Effect of liraglutide on lipids in patients with type 2 diabetes: a pilot study.

The mechanism for the cholesterol-lowering effect of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) remains unknown in patients with type 2 diabetes. We evaluated the effect of liraglutide on serum lipid profiles, including cholesterol synthesis and absorption markers, during daily clinical practice in Japanese patients with type 2 diabetes. We enrolled 38 patients with type 2 diabetes mellitus who were not treated with a GLP-1 RA (≥20 years of age, HbA1c ≥6.5%). Liraglutide, a GLP-1 RA, was administered subcutaneously once a day for three months to these patients. Blood samples and body weights were collected at 0, 1, and 3 months. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) at 1 month, and non-high-density lipoprotein cholesterol (non-HDL-C) and calculated TC at 1 and 3 months, were decreased, while the cholesterol synthesis and cholesterol absorption markers were unchanged by this treatment. In patients with LDL-C levels over 100 mg/dL, LDL-C, non-HDL-C, TC, and calculated TC levels were decreased significantly by the treatment at 1 and 3 months, and the cholesterol absorption marker, campesterol, was decreased at 3 months. The administration of liraglutide for 3 months decreased non-HDL-C and calculated TC significantly, while the cholesterol synthesis and absorption markers were not changed by this treatment.

Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).

BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones.

Elevation of postprandial plasma glucose is correlated with an increase in cardiovascular events, and alpha-glucosidase inhibitors (αGIs) are effective at reducing postprandial glucose levels. In Japan, the αGIs acarbose, voglibose, and miglitol have been available since 1993, 1994, and 2006, respectively. Dipeptidyl peptidase-4 (DPP-4) inhibitors are also effective at reducing postprandial glucose levels, and they have been available in Japan since 2009. A combination therapy of αGI, miglitol, and the DPP-4 inhibitor, sitagliptin, is more effective at decreasing postprandial glucose levels than monotherapy with either miglitol or sitagliptin. Moreover, the combination therapy of miglitol and sitagliptin is more effective at increasing postprandial active glucagon-like peptide-1 (GLP-1) levels than monotherapy. Peptide YY (PYY) has appetite-suppressing and gastric-emptying effects similar to GLP-1. In healthy individuals, miglitol increases the postprandial total PYY; however, combination therapy of miglitol and vildagliptin does not change postprandial total PYY levels. αGIs are typically prescribed to be taken just before a meal, which can result in decreased drug adherence. Different patterns of αGI intake were examined, and the results showed that miglitol or acarbose administration after a meal is effective. The effects of taking miglitol dissolved in water during a meal appeared to be similar to that of taking miglitol as a tablet just before a meal. The long-term effects of taking miglitol dissolved in water should be evaluated in future studies. αGIs may be effective even when they are not taken before a meal, and a more flexible administration may improve drug adherence.

Effects of miglitol, vildagliptin, or their combination on serum insulin and peptide YY levels and plasma glucose, cholecystokinin, ghrelin, and obestatin levels.

We previously reported that combination therapy with an α-glucosidase inhibitor (αGI) and a dipeptidyl peptidase-4 (DPP-4) inhibitor increased active glucagon-like peptide-1 (GLP-1) levels and decreased total glucose-dependent insulinotropic polypeptide (GIP) levels, compared with monotherapy, in non-diabetic men. However, the peptide YY (PYY), cholecystokinin (CCK), ghrelin, and obestatin levels in patients receiving a combination of αGIs and DPP-4 inhibitors have not been previously reported. We evaluated the effect of miglitol, vildagliptin, or their combination on these parameters. Miglitol and/or vildagliptin were administered according to four different intake schedules in eleven non-diabetic men (C: no drug, M: miglitol; V: vildagliptin, M+V: miglitol+vildagliptin). Blood samples were collected at 0, 30, 60, and 120 min after the start of breakfast. The plasma glucose, serum insulin, serum total PYY (PYY1-36 and PYY3-36), plasma CCK, plasma active ghrelin, and plasma obestatin levels were measured. The area under the curve (AUC) of the serum total PYY level in the M group was significantly greater than that in the C group, and the AUC of the serum total PYY level in the M+V group was significantly lower than that in the M group. The combination therapy did not change the AUC of the plasma CCK, plasma active ghrelin, plasma obestatin, and ghrelin/obestatin levels, compared with the control. The results of our study suggested that combination therapy with miglitol and vildagliptin had no effect on appetite regulation hormones, such as total PYY, CCK, active ghrelin, and obestatin, compared with the levels in the control group.

