nateglinide and Hyperglycemia

It has been hypothesized that reducing postprandial glucose spikes would result both in improved overall glycemic control and long-term (especially cardiovascular) outcomes in patients with type 2 diabetes. Nateglinide, a short-acting insulin secretagogue of the meglitinide class of antidiabetic agents, has been marketed for the past decade specifically to address the diminished postprandial insulin secretion. It is thus timely to review our experience with this agent.. This review summarizes findings from the key preclinical and pivotal clinical research studies that eventually led to drug approval. The literature search involved both original experimental studies and subsequent comprehensive reviews of the subject. The search included the databases (in English language) in the PubMed (maintained by the US Library of Medicine) domain as well as review of the articles in the author's files spanning the years 1995 - 2011.. The author's subjective feelings about our understanding of the importance of controlling postprandial glucose excursions and what, if any, effect nateglinide has had in that respect since its introduction are given. Despite promising animal and human research data, no evidence has accumulated to date to suggest that addressing postprandial hyperglycemia with nateglinide (or any other antidiabetic medication for that matter) leads to improved outcomes in patients with type 2 diabetes mellitus.

Topics: Animals; Blood Glucose; Clinical Trials, Phase II as Topic; Cyclohexanes; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Nateglinide; Phenylalanine; Randomized Controlled Trials as Topic

Diabetic macroangiopathy has already developed before diagnosis of diabetes mellitus. Postprandial hyperglycemia has been known as a risk factor for diabetic macroangiopathy and may be more powerful than fasting hyperglycemia. To intervene in hyperglycemia, insulin secretagogues, glinides which selectively stimulate early meal-induced insulin secretion and improve postprandial hyperglycemia, and sulfonylureas which enhance total daily insulin secretion and improve fasting hyperglycemia, have been prescribed as major oral antidiabetic agents. Few evidences that amelioration of glycemic control with insulin secretagogues lower the risk of cardiovascular diseases have been reported. But current studies have shown that intervention in postprandial hyperglycemia with drugs including glinides decreased thickness of carotid IMT as a surrogate marker of atherosclerosis. Results from on-going large scale intervention study with glinides may clarify whether amelioration of hyperglycemia lower the risk of atherosclerotic events.

Topics: Arteriosclerosis; Cardiovascular Diseases; Cyclohexanes; Diabetic Angiopathies; Glucose Intolerance; Hyperglycemia; Hypoglycemic Agents; Indoles; Insulin; Insulin Secretion; Isoindoles; Nateglinide; Phenylalanine; Postprandial Period; Risk Factors; Sulfonylurea Compounds

Topics: Acarbose; Cyclohexanes; Fasting; Glucose Intolerance; Glycation End Products, Advanced; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Life Style; Myocardial Ischemia; Nateglinide; Phenylalanine; Pioglitazone; Postprandial Period; Protein Kinase C; Thiazolidinediones

Topics: Cardiovascular Diseases; Clinical Trials as Topic; Cyclohexanes; Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Nateglinide; Obesity; Phenylalanine; Postprandial Period; Risk Factors

The mechanisms by which postprandial hyperglycemia is elicited were discussed through therapies of type 2 diabetes using "glinides". It has been believed that the earliest determinant of progression to type 2 diabetes is a loss of early insulin secretion, a defect which results in postprandial hyperglycemia and is often believed to reflect insulin resistance. To prove that, we improved insulin secretion pattern without increase of total amount of insulin secretion using glinide and assessed glucose response. Glinide which selectively enhances early meal-induced insulin secretion improved postprandial hyperglycemia, could provide a valuable treatment option in the prevention and treatment of type 2 diabetes.

