Α-glucosidase Inhibitor Miglitol Research Articles

Severe acute interstitial nephritis induced by α-glucosidase inhibitor miglitol in an elderly patient with type 2 diabetic nephropathy.

A 79-year-old male patient with type 2 diabetic nephropathy and hypertension was admitted to our hospital because of acute kidney injury with significantly elevated serum creatinine (8.12 mg/dL) and urinary β2-microglobulin (β2MG, 31,748 μg/L) levels. α-Glucosidase inhibitor (α-GI) miglitol, started two weeks prior to presentation, was discontinued because drug-induced acute interstitial nephritis (AIN) was suspected. Renal biopsy revealed AIN and diabetic nephropathy. The drug-induced lymphocyte stimulation test for miglitol was also positive. After the discontinuation of miglitol, the urinary β2MG levels decreased to the normal range. This case raises the possibility that α-GI miglitol can worsen the renal function in patients with underlying renal dysfunction.

Phloretin suppresses carbohydrate-induced GLP-1 secretion via inhibiting short chain fatty acid release from gut microbiome

We previously found that glucagon-like peptide 1 (GLP-1) secretion by co-administration of maltose plus an α-glucosidase inhibitor miglitol (maltose/miglitol) was suppressed by a GLUT2 inhibitor phloretin in mice. In addition, maltose/miglitol inhibited glucose-dependent insulinotropic polypeptide (GIP) secretion through a mechanism involving short chain fatty acids (SCFAs) produced by microbiome. However, it remains unknown whether phloretin suppresses GLP-1 secretion by modulating SCFAs. In this study, we examined the effect of phloretin on SCFA release from microbiome in vitro and in vivo. In Escherichia coli, acetate release into the medium was suppressed by phloretin, when cultured with maltose/miglitol. In mice, phloretin inhibited maltose/miglitol-induced SCFA increase in the portal vein. In addition, alpha methyl-d-glucose (αMDG), a poor substrate for GLUT2, significantly increased GLP-1 secretion when co-administered with phloridzin in mice, suggesting that GLUT2 is not essential for glucose/phloridzin-induced GLP-1 secretion. αMDG increased portal SCFA levels, thereby increasing GLP-1 secretion and suppressing GIP secretion in mice, suggesting that αMDG is metabolizable not for mammals, but for microbiota. In conclusion, phloretin is suggested to suppress maltose/miglitol-induced GLP-1 secretion via inhibiting SCFAs produced by microbiome.

Gut carbohydrate inhibits GIP secretion via a microbiota/SCFA/FFAR3 pathway.

Mechanisms of carbohydrate-induced secretion of the two incretins namely glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are considered to be mostly similar. However, we found that mice exhibit opposite secretory responses in response to co-administration of maltose plus an α-glucosidase inhibitor miglitol (maltose/miglitol), stimulatory for GLP-1, as reported previously, but inhibitory for GIP. Gut microbiota was shown to be involved in maltose/miglitol-induced GIP suppression, as the suppression was attenuated in antibiotics (Abs)-treated mice and abolished in germ-free mice. In addition, maltose/miglitol administration increased plasma levels of short-chain fatty acids (SCFAs), carbohydrate-derived metabolites, in the portal vein. GIP suppression by maltose/miglitol was not observed in mice lacking a SCFA receptor Ffar3, but it was normally seen in Ffar2-deficient mice. Similar to maltose/miglitol administration, co-administration of glucose plus a sodium glucose transporter inhibitor phloridzin (glucose/phloridzin) induced GIP suppression, which was again cancelled by Abs treatment. In conclusion, oral administration of carbohydrates with α-glucosidase inhibitors suppresses GIP secretion through a microbiota/SCFA/FFAR3 pathway.

Distinct action of the α-glucosidase inhibitor miglitol on SGLT3, enteroendocrine cells, and GLP1 secretion.