Mosapride citrate, a 5-HT4 receptor agonist, increased the plasma active and total glucagon-like peptide-1 levels in non-diabetic men.

Mosapride citrate, a selective agonist of the 5-hydroxytryptaine (5-HT)4 receptor, is typically used to treat heartburn, nausea, and vomiting associated with chronic gastritis or to prepare for a barium enema X-ray examination. Mosapride citrate reportedly improves insulin sensitivity in patients with type 2 diabetes. As mosapride citrate activates the motility of the gastrointestinal tract, we hypothesized that mosapride citrate affects incretin secretion. We examined the effect of the administration of mosapride citrate on the plasma glucose, serum insulin, plasma glucagon, and plasma incretin levels before breakfast and at 60, 120, and 180 min after breakfast in men with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) to exclude gastropathy. Mosapride citrate was administered according to two different intake schedules (C: control (no drug), M: mosapride citrate 20 mg) in each of the subject groups. The area under the curve (AUC) of the plasma glucose levels was smaller in the M group than in the C group. The time profiles for the serum insulin levels at 60 and 120 min after treatment with mosapride citrate tended to be higher, although the difference was not statistically significant. The AUCs of the plasma active and total glucagon-like peptide-1 (GLP-1) levels were significantly larger in the M group than in the C group. No significant difference in the AUC of the plasma glucose-dependent insulinotropic polypeptide (GIP) level was observed between the two groups. Our results suggest that mosapride citrate may have an antidiabetic effect by increasing GLP-1 secretion.

Comparison of plasma active glucagon-like peptide-1 (GLP-1) levels assayed with or without plasma extraction in non-diabetic men.

Recently, interference from cross-reacting peptides in plasma has been recognized as being responsible for inter-subject differences in active glucagon-like peptide-1 (GLP-1) values. An ethanol or solid-phase extraction step could reduce such interference. A working group of the Japan Diabetes Society now recommends the inclusion of an extraction step when measuring active GLP-1 values. We measured the active GLP-1 levels of 200 specimens derived from 10 subjects using both methods and compared the results. The active GLP-1 levels measured by extraction method for 169 specimens with values greater than 2.0 pM tended to be lower than those by direct method. However, the correlation between the GLP-1 levels measured by extraction and direct method was r=0.9225 (p < 0.0001). In one case, the active GLP-1 level obtained using the extraction method was significantly lower than that obtained using the direct method. Therefore, though there is a good correlation between the two methods, extraction is recommended for more accurate active GLP-1 measurements.

Effects of Canagliflozin on Hepatic Steatosis, Visceral Fat and Skeletal Muscle among Patients with Type 2 Diabetes and Non-alcoholic Fatty Liver Disease.

Objective We assessed the effect of canagliflozin, an sodium-glucose co-transporter type-2 inhibitor, on hepatic steatosis using three imaging modalities: magnetic resonance imaging (MRI), computed tomography, and transient elastography. We further determined factors associated with improving hepatic steatosis by canagliflozin among patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Methods We conducted a six-month prospective single-arm study between August 2015 and June 2017. The primary outcome was the change in hepatic steatosis assessed using the hepatic proton density fat fraction (PDFF) on MRI before and after treatment with canagliflozin. The secondary outcomes were changes in measures of glucose metabolism, including the hepatic glucose uptake on fluorodeoxyglucose-positron emission tomography, and the inflammation and volumes of visceral and subcutaneous adipose tissue and skeletal muscle. Patients Nine patients with type 2 diabetes and NAFLD completed this study. All participants received canagliflozin at a dose of 100 mg daily. Results Canagliflozin caused a significant reduction in hepatic PDFF from baseline [median 20.6% (interquartile range 11.7%, 29.8%)] after 6 months [10.6% (5.4%, 22.6%), p=0.008]. Canagliflozin also significantly reduced the body weight, glycated hemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hs-CRP), and volumes of adipose tissue and skeletal muscle (all p<0.05). The reduction in hepatic PDFF was not correlated with changes in the body weight, HOMA-IR, hs-CRP, or volume of adipose tissue and skeletal muscle from baseline after six months. Conclusion Among patients with type 2 diabetes and NAFLD, canagliflozin improved hepatic steatosis. The effect may be independent of reducing adiposity, insulin resistance, inflammation, and skeletal muscle volume.