Topics: Cyclohexanes; Diabetes Mellitus, Type 2; Eating; Humans; Hyperglycemia; Hypoglycemic Agents; Indoles; Insulin; Insulin Secretion; Isoindoles; Nateglinide; Phenylalanine

Several epidemiological studies have shown an association between postprandial hyperglycemia and mortality from cardiovascular disease. Postprandial hyperglycemia is frequently associated with visceral obesity which plays a key role in metabolic abnormalities such as dyslipidemia and hypertension. Inhibitors of alpha-glucosidase and nateglinide have beneficial effects on the metabolic syndrome associated with visceral obesity. Voglibose in combination with diet therapy reduces visceral fat deposition and ameliorates insulin resistance. Acarbose slightly reduces blood pressure of hypertensive diabetic patients. Nateglinide, a rapidly acting insulin secretagogue, lowers postprandial glucose levels without significant body weight gain. These drugs may protect pancreatic beta-cells from postprandial glucose toxicity and prevent the progression of diabetes.

Topics: Acarbose; Cyclohexanes; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Inositol; Insulin Resistance; Nateglinide; Obesity; Phenylalanine; Postprandial Period

Patients with type 2 diabetes mellitus are associated with insulin resistance and/or impaired insulin secretion. Previous observations indicate that Japanese patients with type 2 diabetes tend to have impaired insulin response after glycemic load more often than Caucasian counterparts. Recently it has been reported that hyperglycemia after glucose load is itself a risk factor for the development of cardiovascular complications in the absence of elevated fasting plasma glucose. Recent observations on the association of post-challenge or post-prandial hyperglycemia with cardiovascular events suggest that lowering post-prandial plasma glucose may protect patients from developing cardiovascular diseases. Results of STOP-NIDDM trial suggest that nateglinide, which attenuates post-prandial glycemic surge in type 2 diabetes, may also be helpful for the protection against cardiovascular events. Nateglinide exerts its effects shortly after its administration and the effects continue for only about 3 hours. The patients receiving this agent rarely gain weight and develop hypoglycemia. This agent exerts hypoglycemic effects additively with alpha-gulucosidase inhibitors or metformin.

Topics: Cardiovascular Diseases; Cyclohexanes; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemic Agents; Indoles; Insulin; Insulin Resistance; Insulin Secretion; Isoindoles; Metformin; Nateglinide; Phenylalanine; Postprandial Period; Stimulation, Chemical

Existing oral insulin secretagogues, sulphonylureas, are associated with hyperinsulinaemia, risk of hypoglycaemia and weight gain. Furthermore, they are not able to offer durable glycaemic control in patents with type 2 diabetes and are associated with progressive decline of beta-cell function. New insulin secretagogues offer an exciting opportunity. Repaglinide, the first prandial glucose regulator, now has convincing data that, compared to sulphonylurea use, it has a lower risk of hypoglycaemia. When used in a flexible dosing regime in a large cohort of patients, it is associated with better glycaemic control, a reduction in HbA1c, weight loss and improved quality of life compared to sulphonylureas. Early data shows the possibility of an effective combination with night time isophane insulin with significant falls in HbA1c and lower doses of insulin required. Nateglinide is an amino acid derivative. It again acts directly on the pancreatic beta-cell. Because of its very short duration of action, and the fact that it appears to secrete insulin in a glucose-dependent manner, it appears to secrete insulin in the closest way to that seen in a person without diabetes. Early data, both in monotherapy and in combination with metformin, show that it is an effective agent in terms of lowering HbA1c, has a low risk of hypoglycaemia and potentially less risk of significant weight gain. These characteristics mean that it may be the ideal agent to be used very early in the disease process, or even in subjects with impaired glucose tolerance, in whom early-phase insulin response is already lost. However these concepts, at the present time, are unproven.

Topics: Carbamates; Cyclohexanes; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hyperinsulinism; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Nateglinide; Phenylalanine; Piperidines; Postprandial Period; Sulfonylurea Compounds; United Kingdom

The United Kingdom Prospective Diabetes Study has shown that tight glycaemic control significantly reduces microvascular complications in Type 2 diabetes, but the effects on macrovascular complications were less impressive and did not reach statistical significance. Epidemiological studies have shown that post-prandial hyperglycaemia, rather than fasting hyperglycaemia, is more closely related to cardiovascular complications. It is, therefore, possible that previous studies may have overlooked the possible benefits of tight control of post-prandial hyperglycaemia as an important factor in reducing the cardiovascular mortality. Nateglinide is a novel D-phenylalanine derivative that inhibits ATP-sensitive K+ channels in pancreatic beta-cells in the presence of glucose and thereby restores first phase insulin response in patients with Type 2 diabetes. This helps in reducing post-prandial glucose excursion. Combination studies with metformin have shown it to be effective in controlling hyperglycaemia. While metformin reduces the basal plasma glucose, nateglinide helps in controlling post-prandial peaks. Nateglinide provides a new therapeutic option for treating Type 2 diabetes by specifically targeting post-prandial hyperglycaemia.

