showed no significant difference (P> 0.05).

CONCLUSIONSBoth alisma and gliclazide monotherapy is effective in lowering fasting blood glucose. As a single-target drug,gliclazide has stronger effecacy in lowering fasting glucose. However, alisma, as a mixture, can also control weight and improve glucose intolerance.

Alisma ; Animals ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Experimental ; Gliclazide ; Rats ; Rats, Wistar

To establish the parsimonious model for blood glucose monitoring in patients with type 2 diabetes receiving oral hypoglycemic agent treatment. One hundred and fifty-nine adult Chinese type 2 diabetes patients were randomized to receive rapid-acting or sustained-release gliclazide therapy for 12 weeks. Their blood glucose levels were measured at 10 time points in a 24 h period before and after treatment, and the 24 h mean blood glucose levels were measured. Contribution of blood glucose levels to the mean blood glucose level and HbA1c was assessed by multiple regression analysis. The correlation coefficients of blood glucose level measured at 10 time points to the daily MBG were 0.58-0.74 and 0.59-0.79, respectively, before and after treatment (P<0.0001). The multiple stepwise regression analysis showed that the blood glucose levels measured at 6 of the 10 time points could explain 95% and 97% of the changes in MBG before and after treatment. The three blood glucose levels, which were measured at fasting, 2 h after breakfast and before dinner, of the 10 time points could explain 84% and 86% of the changes in MBG before and after treatment, but could only explain 36% and 26% of the changes in HbA1c before and after treatment, and they had a poorer correlation with the HbA1c than with the 24 h MBG. The blood glucose levels measured at fasting, 2 h after breakfast and before dinner truly reflected the change 24 h blood glucose level, suggesting that they are appropriate for the self-monitoring of blood glucose levels in diabetes patients receiving oral anti-diabetes therapy.
Adult ; Blood Glucose ; drug effects ; Blood Glucose Self-Monitoring ; methods ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Gliclazide ; therapeutic use ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemia ; chemically induced ; Hypoglycemic Agents ; therapeutic use ; Male ; Models, Biological

OBJECTIVETo perform meta-analyses evaluating the efficacy of adding Liuwei Dihuang Pills (, LDP) to Western medicine in improving treatment outcomes for type 2 diabetes.

METHODSMedline, PubMed, Cochrane Library, and Chinese databases, including the Chinese National Knowledge Infrastructure were searched to identify eligible studies; i.e., if the study involved a randomized clinical trial in which the experimental group combined LDP with Western drugs and the control group used the corresponding Western drugs alone to treat type 2 diabetes. Outcomes were measured in terms of fasting blood glucose (FBG), postprandial blood glucose (2hPG) and HbA1c level. Efficacy was also measured by using control and response rates. The combined odds ratio (OR), mean difference (MD), and 95% confidence intervals (95% CI) were calculated.

RESULTSStudies included in the analysis were less adequate than expected in terms of methodological quality. A total of 1,609 patients from 18 studies were included. We found that adding LDP can lower patients' FBG (MD=0.54 mmol/L, 95% CI [0.15, 0.93], P=0.007), 2hPG (MD=1.05 mmol/L, 95% CI [0.29, 1.81], P<0.01) and HbA1c (MD=0.23, 95% CI [0.02, 0.45], P=0.008). There were also improvements in treatment response rates (OR=3.41, 95% CI [2.38, 4.90], P<0.01) and control rates (OR=2.47, 95% CI [1.91, 3.20], P<0.01).

CONCLUSIONAdding LDP to Western medicine might improve treatment outcomes of diabetes, including FBG, 2hPG, response rates and control rates.