Oral ingestion of carbohydrate triggers glucagon-like peptide 1 (GLP1) secretion, but the molecular mechanism remains elusive. By measuring GLP1 concentrations in murine portal vein, we found that the ATP-sensitive K+ (KATP) channel is not essential for glucose-induced GLP1 secretion from enteroendocrine L cells, while the sodium-glucose co-transporter 1 (SGLT1) is required, at least in the early phase (5 min) of secretion. By contrast, co-administration of the α-glucosidase inhibitor (α-GI) miglitol plus maltose evoked late-phase secretion in a glucose transporter 2-dependent manner. We found that GLP1 secretion induced by miglitol plus maltose was significantly higher than that by another α-GI, acarbose, plus maltose, despite the fact that acarbose inhibits maltase more potently than miglitol. As miglitol activates SGLT3, we compared the effects of miglitol on GLP1 secretion with those of acarbose, which failed to depolarize the Xenopus laevis oocytes expressing human SGLT3. Oral administration of miglitol activated duodenal enterochromaffin (EC) cells as assessed by immunostaining of phosphorylated calcium–calmodulin kinase 2 (phospho-CaMK2). In contrast, acarbose activated much fewer enteroendocrine cells, having only modest phospho-CaMK2 immunoreactivity. Single administration of miglitol triggered no GLP1 secretion, and GLP1 secretion by miglitol plus maltose was significantly attenuated by atropine pretreatment, suggesting regulation via vagal nerve. Thus, while α-GIs generally delay carbohydrate absorption and potentiate GLP1 secretion, miglitol also activates duodenal EC cells, possibly via SGLT3, and potentiates GLP1 secretion through the parasympathetic nervous system.

Cotreatment with the α-glucosidase inhibitor miglitol and DPP-4 inhibitor sitagliptin improves glycemic control and reduces the expressions of CVD risk factors in type 2 diabetic Japanese patients

ObjectiveIn this study, we examined whether inhibition of postprandial hyperglycemia by combination therapy with two drugs for reducing postprandial hyperglycemia, i.e., α-glucosidase inhibitor miglitol and dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin, improves glycemic control and reduces the risk of cardiovascular disease (CVD) development. Materials/MethodsWe enrolled 32 type 2 diabetic Japanese patients with hemoglobin A1c (HbA1c) levels ranging from 6.9% to 10.5%, who had been treated for at least 2 months with 50mg miglitol (t.i.d.) or 50mg sitagliptin (q.d.). Following a monotherapy period with either miglitol (Group-M) or sitagliptin (Group-S) for 1 month, the patients were subjected to combination therapy with sitagliptin and miglitol for 3 months. Meal tolerance tests were performed at the end of the monotherapy and combination therapy. ResultsCombination therapy for 3 months after monotherapy reduced HbA1c (changes: Group-M: −1.3%±0.7%, P<0.001; Group-S: −0.6%±0.5%, P<0.001) and glycoalbumin levels and increased 1,5-anhydroglucitol concentrations in the blood. In the meal tolerance tests, circulating active glucagon-like peptide-1 levels were elevated in both groups, while active glucose-dependent insulinotropic polypeptide levels were reduced by combination therapy in the group with add-on miglitol therapy. The plasma protein concentrations of interleukin (IL)-8 and adhesion molecules (sE-selectin and sVCAM-1) were reduced by switching to the combination therapy, in particular with the add-on miglitol therapy. ConclusionsOur results suggest that combination therapy with miglitol and sitagliptin improves glycemic control and reduces the circulating protein concentrations of IL-8, sE-selectin, and sVCAM-1 in type 2 diabetic Japanese patients.

