ao-128 and Hypoglycemia

Topics: 1-Deoxynojirimycin; Acarbose; Digestive System Diseases; Drug Interactions; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperammonemia; Hypoglycemia; Hypoglycemic Agents; Imino Pyranoses; Inositol

Topics: Acarbose; Chemical and Drug Induced Liver Injury; Contraindications; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Dyspepsia; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperammonemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Patient Selection

Topics: Acarbose; Administration, Oral; Animals; Biguanides; Cardiovascular System; Chromans; Drug Interactions; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin Resistance; Sulfonylurea Compounds; Thiazoles; Thiazolidinediones; Trisaccharides; Troglitazone

Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy.. This cross-over trial included 20 patients with type 2 diabetes. After initiating vildagliptin 100 mg, patients were randomly assigned to receive mitiglinide 10 mg/voglibose 0.2 mg three times daily for 3 days followed by glimepiride 1 mg once daily for the subsequent 3 days as add-on therapy, or vice versa. Glucose excursions and hypoglycemia frequency were measured using 24-h continuous glucose monitoring. Metabolic profile changes were evaluated using a meal tolerance test.. The mean glucose levels in the mitiglinide/voglibose and glimepiride phases were identical (8.01 vs 8.24 mmol/L, respectively). However, during the mitiglinide/voglibose phase compared with the glimepiride phase, the standard deviation of glucose (1.30 vs 2.10 mmol/L; P < 0.001), mean amplitude of glycemic excursions (3.47 vs 5.28 mmol/L; P < 0.001), M-value (24.6 vs 70.0; P < 0.001), continuous overlapping net glycemic action for a 1-h time interval (22.6 vs 31.0; P < 0.001), and area under the curve >10 mmol/L (0.18 vs 0.52 mmol/L per h; P < 0.001) were significantly lower. Hypoglycemia (glucose <3.8 mmol/L) was not observed during the mitiglinide/voglibose phase, but occurred 0.35 times/day in those taking glimepiride. Moreover, the mitiglinide/voglibose phase had higher premeal and lower post-meal glucose levels than the glimepiride phase.. Adding mitiglinide/voglibose to vildagliptin therapy results in more efficient postprandial glucose control and less hypoglycemia than adding glimepiride.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Isoindoles; Male; Middle Aged; Postprandial Period; Sulfonylurea Compounds; Treatment Outcome

Unlike in western countries, premixed insulin is widely used as the starter insulin in Asian patients instead of basal insulin. The use of basal-bolus therapy as an intensification regimen is not common in Asia despite poor glycaemic control after starting insulin therapy. An alternative insulin intensification regimen with a similar efficacy and safety profile to basal-bolus therapy, but of higher convenience, is urgently needed. The efficacy and safety of insulin lispro mix thrice-daily was compared with basal-bolus therapy in Asian patients with type 2 diabetes who were insufficiently controlled on twice-daily premixed insulin.. This open-label, randomised, active comparator-controlled, parallel-group trial was done at 24 centres in China, Taiwan, and South Korea. Patients with type 2 diabetes who were inadequately controlled on twice-daily premixed insulin were randomly assigned (1:1) to receive either insulin lispro mix (mix 50 before breakfast and lunch plus mix 25 before dinner) or basal-bolus therapy (insulin glargine at bedtime plus prandial insulin lispro thrice-daily) for 24 weeks. Randomisation was done by a computer-generated random sequence and was stratified by country or region and baseline HbA1c. Treatment assignments were masked from the study team assessing outcomes but not from investigators and patients. The primary outcome was change from baseline in HbA1c at week 24 in all randomly assigned patients who received at least one dose of study drug. Analysis was by modified intention to treat, with the per-protocol population used as a supportive analysis. This study is registered with ClinicalTrials.gov, number NCT01175811.. Between Feb 7, 2011, and Nov 7, 2012, 402 patients were enrolled (199 in the premix group, 203 in the basal-bolus group) and 399 were included in the primary analysis (197 in the premix group, 202 in the basal-bolus group). HbA1c change at week 24 was -1.1% for both treatment groups. The least squares mean difference between groups in HbA1c change from baseline was 0% (95% CI -0.1 to 0.2). Insulin lispro mix was non-inferior to basal-bolus therapy based on the prespecified margin of 0.4%. The frequency of adverse events, and the incidences and 30-day rates of nocturnal and overall hypoglycaemia were comparable between groups. No severe hypoglycaemia was reported.. A premixed insulin lispro regimen thrice-daily was non-inferior to basal-bolus therapy in terms of overall glycaemic control and thus could be an option for intensified insulin regimen in Asian patients with type 2 diabetes who are inadequately controlled with twice-daily premixed insulin.