Problems in diagnosing atypical Gitelman's syndrome presenting with normomagnesaemia.

OBJECTIVE: Gitelman's syndrome, recognized as a variant of Bartter's syndrome, is characterized by hypokalaemic metabolic alkalosis in combination with hypomagnesaemia and hypocalciuria. Overlapping biochemical features in Gitelman's syndrome and Bartter's syndrome has been observed. Here, we investigated the clinical, biochemical, and genetic characteristics of five, chronic, nonhypertensive and hypokalaemic Japanese patients. METHODS: Serum and urinary electrolytes, plasma renin activity and plasma aldosterone concentration were measured in five patients (four males and one female) with hypokalaemia. Renal clearance tests were performed and distal fractional chloride reabsorption calculated. Finally, mutational analysis of the thiazide-sensitive Na-Cl co-transporter gene was performed. RESULTS: Symptoms in patients varied from mild (muscle weakness and numbness) to severe (tetany and foot paralysis). All patients were normotensive or hypotensive, and all had hypokalaemia, hypocalciuria, and hyperreninaemic hyperaldosteronism. However, two male patients had normomagnesaemia, while the remainder was hypomagnesaemic. Renal clearance tests showed that the administration of furosemide decreased distal fractional chloride reabsorption, while thiazide ingestion failed to decrease it. Genetic analysis identified six thiazide-sensitive Na-Cl co-transporter gene mutations, including two novel ones. Therefore, on the basis of the confirmatory renal clearance tests and mutational analysis, a diagnosis of Gitelman's syndrome was made in these patients. CONCLUSIONS: Two of the five patients diagnosed with Gitelman's syndrome were normomagnesaemic, which is uncommon in this syndrome. Our study indicates that renal clearance tests and mutation analysis can play an important role in diagnosing Gitelman's syndrome more precisely.

Effects of miglitol, sitagliptin or their combination on plasma glucose, insulin and incretin levels in non-diabetic men.

alpha-glucosidase inhibitors (alphaGIs) increase active glucagon-like peptide-1 (GLP-1) and reduce the total glucosedependent insulinotropic polypeptide (GIP) levels, but their ability to prevent diabetes remains uncertain. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin, increase active GLP-1 and GIP levels and improve hyperglycemia in a glucose-dependent fashion. However, the effectiveness of their combination in subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) is uncertain. The present study evaluated the effect of miglitol, sitagliptin, and their combination on glucose, insulin and incretin levels in non-diabetic men. Miglitol and sitagliptin were administered according to four different intake schedules (C: no drug, M: miglitol; S: sitagliptin, M+S: miglitol and sitagliptin). The plasma glucose levels were significantly lower for M, S and M+S than for the control. The areas under the curve (AUCs) of the plasma active GLP-1 level in the M, S, and M+S groups were significantly greater than that in the control group. The AUC of the plasma active GLP-1 level was significantly greater for M+S group than for the M and S groups. The AUC of the plasma total GIP level was significantly smaller for M+S group than for the control and M and S groups. The results of our study suggest that miglitol, sitagliptin, or their combination contributes to the prevention of type 2 diabetes.

Effects of pre-meal versus post-meal administration of miglitol on plasma glucagon-like peptide-1 and glucosedependent insulinotropic polypeptide levels in healthy men.

We previously reported that the administration of miglitol after a meal was equally effective as administration before a meal. Since glucagon-like peptide-1 (GLP-1) reportedly promotes islet cell growth and inhibits apoptosis in animal models, an increase in GLP-1 secretion might also be beneficial for islet cell function and mass in humans. Miglitol reportedly enhances GLP-1 responses and reduces glucose-dependent insulinotropic polypeptide (GIP). However, whether the effect of miglitol on these incretins is comparable when miglitol is administered before or after a meal remains uncertain. Here, we compared the effects of the pre-meal versus post-meal administration of miglitol on the plasma active GLP-1 and total GIP levels in healthy men. Miglitol was administered according to three different intake schedules in each subject (control: no drug, intake 1: drug administered just before a meal [50 mg]; intake 2: drug administered at 30 min after the start of a meal [50 mg]). The area under the curve (AUC) of the plasma GLP-1 level for the intake 1 group was significantly greater than those of the control and intake 2 groups. The AUCs of the plasma GIP level for the intake 1 and 2 groups were significantly smaller than that of the control. The administration of miglitol just before a meal, rather than after a meal, is recommended in view of the up-regulation of GLP-1.