Anorexigenic Effects of Miglitol in Concert with the Alterations of Gut Hormone Secretion and Gastric Emptying in Healthy Subjects

Although the α-glucosidase inhibitor miglitol (MG) has been reported to have anorexigenic effects, the mechanism remains to be elucidated. The objective of this study was to explore the effects of MG on appetite in relation to concomitant changes in postprandial gut hormone levels. This randomized open-label crossover study included 20 healthy volunteers. The effects of 50 mg MG on glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin levels were assessed in conjunction with a simultaneous determination of appetite scores using visual analogue scales (VAS) over 3 h after the ingestion of a 592 kcal test cookie. Additionally, the gastric emptying rate (GER) was measured using breath ¹³CO₂ appearance in 10 subjects. 12 subjects were administered 50 mg MG thrice a day for 1 week, and alterations of the gut hormone levels and the VAS scores for appetite were evaluated. MG pre-administration resulted in a significant enhancement of GLP-1 and PYY responses induced by the cookie ingestion. Following MG administration, ghrelin level declined at 1 h, with a persistent suppression during the postprandial phase in contrast to the restoration to the basal level without MG. Furthermore, MG pre-administration suppressed appetite and maintained satiety evaluated using a VAS rating with concomitant inhibition of GER after cookie ingestion. One-week administration of MG did not influence either gut hormone levels before a meal or VAS rating during a whole day. These observations suggest that MG exerts an anorexigenic effects with concomitant alterations of gut hormone secretions and gastric emptying after meal ingestion.

Effect of the α-glucosidase inhibitor miglitol on the glucose profile in Japanese type 2 diabetic patients receiving multiple daily insulin injections

Strict postprandial glycemic control may have a preventive effect on atherogenesis in patients with type 2 diabetes. The α-glucosidase inhibitor (α-GI) miglitol is useful for controlling the early postprandial increase of glucose, but the combined effect of miglitol and multiple daily insulin injections (MDI) on glucose excursion has not been evaluated. First, we retrospectively compared the daily glucose profile, evaluated by self-monitoring of blood glucose (SMBG) at nine times on the day before discharge from hospital, between type 2 diabetic patients receiving MDI (n=81) or MDI plus miglitol at 150 mg daily (n=24). Second, we prospectively examined the effect of adding miglitol to MDI on the daily glucose profile (SMBG) in 19 other type 2 diabetic patients. Although the daily insulin dosage and the glucose level before meals did not differ between the two groups, the 1-h postprandial glucose level after each meal, 2-h glucose level after lunch and dinner, mean and standard deviation of glucose, and amplitude of glucose excursion were significantly lower or smaller in the MDI plus miglitol group than in the MDI group. All of these glucose parameters were significantly improved by adding miglitol to MDI in the prospective cohort of 19 patients. In conclusion, adding miglitol to MDI reduces postprandial glucose levels and attenuates daily glucose fluctuation in type 2 diabetic patients. This trial was registered with UMIN (no. UMIN000005383).

Treatment with the α-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes

Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, exhibit chronic and slowly progressive hyperglycemia with obesity. In this study, we examined whether dietary supplementation with the α-glucosidase inhibitor miglitol from the preonset stage improves glycemic control and reduces the gene expression of inflammatory cytokines in peripheral leukocytes. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 40 weeks from 5 weeks of age (preonset stage). We determined nonfasting blood glucose, blood 1,5-anhydroglucitol, and messenger RNA levels of inflammatory cytokines in peripheral leukocytes in these rats. Nonfasting blood glucose concentrations gradually increased in OLETF rats fed the control diet, with significant increases at weeks 28 and 40 compared with week 0. In contrast, nonfasting blood glucose levels did not increase in miglitol-treated rats during the experimental period. Miglitol-treated rats had lower nonfasting blood glucose levels and higher 1,5-anhydroglucitol levels, a marker for glucose fluctuations, at week 40 than control rats. The gene expression of inflammatory cytokines including interleukin-6, tumor necrosis factor-α, and interferon-γ in peripheral leukocytes gradually increased during the development of diabetes in control rats, but not in miglitol-treated rats. Our results suggest that dietary supplementation with miglitol from the preonset stage in OLETF rats improves glycemic control and reduces gene expression of cytokines related to inflammation in peripheral leukocytes.