Blood Glucose ; metabolism ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Fasting ; blood ; Gliclazide ; adverse effects ; therapeutic use ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Metformin ; adverse effects ; therapeutic use ; Publication Bias ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Western World

BACKGROUND: Diabetes mellitus (DM) is one of the most important chronic diseases in public health, thus optimal management of this condition is crucial. For this purpose, oral hypoglycemic agents (OHA) are commonly prescribed with their consistent use being mandatory to maintain adequate blood glucose levels. We aimed to evaluate the compliance with OHA in patients with DM, and to determine the factors associated with compliance. METHODS: From March 2006 to December 2007, we enrolled patients with type 2 DM who were newly diagnosed or had discontinued OHAs for more than four weeks. For OHA, diamicron was prescribed to the participants and response to medication was evaluated by physicians after 12 weeks. Compliance was defined as patients taking diamicron continuously or stopping the medication due to well-controlled blood sugar levels. Demographic characteristics, anthropometric measurements, fasting glucose, and lipid profiles were collected and analyzed. RESULTS: The mean age of our 326 subjects was 56.0+/-9.9 years and 74.5% was defined to be compliant. Logistic regression analysis adjusting for age and sex revealed that combined medication use (odd ratio [OR], 2.03; 95% confidence interval [CI], 1.04-3.97) and diabetes-related nutritional education (OR, 2.08; 95% CI, 1.08-4.03) (P<0.05) were factors associated with compliance with OHA. CONCLUSIONS: About three quarters of the DM patients in our study, using diamicron for the first time, showed compliance after 12 weeks of treatment. Concomitant medications and diabetes-related nutrition education were associated with compliance.
Blood Glucose ; Chronic Disease ; Compliance* ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Education ; Fasting ; Gliclazide* ; Glucose ; Humans ; Hypoglycemic Agents ; Logistic Models ; Patient Education as Topic ; Public Health

BACKGROUNDBoth repaglinide and gliclazide are insulin secretagogues widely used in the treatment of type 2 diabetes. They stimulate insulin secretion through distinct mechanisms and may benefit patients from different aspects. The present study was to evaluate the effects of repaglinide or gliclazide on glycaemic control, insulin secretion, and lipid profiles in type 2 diabetes patients.

METHODSA total of 47 newly diagnosed type 2 diabetes patients were randomized 1:1 to receive a 4-week treatment with repaglinide or gliclazide. The standard mixed meal tolerance test was performed before and after the treatment. Plasma glucose (PG), insulin concentration, and lipid profiles were measured. The area under insulin concentration curve (AUC(ins)) and the early-phase insulin secretion index (ΔI(30)/ΔG(30)) were calculated.

RESULTSAfter the trial, fasting and postprandial PG and postprandial insulin improved significantly in both groups (P < 0.05). The maximum insulin concentration occurred earlier in the repaglinide group than that in the gliclazide group. AUC(ins) increased in both groups (P < 0.05), but no significant difference was found between groups. ΔI(30)/ΔG(30) increased in both groups (P < 0.05), especially in the repaglinide group (P < 0.05). Triglyceride and total cholesterol decreased significantly in the repaglinide group in some time points, while no significant change was observed in the gliclazide group.

CONCLUSIONSRepaglinide and gliclazide had similar effects on glycaemic control and total insulin secretion, while repaglinide had more effects on improvements in β-cell function and lipid metabolism.

Adult ; Blood Glucose ; drug effects ; Carbamates ; therapeutic use ; Cholesterol ; blood ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; metabolism ; Fasting ; blood ; Female ; Gliclazide ; therapeutic use ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin ; secretion ; Male ; Middle Aged ; Piperidines ; therapeutic use ; Postprandial Period ; drug effects ; Treatment Outcome ; Triglycerides ; blood

BACKGROUND: To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects. METHODS: We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009. RESULTS: A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69+/-12 years, mean duration of diabetes was 13.8+/-9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users. CONCLUSION: We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.
Adult ; C-Peptide ; Emergencies ; Gliclazide ; Hospitals, General ; Humans ; Hypoglycemia ; Insulin ; Korea ; Renal Insufficiency, Chronic ; Sulfonylurea Compounds