Topics: Animals; Clinical Trials as Topic; Cyclohexanes; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Guidelines as Topic; Humans; Hyperglycemia; Hypoglycemic Agents; Metformin; Microcirculation; Molecular Structure; Nateglinide; Phenylalanine; Postprandial Period

Studies have shown that repeated post-prandial hyperglycemia may play an important role in the development of atherosclerosis by suppressing endothelial function. α-Glucosidase inhibitors (α-GIs), which reduce post-prandial hyperglycemia without stimulating insulin secretion, significantly reduce the risk of coronary artery disease (CAD), whereas glinides, which improve post-prandial hyperglycemia through post-prandial insulin secretion, do not appear to affect CAD.. A total of 104 diabetic patients with CAD were randomly divided into 2 groups: those treated with miglitol (M-group; n=52) and those treated with nateglinide (N-group; n=52). After 4 months' treatment, although hemoglobin A1c and 1,5-anhydroglucitol were significantly improved in both groups, only the M-group had significant reductions in insulin resistance index and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C; a beneficial index for assessing the presence of small dense low-density lipoprotein, and a marker of atherogenic dyslipidemia). Furthermore, only the M-group had improvement in percentage flow-mediated dilatation (%FMD) and reactive oxygen metabolites. In the M-group, multiple regression analysis showed that improvement in TG/HDL-C, in addition to 1,5-anhydroglucitol, was an independent predictor of improvement in %FMD.. The ameliorating effect of α-GI on post-prandial hyperglycemia without stimulating insulin secretion may improve atherogenic dyslipidemia by reducing insulin resistance. These effects are associated with its beneficial impact on oxidative stress, consequently leading to an improvement in endothelial dysfunction.

Topics: 1-Deoxynojirimycin; Aged; Aged, 80 and over; Coronary Artery Disease; Cyclohexanes; Diabetic Angiopathies; Dyslipidemias; Endothelium, Vascular; Enzyme Inhibitors; Female; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Lipids; Male; Middle Aged; Nateglinide; Phenylalanine

Pasireotide, a multireceptor-targeted somatostatin analogue with efficacy in Cushing's disease and acromegaly, can affect glucose metabolism due to inhibition of insulin secretion and incretin hormone responses. A study was therefore conducted to evaluate different antihyperglycemic drugs in the management of pasireotide-associated hyperglycemia.. This was a 1-week, Phase I, open-label study. Healthy male volunteers were randomized to pasireotide 600 μg sc bid alone or co-administered with metformin 500 mg po bid, nateglinide 60 mg po tid, vildagliptin 50mg po bid, or liraglutide 0.6 mg sc qd. An oral glucose tolerance test (OGTT) was performed on days 1 and 7 to evaluate effects on serum insulin, plasma glucose and glucagon levels. Safety/tolerability and pharmacokinetic effects were also evaluated.. Ninety healthy male volunteers were enrolled (n=18 per arm). After 7 days of treatment, plasma glucose AUC post-OGTT increased by 69% with pasireotide alone. The effect was reduced by 13%, 29%, 45% and 72% with co-administration of metformin, nateglinide, vildagliptin and liraglutide, respectively. On day 7, compared with pasireotide alone, the decrease in serum insulin was attenuated with nateglinide, metformin, liraglutide and vildagliptin co-administration (levels were 3%, 6%, 34% and 71% higher, respectively). Minimal changes in plasma glucagon were observed. Adverse events were consistent with the safety profiles of the drugs used.. Vildagliptin and liraglutide were most effective in minimizing pasireotide-associated hyperglycemia in healthy volunteers.