Comparing the Efficacy of α-Glucosidase Inhibitors in Suppressing Postprandial Hyperglycemia Using Continuous Glucose Monitoring: A Pilot Study—The MAJOR Study

This study aimed to compare glucose variability in patients given the α-glucosidase inhibitors miglitol and acarbose using continuous glucose monitoring (CGM). Ten type 2 diabetes patients were hospitalized for 4 days, and their glucose levels were measured using CGM. Patients were given miglitol (50 mg) or acarbose (100 mg) before each meal on Day 2, and vice versa on Day 3, in a randomized crossover design. The patients had three identical test meals on Days 2 and 3. The CGM data were used to compare each parameter for glycemic variability after each of the three meals. No significant differences were observed between miglitol treatment or acarbose treatment in regard to the range of increase in glucose levels from baseline to peak, time to peak postprandial glucose levels from the preprandial period, and area under the curve for glycemic variability from the preprandial period to 3 h after each meal. However, the range of increase in glucose levels at 30 min (0.4 vs. 30.7 mg/dL, P < 0.0001) and 60 min (32.8 vs. 67.5 mg/dL, P <0.0001) after lunch and 30, 60, and 90 min after dinner (3.3 vs. 22.2 mg/dL, P = 0.0249; 36.6 vs. 67.5 mg/dL, P < 0.0001; and 60.5 vs. 81.6 mg/dL, P = 0.0073, respectively) was significantly smaller in miglitol treatment compared with acarbose treatment. In a pilot study with a crossover design in 10 type 2 diabetes patients, it was shown that although there was no significant difference in glucose variability with miglitol or acarbose after a fat-rich diet, glucose increases was significantly reduced with miglitol after a meal comprising typical Japanese diet 60-90 min postprandially.

The α-glucosidase inhibitor miglitol decreases glucose fluctuations and inflammatory cytokine gene expression in peripheral leukocytes of Japanese patients with type 2 diabetes mellitus

In this study, we examined the effects of switching from acarbose or voglibose to miglitol in type 2 diabetes mellitus patients for 3 months on gene expression of inflammatory cytokines/cytokine-like factors in peripheral leukocytes and on glucose fluctuations. We enrolled 47 Japanese patients with type 2 diabetes mellitus, aged 26 to 81 years, with hemoglobin A 1c levels ranging from 6.5% to 7.9% and who were treated with the highest approved dose of acarbose (100 mg per meal) or voglibose (0.3 mg per meal) in combination with insulin or sulfonylurea. Their prior α-glucosidase inhibitors were switched to a medium dose of miglitol (50 mg per meal), and the new treatments were maintained for 3 months. Forty-three patients completed the 3-month study and were analyzed. The switch to miglitol for 3 months did not affect hemoglobin A 1c, fasting glucose, triglycerides, total cholesterol, or C-reactive protein levels, or adverse events other than hypoglycemia symptoms. Hypoglycemia symptoms and glucose fluctuations were significantly improved by the switch. The expression of interleukin-1 β, tumor necrosis factor- α, and S100a4/6/9/10/11/12 genes in peripheral leukocytes, and the serum tumor necrosis factor- α protein levels were suppressed by switching to miglitol. Miglitol reduces glucose fluctuations and gene expression of inflammatory cytokines/cytokine-like factors in peripheral leukocytes of type 2 diabetes mellitus patients more than other α-glucosidase inhibitors and with fewer adverse effects.

Changes in α-glucosidase activities along the jejunal-ileal axis of normal rats by the α-glucosidase inhibitor miglitol

Miglitol, an α-glucosidase inhibitor that inhibits postprandial hyperglycemia by delaying carbohydrate digestion and absorption along the jejunal-ileal axis, has recently been approved for use in patients with type 2 diabetes mellitus. Miglitol treatment may lead to increased α-glucosidase activities toward the ileum because carbohydrate flow toward the ileum increases. However, it is not yet known if miglitol treatment alters the α-glucosidase activities along the jejunal-ileal axis. In this study, we examined the effects of miglitol supplementation for 3 or 7 days on α-glucosidase activities along the jejunal-ileal axis of Wistar rats. Supplementation with miglitol for 3 or 7 days in rats increased tissue weights of the lower jejunum and ileum, but did not alter tissue weights of the upper jejunum and cecum or the contents of the cecum. Furthermore, supplementation with miglitol for 7 days reduced the activities of isomaltase and maltase in the upper jejunum and increased the activities of sucrase, isomaltase, and maltase in the lower jejunum and ileum. These results suggest that the delay in carbohydrate digestion and absorption along the jejunal-ileal axis by miglitol supplementation in rats is associated with increased α-glucosidase activities toward the ileum.