Correlations of fasting and postprandial blood glucose increments to the overall diurnal hyperglycemic status in type 2 diabetic patients: variations with levels of HbA1c.

Studies from overseas have indicated that postprandial glucose excursions are predominant in subjects with moderate hyperglycemia, while fasting hyperglycemia become the predominant abnormality with worsening of hyperglycemia; however, few studies have yet investigated the correlation between HbA1c and fasting and/or postprandial hyperglycemia in Japanese subjects. We investigated the correlation between fasting and postprandial hyperglycemia and the overall diabetic status, as assessed by measurement of HbA1c, in Japanese patients with type 2 diabetes. Blood glucose (BG) concentrations were determined in the fasting state (8:00 A.M.), during the postprandial phases (at 10:30 A.M., 2:30 P.M. and 8:30 P.M.) and during the postabsorptive periods (at 11:30 A.M. and 17:30 P.M.) in 66 patients with type 2 diabetes who were not being treated with prandial/premixed insulins or alpha-glucosidase inhibitors. The areas under the curve above the fasting BG concentrations (AUC1) and over 110 mg/dl (AUC2) were calculated for further evaluation of the correlations of the postprandial (AUC1) and fasting (AUC2 - AUC1) BG increments to the overall diurnal hyperglycemic status. Subjects were separated into two groups using the HbA1c cutoff value of 8%. The fasting BG was not correlated with the HbA1c in the group with a HbA1c values of less than 8% (r = 0.125, p = 0.473). On the other hand, fasting hyperglycemia was strongly correlated with the HbA1c level in the group with HbA1c values of over 8.0% (r = 0.406, p = 0.023). Furthermore, postprandial hyperglycemia was strongly correlated with the HbA1c in the group with HbA1c levels less than 8.0% (r = 0.524, p = 0.001). Thus, there existed a progressive shift in the contribution of fasting and postprandial hyperglycemia to the overall hyperglycemic status with progression from moderate to severe diabetes mellitus in Japanese type 2 diabetic patients.

Comparison of Lipid-Lowering Effects of Anagliptin and Miglitol in Patients With Type 2 Diabetes: A Randomized Trial.

BACKGROUND: Recently, we reported that the level of lathosterol, a cholesterol synthesis marker, was suppressed after 1 month of treatment with anagliptin, a dipeptidyl peptidase-4 inhibitor. In this study, we administered either anagliptin or miglitol, an alpha-glucosidase inhibitor, for 3 months in patients with type 2 diabetes and compared the lipid-lowering effects of anagliptin with those of miglitol. METHODS: This study was a 12-week, open-label, prospective, randomized, parallel-group comparison trial. Fifty-two patients with type 2 diabetes who aged 20 - 70 years with a low-density lipoprotein cholesterol (LDL-C) level of over 120 mg/dL, and with no history of treatment with antihyperlipidemic drugs were enrolled. Patients were randomly assigned to either the anagliptin group or miglitol group. The 100 mg of anagliptin was administered twice a day for the anagliptin group and 50 mg of miglitol was administered thrice a day for miglitol group. The changes in lipids, cholesterol synthesis, and absorption markers were evaluated after 12 weeks. RESULTS: Fifty-two participants were initially enrolled in the trial, and 47 of them completed the protocol. There was no significant difference in LDL-C, cholesterol synthesis, and the absorption markers between anagliptin and miglitol groups. CONCLUSIONS: Anagliptin and miglitol are similarly effective on lipid and glycemic control.

Comparative study of effectiveness of multiple-daily injections of insulin versus twice-daily injections of biphasic insulin in patients with type 2 diabetes.

To evaluate the efficacy of a multiple-daily injection regimen and a twice-daily injection regimen using biphasic insulin, we performed an observational study of 56 insulin-naïve patients with type 2 diabetes mellitus who began receiving insulin therapy while they were hospitalized. The subjects were divided into two groups: a multiple-daily injection group (n = 33), and a twice-daily injection group (n = 23). At baseline, the demographic and clinical characteristics were comparable between the two groups. The HbA1c levels were 10.0 +/- 1.6% and 9.5 +/- 2.2% (p = 0.36), respectively. At 12 weeks, the HbA1c levels decreased equally in the two groups (7.2 +/- 1.8% in the multiple-daily injection group and 7.3 +/- 1.6%, p = 0.80 in the twice-daily injection group). The baseline HbA1c, the duration of diabetes, and the endogenous insulin secretory capacity did not affect the change in HbA1c in either group. These results suggest that twice-daily insulin regimen using biphasic insulin is as effective and beneficial as multiple-daily injection regimen for the treatment in type 2 diabetic patients with very poor glycemic control and that in order to achieve the targeted glycemic goal, insulin therapy should be initiated at an early stage.