Topics: Acarbose; Aged; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin Glargine; Insulin Lispro; Male; Metformin; Middle Aged; Republic of Korea; Taiwan; Treatment Outcome

We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2 mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24 weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p < 0.001) relative to αGI. At 24 weeks, the reduction was almost identical between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia.

Topics: 1-Deoxynojirimycin; Aged; alpha-Glucosidases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Gastrointestinal Agents; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Japan; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Sulfonylurea Compounds; Triazoles

Mitiglinide, a rapid- and short-acting insulinotropic sulfonylurea receptor ligand, exhibits hypoglycemic action unlike other sulfonylureas. The efficacy of the combination of mitiglinide and alpha-glucosidase inhibitors for diabetic patients on hemodialysis (HD) has not been prospectively evaluated; therefore, we evaluated the efficacy and safety of mitiglinide in these patients.. We performed an open-label randomized study with 36 type 2 diabetics with poor glycemic control on HD and receiving daily doses of voglibose (0.9 mg). The patients were randomly assigned to two groups: a combination-therapy group (mitiglinide group), mitiglinide initial dose 7.5 - 15 mg titrated to 30 mg daily and constant daily dose 0.9 mg of voglibose, and a monotherapy group (control group), constant daily dose 0.9 mg of voglibose alone. The efficacy of the treatment was determined by monitoring plasma glucose, hemoglobin A1c (Hb(A1c)), and glycated albumin (GA) levels and using homeostasis model assessment of insulin resistance (HOMA-IR). Safety and tolerance were determined by monitoring clinical and laboratory parameters.. The final dose of mitiglinide was 22.9 +/- 8.9 (mean +/- s.d.) mg (0.41 mg/kg) daily. Mitiglinide reduced fasting plasma glucose and GA levels after 4 weeks and Hb(A1c) levels after 8 weeks. Triglyceride levels and HOMA-IR values also decreased significantly after mitiglinide treatment. No significant changes in blood pressure levels or serious adverse effects such as hypoglycemia or liver impairment were observed.. This study suggests a combination therapy of mitiglinide and voglibose may have potential for the treatment of diabetics on HD. Due to the small sample size used, further studies should be performed, particularly to assess the safety of mitiglinide treatment.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Isoindoles; Male; Renal Dialysis; Treatment Outcome

An open-label prospective cross-over trial was performed to compare the efficacy and adverse effects of nateglinide with those of voglibose on Japanese early type 2 diabetes (who were oral hypoglycemic agent naïve and whose HbA(1C) levels were between 7.0 and 7.9% before treatment). Fourteen patients received 270 mg/day of nateglinide and 15 patients received 0.6 mg/day of voglibose. After 12 weeks of either therapy, the drugs were switched and treatment was continued for another 12 weeks. After 3-month treatment with each drug, HbA(1C) value decreased significantly (baseline HbA(1C) 7.24 +/- 0.42%, 6.70 +/- 0.47% with nateglinide: p<0.01, 6.93 +/- 0.62% with voglibose: p<0.05) but the difference in the effect between nateglinide and voglibose was not significant (p = 0.121). Symptoms related to hypoglycemia (e.g., increased appetite, palpitation, sweating, tremor) were scarcely observed with either voglibose or nateglinide treatments. Abdominal fullness/borborygmi was frequently reported, with variable severity, by patients on voglibose but this was absent or mild in those on nateglinide. After completion of both arms of the study, more patients favored nateglinide than voglibose. Our results suggest that nateglinide is an effective and safe drug in the treatment of early type 2 diabetes, similar to voglibose.

Topics: Aged; alpha-Glucosidases; Appetite; Body Weight; Cross-Over Studies; Cyclohexanes; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Gastrointestinal Tract; Glycated Hemoglobin; Humans; Hypoglycemia; Inositol; Lipids; Liver Function Tests; Male; Middle Aged; Nateglinide; Phenylalanine; Treatment Outcome

Nocturnal hypoglycemia is one of the serious complications of intensive insulin therapy in patients with insulin-dependent diabetes mellitus (IDDM; type 1 DM). We assessed the effect of voglibose (alpha-glucosidase inhibitor) administration before the evening meal on nocturnal hypoglycemia in IDDM patients with intensive insulin therapy. Ten IDDM patients received 0.3 mg voglibose just before the evening meal for 5 days. The diet and insulin regimen were not changed throughout the study. Nocturnal plasma glucose levels (10 PM, 3 AM, and 7 AM) were studied in these patients before and during voglibose administration. Blood glucose levels were measured at 3 AM before and during voglibose treatment. The mean plasma glucose level at 3 AM was 3.4+/-0.4 mmol/L before voglibose treatment and 7.3+/-1.0 mmol/L during treatment. Plasma glucose at 3 AM was elevated in 9 of 10 patients with voglibose. The decrease in plasma glucose from 10 PM to 3 AM was 6.5+/-0.8 mmol/L before voglibose administration but 3.2+/-0.9 mmol/L during treatment (P < .01). The hypoglycemia rate was 52% (17 of 33 nights) before voglibose administration but only 9.1% (3 of 33 nights) during treatment. We conclude that voglibose administration before the evening meal improves nocturnal hypoglycemia in IDDM patients with intensive insulin therapy.