Topics: Adamantane; Adolescent; Adult; Blood Glucose; Cyclohexanes; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Healthy Volunteers; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Liraglutide; Male; Maximum Tolerated Dose; Metformin; Middle Aged; Nateglinide; Nitriles; Phenylalanine; Prognosis; Pyrrolidines; Somatostatin; Vildagliptin; Young Adult

Postprandial hyperglycaemia in patients with Type 2 diabetes mellitus has been linked to the development of cardiovascular disease. This study compared the effects of mealtime (thrice-daily) nateglinide with once-daily glyburide on postprandial glucose levels in patients with Type 2 diabetes and postprandial hyperglycaemia.. Patients with Type 2 diabetes aged ≥ 21 years with 2-h postprandial glucose levels ≥ 11.1 mmol/l, HbA(1c) of 6.5-8.5% (48-69 mmol/mol) and BMI of 22-30 kg/m(2) were randomized to 6 weeks' double-blind treatment with nateglinide 120 mg three times daily prior to meals, or glyburide 5 mg once daily before breakfast. The primary endpoint was the baseline-adjusted change in plasma glucose from preprandial (fasting plasma glucose) to 2-h postprandial glucose levels (2-h postprandial glucose excursion) at 6 weeks.. Patients were randomized to nateglinide (n = 122) or glyburide (n = 110). The treatment groups were similar in terms of age, gender, BMI, fasting plasma glucose, 2-h postprandial glucose and HbA(1c). At endpoint, nateglinide recipients had significantly greater reductions than those receiving glyburide in both the 2-h (-2.4 vs. -1.6 mmol/l; P = 0.02) and 1-h (-1.7 vs. -0.9 mmol/l; P = 0.016) postprandial glucose excursions. Adverse events, most commonly symptomatic hypoglycaemia, were reported in 26% of recipients of glyburide and 22% of recipients of nateglinide. Episodes of suspected mild hypoglycaemia were reported in 24% of recipients of glyburide and 10% of recipients of nateglinide.. Nateglinide leads to greater reductions in postprandial glucose excursions and is associated with a lower risk of hypoglycaemia than glyburide in this selected population of patients with Type 2 diabetes.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Cyclohexanes; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Fasting; Female; Glyburide; Glycated Hemoglobin; Humans; Hyperglycemia; Middle Aged; Nateglinide; Phenylalanine; Postprandial Period

The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin-resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action. In the intervention group, postoral glucose-load (post-OGL) FMD delta values deteriorated when compared to pre-OGL values, most significantly at 3 h post-OGL, on the following days: on the first study day termed "Baseline day" (p=0.04); on both days after 3 months of nateglinide treatment [with nateglinide administered on study-day "acute+chronic" (p=0.01); and without nateglinide on study-day "Closing day", p=0.001]. Post-OGL changes in the control group were nonsignificant both at Baseline and on Closing day. After a single dose of nateglinide "Acute day", post-OGL FMD deterioration was abolished. There was an increment in post-OGL FMD delta values most significant at 2 h post-OGL (p=0.02). Insulin concentrations increased while glucose concentrations decreased on study-days with nateglinide when compared to study-days without (p=<0.001 for both insulin and glucose). Comparisons for insulin and glucose concentrations between days with nateglinide, and likewise between days without, showed no significant difference. Postglucose load endothelial dysfunction can be prevented by administration of nateglinide, however, after 3 months of nateglinide treatment, this effect is abolished. Chronically increased insulin secretion could counteract the initial beneficial effect of reduced glucose excursions. We found no relationship between postprandial hyperglycemia and post-OGL FMD.

Topics: Blood Glucose; Case-Control Studies; Cyclohexanes; Endothelium; Female; Glucose; Humans; Hyperglycemia; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Nateglinide; Phenylalanine; Postprandial Period; Risk Factors; Vasodilation

We studied the effects of nateglinide on serum adiponectin in 26 patients with type 2 diabetes mellitus. The changes in serum insulin at 30min significantly correlated with those in serum high-molecular weight adiponectin. Nateglinide may ameliorate hypoadiponectinemia as well as postprandial hyperglycemia in patients with type 2 diabetes mellitus.