A novel initial codon mutation of the thiazide-sensitive Na-Cl cotransporter gene in a Japanese patient with Gitelman's syndrome.

We here report a novel mutation of the thiazide-sensitive Na-Cl cotransporter (TSC) (SLC12A3) gene in a Japanese patient with Gitelman's syndrome (GS). GS is characterized by a renal disorder and is associated with hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria arising from the defective tubular reabsorption of magnesium and potassium. This disease is reportedly caused by mutations in the TSC gene. A 52-year-old man was referred to our hospital because of sleeplessness and tinnitus. He exhibited hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and hyperreninemic hyperaldosteronism. A renal clearance study revealed that the administration of furosemide decreased chloride reabsorption; however, the ingestion of thiazide failed to decrease chloride reabsorption. A diagnosis of GS was made based on the clinical features, laboratory data and renal function test results. Sequencing of the patient's genomic DNA revealed an A to T transition at the initial codon of exon 1 of the TSC gene (c1A>T). Knowledge of this novel mutation may be helpful for understanding the pathophysiology of GS and the function of TSC as well as for providing genetic counseling.

Effect of Dehydroepiandrosterone (DHEA) on Diabetes Mellitus and Obesity.

Type 2 diabetes is a metabolic disorder that is characterized by an impaired capacity to secrete insulin, insulin resistance, or both. Dehydroepiandrosterone (DHEA), a steroid hormone produced by the adrenal cortex, has been reported to have beneficial effects on diabetes mellitus and obesity in animal models. DHEA and DHEA-sulfate (DHEA-S) have been reported to increase not only insulin secretion of the pancreas but also insulin sensitivity of the liver, adipose tissue, and muscle. We investigated the effects of DHEA on glucose metabolism in animal models and reported decrease of liver gluconeogenesis. Recently, we reported the effect of DHEA on the liver and muscle by using insulin-stimulated insulin receptor substrate 1 and 2 (IRS1 and IRS2)-deficient mice. DHEA increased Akt phosphorylation in the liver of C57BL6 IRS1- and IRS2-deficient mice fed with a high-fat diet (HFD), which suggests that the increase in DHEA-induced Akt signaling is sufficient in the presence of IRS1 or IRS2. In addition, other studies have also reported the effect of DHEA on diabetes mellitus in the liver, muscle, adipose tissue, and pancreatic ß-cell and its effect on obesity in animal models. A meta-analysis in elderly men and women has found that DHEA supplementation has no effects on blood glucose levels. However, DHEA supplementation to patients with type 2 diabetes has not been fully elucidated. Therefore, further studies are needed to provide greater insight into the effect of DHEA on diabetes and obesity in animal and human models.

A Randomized Controlled Trial of a Mini Low-Carbohydrate Diet and an Energy-Controlled Diet Among Japanese Patients With Type 2 Diabetes.

BACKGROUND: Low-carbohydrate diets have been shown to effectively improve the metabolic status of patients with type 2 diabetes mellitus. However, patients may find it challenging to maintain a strict low-carbohydrate diet. The objective of this study was to determine if a one-meal, low-carbohydrate diet is as effective in improving metabolic status as a conventional, energy-restricted diet among patients with type 2 diabetes mellitus. METHODS: In this 12-week randomized controlled study, the primary endpoint was differences in the changes of plasma glycosylated hemoglobin (HbA1c) levels between the two experimental groups. Since the two groups had differences in body weight, body mass index, and waist circumference, propensity score matching was used to assess HbA1c outcomes via cohort pairs according to age, sex, body weight, HbA1c level, and waist circumference. RESULTS: There were no differences in the changes in HbA1c between the two groups (P = 0.95). In addition, there were no differences in the changes in glycated albumin, 1,5-anhydroglucitol, lipid profile, body weight, waist circumference, and fat mass between the two groups. The mini low-carbohydrate diet group had an increased protein intake (P = 0.0085), as compared with the control group. However, neither group showed changes in their Diabetes Treatment Satisfaction Questionnaire score. CONCLUSION: Either diet would be effective for improving the metabolic status of this study population.