The α-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic β-cells in OLETF rats

The Otsuka Long–Evans Tokushima Fatty (OLETF) rat, an animal model of type 2 diabetes, exhibits obesity, hyperglycemia and hyperlipidemia, with late onset of chronic and slowly progressive hyperinsulinemia. In this study, we examined effects of long-term dietary supplementation with the α-glucosidase inhibitor miglitol on the development of diabetes and the reduction of β-cells in the pancreas of OLETF rats. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 65 weeks from pre-onset stage (5 weeks old). The non-fasting blood glucose concentrations gradually increased in OLETF rats fed the control diet and, at week 64, were significantly higher than those in OLETF rats fed the miglitol diet and age-matched Long–Evans Tokushima Otsuka (LETO) rats, which are control, non-diabetic, non-obese rats of the same strain. Oral glucose tolerance tests revealed that OLETF rats fed the control diet showed pronounced impaired glucose tolerance, but those fed the miglitol diet did not. Furthermore, insulin concentrations after glucose-loading were significantly lower in OLETF rats fed the control diet than in those fed the miglitol diet. The islets of 65-week-old OLETF rats fed the control diet showed significant fibrosis and loss of β-cells, while those of age-matched control LETO rats had a normal appearance. Feeding OLETF rats a miglitol diet reduced fibrosis and the loss of β-cells. Our results suggest that dietary supplementation with miglitol from pre-onset stage in OLETF rats delays the onset and development of diabetes and preserves the insulin secretory function of pancreatic islets.

The α-glucosidase inhibitor miglitol decreases glucose fluctuations and gene expression of inflammatory cytokines induced by hyperglycemia in peripheral leukocytes

Objective Postprandial hyperglycemia is thought to cause inflammation in many tissues. In this study, we examined whether the gene expression of inflammatory cytokines/cytokine-like factors in peripheral leukocytes are altered by feeding streptozotocin-treated rats a diet containing an α-glucosidase inhibitor, miglitol. Methods Upregulated gene expression in peripheral leukocytes of streptozotocin-induced hyperglycemic rats was determined by microarray analysis. We examined whether gene expression was altered by supplementing the diet with miglitol. Results Microarray analysis revealed that gene expression of interleukin-1β and putative inflammatory cytokines, S100a4/6/8/9, was induced by streptozotocin treatment. Dietary supplementation with miglitol to the streptozotocin-induced hyperglycemic rats for 20 d not only increased plasma concentrations of a marker for glucose fluctuations, 1,5-anhydroglucitol, the concentration of which is decreased by sustained or postprandial elevated blood glucose levels, but also suppressed the induction of interleukin-1β and S100a4/6/8/9 genes by hyperglycemia. Conclusion These results suggest that miglitol inhibits the gene expression of inflammatory cytokines/cytokine-like factors in peripheral leukocytes by suppressing glucose fluctuations.

The α-glucosidase inhibitor miglitol suppresses postprandial hyperglycaemia and interleukin-1β and tumour necrosis factor-α gene expression in rat peripheral leucocytes induced by intermittent sucrose loading