Topics: Adolescent; Adult; Aged; Blood Glucose; Circadian Rhythm; Diabetes Mellitus, Type 1; Drug Administration Schedule; Eating; Enzyme Inhibitors; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin; Male; Middle Aged

Insulin injection, especially with insulin analogs, occasionally induces the production of insulin antibodies with high binding capacity and low affinity, similar to the insulin autoantibodies characteristic of insulin autoimmune syndrome (IAS). Production of these "IAS-like" insulin antibodies causes marked glycemic fluctuations with postprandial hyperglycemia and fasting hypoglycemia.. A 66-year-old man with a 27-year history of diabetes was admitted because of marked glycemic fluctuations. Human insulin treatment had been initiated at age 56, followed by multiple daily injections of insulin analogs 5 years later. After the initial year of insulin analog treatment, the patient began to experience frequent morning hypoglycemic attacks and day-time hyperglycemia. Marked hyperinsulinemia (4500 μU/mL) and high titers of insulin antibodies (80.4%) with high binding capacity and low affinity indicated that IAS-like insulin antibodies were causing severe glucose fluctuations. Altering insulin formulations (insulin aspart → regular human insulin→ insulin lispro) proved to be ineffective. After several therapeutic trials, cessation of exogenous insulin and addition of mitiglinide to liraglutide with voglibose finally attenuated glycemic fluctuations with increased postprandial insulin secretion. Continuous glucose monitoring revealed improvement of morning hypoglycemia and postprandial hyperglycemia with smaller mean amplitude of glycemic excursion. Therefore, compared to exogenously injected insulin, endogenously secreted insulin directly and rapidly acts on hepatocytes and suppresses postprandial glucose output.. Proper enhancement of postprandial endogenous insulin aimed at suppressing postprandial glucose output without stimulating excessive glucose uptake in the periphery is potentially useful for treating diabetes with insulin antibody-induced glycemic instability.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin; Insulin Antibodies; Insulin Secretion; Isoindoles; Liraglutide; Male; Postprandial Period; Treatment Outcome

Clinicians sometimes encounter difficulty in diagnosing hypoglycaemia. Here, we present a case report of a 53-year-old woman with recurrent nocturnal hypoglycaemia. A continuous glucose monitoring system (CGMS) revealed postprandial hyperglycaemia and subsequent hypoglycaemia, and an oral glucose tolerance test showed an impaired glycaemic and delayed hyperinsulinaemic pattern. On the basis of these clinical findings, we diagnosed her unexplained hypoglycaemia as reactive hypoglycaemia. CGMS showed a sharp contrast of diurnal variation in blood glucose levels including hypoglycaemia between before and after treatment with an alpha-glucosidase inhibitor, voglibose. Her hypoglycaemic attacks disappeared.

Topics: Blood Glucose; Circadian Rhythm; Diagnosis, Differential; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Middle Aged

We encountered a 62-year-old woman who experienced frequent episodes of hypoglycemia. She was diagnosed with postprandial reactive hypoglycemia according to the results of oral glucose and sucrose tolerance tests, having undergone an endocrinological examination and image inspection. The administration of low-dose voglibose, an alpha-glucosidase inhibitor (α-GI), improved the glucose fluctuations and inhibited hypoglycemic symptoms. Voglibose is also known to diminish oxidative stress and maintain endothelial function after hyperglycemia. An α-GI might effectively prevent hypoglycemic symptoms and endothelial dysfunction by suppressing oxidative stress in such cases.

Topics: Female; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Middle Aged; Oxidative Stress

Topics: Administration, Oral; Cardiovascular Diseases; Cyclohexanes; Diabetes Complications; Diabetes Mellitus; Drug Therapy, Combination; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemia; Hypoglycemic Agents; Indoles; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Isoindoles; Nateglinide; Phenylalanine; Risk Factors; Stimulation, Chemical; Sulfonylurea Compounds; Thiazolidinediones

Patients with type Ib glycogen storage disease (GSD Ib) are susceptible to hypoglycaemic episodes. To determine whether an amylase (alpha-glucosidase) inhibitor, voglibose, can be useful in the control of hypoglycaemia, we tried it in a 14-y-old male with GSD Ib. Oral administration of voglibose prolonged the duration of normoglycaemia and reduced the incidence of hypoglycaemia attacks. These findings indicate that voglibose may be useful for preventing hypoglycaemia in GSD Ib patients.

Topics: Adolescent; Blood Glucose; Glycogen Storage Disease Type I; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemia; Inositol; Male