Correction to: A Randomized Controlled Trial of a Mini Low-Carbohydrate Diet and an Energy-Controlled Diet Among Japanese Patients With Type 2 Diabetes.

[This corrects the article DOI: 10.14740/jocmr3281w.].

Administration of miglitol until 30 min after the start of a meal is effective in type 2 diabetic patients.

Miglitol, a pseudomonosaccharide alpha-glucosidase inhibitor (alphaGI), was more effective at reducing blood glucose levels at 30 and 60 min after a meal than voglibose. Speculating that miglitol administered even after the start of a meal may be effective, we evaluated the timing of administration of miglitol on the plasma glucose and serum insulin levels in 13 type 2 diabetic patients. Miglitol was administered in four different intake manners in each patient (control: no miglitol; intake 1: just before breakfast; intake 2: 15 min after the beginning of breakfast; intake 3: 30 min after the beginning of breakfast). The area under the curve (AUC) of plasma glucose was significantly decreased under all the intake conditions, as compared with the AUC in the control. The AUC of serum insulin tended to be lower in all the three groups than in the control, although the differences were not statistically significant. Thus, miglitol administered anytime within 30 min after the start of a meal is effective for glycemic control. These results suggest that if patients miss taking miglitol at the beginning of a meal, they can still take the drug until 30 min after starting their meal.

Divided-dose administration of miglitol just before and 15 minutes after the start of a meal smoothes postprandial plasma glucose excursions and serum insulin responses in healthy men.

We recently demonstrated that administration of miglitol at 15 min after the start of a meal decreased the area under the curve (AUC) of plasma glucose, similar to the observation following its administration just before a meal. This finding prompted us to examine whether a divided-dose regimen of miglitol might attenuate postprandial glucose excursions even more effectively. We, therefore, examined several schedules of miglitol administration in 15 healthy men. Miglitol was administered by four different schedules in each subject (control: no miglitol, intake 1: drug administered just before a meal (50 mg); intake 2: drug administered at 15 min after the start of a meal (50 mg); intake 3: drug administered in two divided doses: just before a meal (25 mg) and at 15 min after the start of a meal (25 mg). The AUC of glucose excursions, defined as increment above the fasting glucose level, (AUC(0-180 min) of glucose excursions) was significantly reduced as compared with that in the control condition after miglitol administration by intake schedule 3, while this parameter showed a tendency towards decrease after the drug administration by intake schedules 1 and 2. The AUC(0-180 min) of the serum insulin level was also significantly decreased for all the intake schedules of miglitol, as compared with that in the control condition. Thus, administration of miglitol in two divided doses appeared to be the most suitable for obtaining effective regulation of postprandial glucose excursions in healthy men. This result may suggest that the divided-dose administration regimen may also be effective in diabetic patients.

Effect of Switching From an Anti-Diabetic Loose Dose Combination to a Fixed Dose Combination Regimen at Equivalent Dosage for 6 Months on Glycemic Control in Japanese Patients With Type 2 Diabetes: A Pilot Study.

BACKGROUND: Patients with type 2 diabetes mellitus often take multiple anti-diabetic drugs for a long period. Fixed dose combination (FDC) therapy is expected to improve drug adherence for patients with diabetes. The effect of switching from a loose dose combination (LDC) regimen to an FDC regimen at equivalent dosage on glycemic control has not been evaluated fully. Therefore, we investigated the effect of switching from LDC to FDC at equivalent dosage for 6 months on glycemic control in Japanese patients with type 2 diabetes. METHODS: Thirty-eight Japanese patients with type 2 diabetes who were taking anti-diabetic drugs including pioglitazone + metformin, pioglitazone + alogliptin, or pioglitazone + glimepiride were enrolled. These drugs were switched to an FDC of Metact®, Liobel® or Sonias®, respectively, at equivalent dosage. Other anti-diabetic drugs and units of insulin were not changed during the study if possible. HbA1c and body weight were measured 0, 2, 4 and 6 months after switching from an LDC to FDC. We also conducted a questionnaire survey 2 months after the start of the FDC regimen. RESULTS: HbA1c levels at 2, 4, and 6 months were not significantly changed compared with prior to switching from an LDC to FDC regimen. Moreover, 74.2% of patients considered decreasing the number of drugs to be "very good" or "good". CONCLUSION: HbA1c levels did not differ between patients receiving LDC and FDC therapy at equivalent dosage in this study.