Topics: Adiponectin; Aged; Cyclohexanes; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Molecular Weight; Nateglinide; Phenylalanine

Nateglinide, a rapid insulin secretagogue, is known to facilitate the early phase of insulin secretion and has been used for the treatment of type 2 diabetic patients with postprandial hyperglycemia. The aim of this study is to evaluate the effect of nateglinide on insulin resistance as well as insulin secretory defects in type 2 diabetic patients. Insulin secretion ability was evaluated by the hyperglycemic clamp test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test, using an artificial pancreas. The hyperglycemic clamp test showed that a 7-day treatment with nateglinide significantly increased insulin secretion in response to high glucose. Interestingly, although nateglinide is known to facilitate insulin secretion, daily urinary C-peptide excretion was decreased after nateglinide treatment. Moreover, in the euglycemic hyperinsulinemic clamp test, glucose infusion rate was significantly increased by nateglinide treatment, indicating that nateglinide functions to decrease insulin resistance. Nateglinide ameliorates insulin resistance as well as insulin secretory defects in type 2 diabetic patients.

Topics: Blood Glucose; Body Mass Index; Cyclohexanes; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Middle Aged; Nateglinide; Phenylalanine; Postprandial Period

To elucidate the role of early insulin response in post-prandial hyperlipidemia, we examined triglyceride (TG) and remnant-like particle triglyceride (RLP-TG) levels, using a meal tolerance test (MTT) with or without the administration of nateglinide (NAT). The MTTs were performed 2 d apart in 36 drug-naive patients with type 2 diabetes who had been hospitalized for glycemic control while receiving diet therapy. Before the second MTT, patients were treated with 90 mg NAT. Treatment with NAT was associated with a significant increase in insulin levels in the treated patients 1 h after the test meal, compared to levels in non-treatment. NAT treatment was also associated with a significant decrease in the level of free fatty acids 1 and 2 h after the meal, and with a significant decrease in plasma glucose levels 1, 2, and 4 h after the meal, compared to those in non-treatment. During the first MTT with NAT non-treatment, 13 patients showed serum TG levels of 200 mg/dL or greater when measured 2 h after the meal. In these 13 patients, NAT administration produced a significant decrease in TG levels 1, 2, and 6 h after the meal, as well as a significant reduction in RLP-TG levels 1 and 2 h after the meal. NAT administration was also associated with significant reductions in area under the curve (DeltaAUC) for TG and RLP-TG. These results suggest that, in a clinical setting, the early insulin response is closely associated with both postprandial glucose and postprandial lipid metabolism in Japanese patients with type 2 diabetes.

Topics: Blood Glucose; Cholesterol; Cyclohexanes; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Japan; Lipoproteins; Middle Aged; Nateglinide; Phenylalanine; Postprandial Period; Triglycerides

One hundred and sixteen Latin American type 2 diabetic patients previously only on a diet were enrolled in this multicenter, multinational, nonrandomized, noncontrolled study. Only 109 completed the study. After 8 weeks of treatment with 120 mg of nateglinide, administered prior to each meal, the postprandial (2 h) glucose concentration decreased to 85.11 +/- 5.65 mg/dl (p < 0.0001), and HbA(1c) values decreased to 1.06 +/- 0.10% (p < 0.0001). No response differences were detected in relation to age, gender, or ethnicity, but we did encounter a better response in recently diagnosed patients (

Topics: Blood Glucose; Cyclohexanes; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Latin America; Male; Middle Aged; Nateglinide; Phenylalanine; Postprandial Period; Treatment Outcome