Postprandial hyperglycaemia is thought to increase inflammation in leucocytes. In the present study, we examined whether sucrose loading in rats with moderate postprandial hyperglycaemia induces the expression of cytokines in peripheral leucocytes and whether these inductions are suppressed by inhibiting postprandial hyperglycaemia with the alpha-glucosidase inhibitor miglitol. One group of streptozotocin-treated rats and age-matched saline-treated rats were orally administered sucrose only, and another group of streptozotocin-treated rats was administered sucrose with miglitol, at a single daily dose for 4 d, under 4 h fasting conditions. Blood glucose levels at 0, 0.25, 0.5, 1, 2 and 3 h and cytokine mRNA in peripheral leucocytes at 0 and 3 h after sucrose loading on days 1 and 4 from the start of sucrose loading were determined. Streptozotocin-treated rats showed moderate postprandial hyperglycaemia (>2000 mg/l) at 0.25-1 h after sucrose loading on days 1 and 4. Postprandial hyperglycaemia was not observed in the miglitol-treated rats loaded with sucrose. Gene expression levels of IL-1beta and TNF-alpha were higher in the streptozotocin-treated rats at fasting on day 1 than in saline-treated rats. Fasting IL-1beta and TNF-alpha gene expression on day 1 were not only increased at 3 h on the same day of sucrose loading, but was also increased at the fasting period on day 4. These inductions on day 4 by intermittent sucrose administration were inhibited by miglitol. The present results suggest that miglitol decreases postprandial hyperglycaemia and intermittent sucrose-induced expression of the IL-1beta and TNF-alpha genes in rat peripheral leucocytes.

Miglitol increases the adiponectin level and decreases urinary albumin excretion in patients with type 2 diabetes mellitus

Postprandial hyperglycemia is associated with increased cardiovascular mortality; therefore, lowering postprandial hyperglycemia seems crucial in type 2 diabetes mellitus. We assessed the effect of 2 different postprandial glucose-lowering agents, the α-glucosidase inhibitor miglitol and the meglitinide analogue mitiglinide, on metabolic profile and atherosclerosis-related markers. Glucose levels, insulin levels, lipid profile, serum adiponectin, pulse wave velocity (PWV), and urinary albumin excretion rate (AER) were assessed before and after 3 months in 28 patients with type 2 diabetes mellitus randomly allocated to either miglitol 150 mg/d or mitiglinide 30 mg/d. Both agents improved postprandial glucose levels but exhibited different patterns of insulin levels. Body mass index (BMI) tended to decrease with miglitol ( P = .06), and homeostasis model assessment of insulin resistance and AER significantly decreased ( P < .05 and P < .001, respectively) with miglitol; these changes were not obtained with mitiglinide. Pulse wave velocity did not change. The 3-month changes in 1,5-anhydroglucitol levels were significantly more with miglitol than with mitiglinide ( P = .007). Adiponectin levels were significantly increased only with miglitol ( P < .01), and the 3-month changes were significantly more with miglitol than with mitiglinide ( P = .048). The significant increase in adiponectin by miglitol was inversely correlated with the ratio of the 60-minute change in blood glucose at 3 months divided by the change at baseline ( r = −0.59, P = .020), which was independent of the effect of age, sex, changes in hemoglobin A 1c and BMI, and the baseline concentration of adiponectin. The present comparative study indicated favorable effects of miglitol on BMI, homeostasis model assessment of insulin resistance, adiponectin, and AER, which are markers related to insulin resistance and atherosclerosis. Future studies are needed to elucidate the long-term effect.

Voglibose, an Anti-diabetic Drug, Reduces Myocardial Infarct Size and Improves Left Ventricular Function in Rabbits

Purpose: We previously reported that α-glucosidase inhibitors miglitol and acarbose reduce the myocardial infarct size. Therefore, we hypothesized that voglibose also has an effect to reduce the myocardial infarct size.

Detection of aromatic alpha-hydroxyketones with tetrazolium salts.