This study was designed to compare the efficacy of three insulinotropic agents in the control of postprandial hyperglycemia in type 2 diabetes. Fifteen subjects with noninsulin-requiring type 2 diabetes were admitted to the General Clinical Research Center on four separate occasions. During the control study and following 7-10 d on each study medication, daylong glucose profiles were performed to investigate the effects of the assigned medication on postprandial hyperglycemia. During each admission, placebo or study medications were administered before three isocaloric meals as follows: immediate-release glipizide 30 min before breakfast and 30 min before supper, glipizide gastrointestinal therapeutic system (GITS) 30 min before breakfast, or nateglinide 120 mg 10 min before breakfast, before lunch, and before supper. Blood was drawn for analysis of glucose, insulin, and C-peptide at -0.05, 0, 0.25, 0.5, 1, 2, 3, and 4 h relative to each test meal. Immediate-release glipizide, nateglinide, or glipizide GITS administration resulted in significantly lower integrated daylong (glucose area under the curve) and peak glucose levels, compared with placebo. There were no significant differences in the daylong integrated glucose levels among the three study medications. The peak postbreakfast glucose level (but not glucose area under the curve) was lower with nateglinide, compared with either immediate-release glipizide or glipizide GITS. Postlunch and postdinner integrated glucose levels were significantly lower with immediate-release glipizide or glipizide GITS, compared with nateglinide. C-peptide levels were significantly higher with immediate-release glipizide, compared with glipizide GITS. Insulin levels did not differ among the three study medications. Once-daily glipizide GITS, twice-daily immediate-release glipizide, or three-times-a-day administration of nateglinide results in equivalent control of postmeal hyperglycemia in type 2 diabetes. The decision to prescribe one of these three insulinotropic agents should be based on factors such as the patient's ability to comply with complex dosing regimens, the need to control fasting hyperglycemia, the risk of interprandial hypoglycemia, and pharmacoeconomic considerations, rather than postprandial glucose-lowering efficacy.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cross-Over Studies; Cyclohexanes; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Female; Glipizide; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Nateglinide; Phenylalanine; Postprandial Period

To compare the effects of monotherapy using nateglinide and the thiazolidinedione troglitazone with initial combination of the two agents on glycated hemoglobin (HbA(1c)) in patients with type 2 diabetes inadequately controlled by diet alone.. This study consisted of a 28-week, double-blind, randomized, multicenter study that included a 4-week, single-blind, placebo, run-in period and a 24-week (shortened to 16 weeks), double-blind, active treatment period.. At the 16-week end point, nateglinide 120 mg, troglitazone 600 mg, and the combination of the agents achieved statistically significant decreases in HbA(1c) in comparison with placebo and a baseline HbA(1c) of 8.1-8.4% (P < 0.001). The reductions in HbA(1c) were similar in the nateglinide (0.6%) and troglitazone (0.8%) monotherapy groups. The reduction in HbA(1c) (1.7%) was greatest in the combination group; 79% of patients in the combination group achieved HbA(1c) levels of <7%. The combination group had a higher number of adverse events, primarily due to an increased incidence of mild hypoglycemia in this treatment group.. Nateglinide and troglitazone are equally effective in decreasing HbA(1c) levels. However, these reductions from baseline HbA(1c) values of >8% are not adequate to achieve HbA(1c) levels of <7%. In contrast, the combination of nateglinide and of a thiazolidinedione shows an additive effect that is highly effective in reducing HbA(1c) levels to the target of <7% in 66% of patients, from a baseline HbA(1c) that is just above 8%.

Topics: Adult; Aged; Cyclohexanes; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Middle Aged; Nateglinide; Phenylalanine; Thiazoles; Thiazolidinediones; Treatment Outcome

Nateglinide is a fast-acting insulin secretion agent that specifically targets postprandial hyperglycemia in patients with type 2 diabetes. The recent reduction in the diagnostic criteria for diabetes and improved understanding of the importance of early insulin secretion served as the rationale for this multicenter, double-blind, randomized, parallel-group, 24-wk study performed in 675 patients with type 2 diabetes but only moderately elevated fasting plasma glucose (FPG) (FPG = 7.0-8.3 mmol/liter) to assess the efficacy and safety of three fixed doses of nateglinide (30, 60, or 120 mg, with meals). A substudy of the effects on early insulin release and prandial glucose excursions following a standardized breakfast was performed in 127 subjects. Nateglinide was well tolerated and elicited a dose-dependent reduction of placebo-adjusted hemoglobin A(1c) (Delta = -0.26 to -0.39%) and FPG (Delta = -0.51 to -0.73 mmol/liter) accompanied by a dose-related increase in suspected hypoglycemic episodes. However, confirmed hypoglycemia occurred in only 5.3% of patients treated with the highest dose, compared with 1.2% in placebo-treated patients (P < 0.05). Nateglinide increased early insulin release and reduced prandial glucose excursions (P < 0.05 vs. placebo). In sum, nateglinide is a safe and effective therapeutic option for treatment of patients with mild to moderate fasting hyperglycemia.

Topics: Adult; Blood Glucose; Cyclohexanes; Diabetes Mellitus, Type 2; Double-Blind Method; Fasting; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Insulin Secretion; Male; Nateglinide; Phenylalanine; Racial Groups; Treatment Outcome

The insulin secretory pattern as a phenotype of type 2 diabetes is an impairment in the rapid, pulsatile secretion of insulin in response to a rise in blood glucose after meal-intake. The restoration of endogenous rapid insulin secretion after oral glucose load was established for the first time by using nateglinide, which is a newly developed insulin secretagogue, in obese patients with type 2 diabetes mellitus. It was clearly demonstrated that with nateglinide, serum insulin levels were quickly raised, and glycemic response curves were almost normalized with the same amount of insulin secretion during 180 min. Therefore, the lack of rapid, pulsatile secretion of insulin in response to glycemic rise after oral glucose load, rather than insulin resistance, is responsible for postprandial glycemic response in obese type 2 diabetes patients.

Topics: Adult; Cyclohexanes; Diabetes Mellitus, Type 2; Female; Glucose; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Nateglinide; Obesity; Phenylalanine; Postprandial Period

We herein report a case of hemichorea-hemiballism in an 85-year-old man diagnosed with diabetes at 76 years of age. After a one-year interruption in treatment, he was treated with a low-calorie diet, linagliptin, and nateglinide. Over 51 days, his HbA1c level decreased from 15.8% to 7.7%. After a prompt improvement in his hyperglycemia, he began experiencing involuntary movements in the right upper and lower extremities. T1-weighted magnetic resonance imaging showed a high signal intensity in the left lens nucleus. The patient was diagnosed with diabetic hemichorea-hemiballism and received haloperidol (1 mg/day) as treatment.

Topics: Chorea; Cyclohexanes; Diabetes Complications; Dyskinesias; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Linagliptin; Lower Extremity; Magnetic Resonance Imaging; Male; Middle Aged; Nateglinide; Phenylalanine

The glinides are the therapeutic agents for indications for type 2 diabetic patients with postprandial hyperglycemia. These are a class of drug which have a similar response as sulfonylureas but act for a shorter time and are prescribed to be taken by patients with type 2 diabetes within 5-10 min before eating. As the drugs act for a shorter period than sulfonylureas, the side effects of hypoglycemia and weight gain have a smaller likelihood. Combination with glinides and DPP4 inhibitors is a good choice for type 2 diabetic patients in early stage. Also combination therapy with glinides and alpha-glucosidase inhibitors shows a good profile of daily blood glucose level in these patients.

Topics: Cyclohexanes; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemic Agents; Isoindoles; Nateglinide; Phenylalanine

To reveal how often patients with rheumatoid arthritis (RA) or any of other connective tissue diseases (CTDs) who take prednisolone (PSL) manifest postprandial hyperglycemia, and to evaluate the effects of divided daily dose administration of PSL, and of acarbose and nateglinide, on RA patients.. The blood sugar (BS) levels of the patients were measured after meals. For in-patients who showed postprandial hyperglycemia, the daily dose of PSL was divided and nateglinide and/or acarbose were/was added if their BS levels did not improve sufficiently. The patients with BS levels that were well controlled for three months were compared with the patients with poorly controlled BS levels.. The BS levels of 78 patients, including 16 patients with diabetes mellitus (DM), were measured after meals, and 27 of them were newly diagnosed with DM. Five of 14 patients who took a steady dose of PSL showed high BS levels after lunch (over 200 mg/dl) without elevated HbA1c. The combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia significantly. The period from the start of PSL administration to intervention was significantly longer in patients with good control at three months than the corresponding period in those with poor control.. The prevalence of postprandial hyperglycemia was high in patients with RA/CTD taking PSL; accordingly, measurement of the BS level after each meal was valuable. Combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia.

Topics: Acarbose; Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Blood Glucose; Connective Tissue Diseases; Cyclohexanes; Diabetes Mellitus; Early Diagnosis; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Middle Aged; Nateglinide; Phenylalanine; Prednisolone; Treatment Outcome

Topics: Carbamates; Cyclohexanes; Glipizide; Humans; Hyperglycemia; Hyperlipidemias; Hypoglycemic Agents; Nateglinide; Phenylalanine; Piperidines; Postprandial Period; Sulfonylurea Compounds

Topics: Animals; Blood Glucose; Crystallization; Cyclohexanes; Female; Hyperglycemia; Hypoglycemic Agents; Male; Mice; Mice, Inbred ICR; Nateglinide; Phenylalanine; X-Ray Diffraction

The aim of this study was to clarify the role of an early insulin secretion in postprandial hyperglycaemia and hyperlipidaemia; a study using spontaneously type 2 diabetic Otsuka Long-Evans Tokushima Fatty rats with visceral obesity was performed to investigate the acute effect of nateglinide (NAT) vs. glibenclamide (GB) on increases in glucose after glucose loading and on increases in triglyceride (TG) after fat loading.. Fasting rats were given 50 mg/kg of NAT, 1 mg/kg of GB or 5% methyl cellulose (vehicle) as control and then immediately given oral glucose 1 g/kg.. An acute increase in insulin levels in portal blood peaked at 15 min in the NAT group, while insulin levels in the GB group continued to increase significantly after 60 min. Glucose levels in peripheral blood were significantly lower in the NAT group at 30 and 60 min and in the GB group at 120, 180 and 270 min after glucose loading, compared with those in the vehicle group. Subsequently, fasting rats were given NAT, GB or vehicle and then immediately given oral fat emulsion (soy oil 2 g/kg). An acute increase in insulin secretion was seen with NAT, peaking at 30 min, while TG, chylomicron and very low-density lipoprotein levels after fat loading were shown to be significantly lower with NAT than with vehicle. However, the continued insulin secretion observed with GB led to no significant decrease in TG levels after fat loading. In addition, lipoprotein lipase mRNA expression in adipose tissue increased significantly 120 min after NAT administration in comparison with baseline. This increase was not noted with GB administration.. Abnormalities in early insulin secretion are closely associated with the pathogenesis of various disease conditions that combine to characterize type 2 diabetes, suggesting that normalizing early insulin response in portal blood represents an important treatment not only for postprandial hyperglycaemia but also for postprandial hyperlipidaemia.

Topics: Adipose Tissue; Animals; Blood Glucose; Cyclohexanes; Diabetes Mellitus, Type 2; Dietary Fats; Gene Expression Regulation; Glyburide; Hyperglycemia; Hyperlipidemias; Hypoglycemic Agents; Insulin; Insulin Secretion; Lipoprotein Lipase; Male; Nateglinide; Phenylalanine; Postprandial Period; Rats; Rats, Inbred OLETF; Rats, Long-Evans; RNA, Messenger; Triglycerides

Topics: Cyclohexanes; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Metformin; Nateglinide; Phenylalanine; Postprandial Period

Topics: Advertising; Blood Glucose; Cyclohexanes; Diabetes Complications; Diabetes Mellitus; Disclosure; Drug Industry; Europe; Family Practice; Humans; Hyperglycemia; Hypoglycemic Agents; Meta-Analysis as Topic; Nateglinide; Phenylalanine; Prospective Studies; Risk; United Kingdom

This discussion contains excerpts from the satellite symposium, "Achieving Better Glycemic Control Through Management of Mealtime Glucose," presented at the American Association of Clinical Endocrinologists Tenth Annual Meeting and Clinical Congress in San Antonio, Texas, May 2, 2001.

Topics: Blood Glucose; Cyclohexanes; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Metformin; Nateglinide; Phenylalanine; Sulfonylurea Compounds