In principle there are two ways for the biocatalytic synthesis of α-hydroxyketones. Oxidoreductases may be used to convert diketones or diols into the respective α-hydroxyketones. This kind of reaction is exploited, e.g., in the industrial synthesis of the α-glucosidase inhibitor miglitol ([2R,3R,4R,5S]-1-[2-hydroxyethyl]-2-[hydroxymethyl]-3,4,5-piperidintriole) (). Alternatively, thiamine diphosphate dependent transketolases are capable of synthesizing α-hydroxyketones by catalyzing the transfer of activated glycolaldehyde (). In natural biosyntheses these enzymes are usually found in sugar metabolism. Another thiamine diphosphate-dependent enzyme is used for the industrial production of R-phenylacetylcarbinol ([1R]-1-hydroxy-1-phenyl-propan-2-one). R-phenylacetylcarbinol (R-PAC) is the first chiral intermediate in the production process of pseudoephedrine and ephedrine. Since 1921, it has been known that yeast (Saccharomyces cerevisiae) are able to catalyze the formation of R-PAC (,). The further synthetic steps from R-PAC to pseudoephedrine are carried out by classical chemical synthesis (). The actual enzyme in yeast catalyzing the synthesis of R-PAC is pyruvate decarboxylase (PDC; EC 4.1.1.1). In vivo this enzyme converts pyruvate to acetaldehyde. 2-α-Hydroxyethyl-thiamine diphosphate (“activated acetaldehyde”) is an intermediate of the catalytic cycle of PDC. Its α-carbanion reacts with several aldehydes in a nucleophilic attack to form the respective acyloins (). In this manner, benzaldehyde and pyruvic acid form R-PAC and CO2

The Efficacy and Safety of Miglitol Therapy Compared With Glibenclamide in Patients With NIDDM Inadequately Controlled by Diet Alone

To compare the therapeutic effects of the alpha-glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone. After a 4-week placebo run-in period, 201 patients in 18 centers in 4 countries were randomized in a double-blind manner to miglitol (50 mg t.i.d., followed by 100 mg t.i.d.), glibenclamide (3.5 mg q.d/b.i.d.), or placebo for 24 weeks. Efficacy criteria were changes from baseline of HbA1c, fasting and postprandial blood glucose and insulin levels, body weight, and serum triglycerides. Efficacy was assessed in 119 patients who completed the full protocol, and the results were similar to those obtained in 186 patients who fulfilled the validity criteria for analysis. Compared with placebo, mean baseline-adjusted HbA1c decreased by 0.75% (P = 0.0021) and 1.01% (P = 0.0001) in the miglitol and glibenclamide treatment groups, respectively. Blood glucose decreased slightly in the fasting state and considerably in the postprandial state in both treatment groups but not in the placebo group. Fasting insulin levels increased slightly (NS) in all treatment groups; however, postprandial insulin levels decreased with miglitol, while increasing markedly with glibenclamide (P = 0.0001 between all treatment groups). Gastrointestinal side effects (flatulence and diarrhea) occurred mostly in the miglitol-treated patients, while some glibenclamide-treated patients had symptoms suggestive of hypoglycemia. Miglitol monotherapy is effective and safe in NIDDM patients. Compared with glibenclamide, it reduced HbA1c less effectively and caused more gastrointestinal side effects. On the other hand, glibenclamide, unlike miglitol, tended to cause hypoglycemia, hyperinsulinemia, and weight gain, which are not desirable in patients with NIDDM.

Does Suppression of Postprandial Blood Glucose Excursions by the α-Glucosidase Inhibitor Miglitol Improve Insulin Sensitivity in Diet-Treated Type II Diabetic Patients?

Insulin sensitivity is impaired in patients with type II diabetes and is exacerbated by high mean blood glucose (BG). Potentially, large postprandial swings in BG could result in further decrements of insulin sensitivity. Because alpha-glucosidase inhibitors cause a marked reduction in the amplitude of BG changes, the aim of this study was to determine if such a BG-smoothing effect improves insulin sensitivity in well-controlled type II diabetic subjects treated with diet alone. Patients received either miglitol (BAY m 1099) (50 mg three times daily) or placebo for 8 weeks in a randomized double-blind parallel study. The miglitol (9 men, 2 women) and placebo (7 men, 3 women) groups were well matched (mean +/- SD) for age, weight, and blood glucose control (fasting BG, 6.4 +/- 1.0 vs. 6.9 +/- 1.6 mmol/l; HbA1, 7.7 +/- 1.0 vs. 7.9 +/- 0.4%; fructosamine, 0.99 +/- 0.08 vs. 1.07 +/- 0.17 mmol/l). The glucose metabolic clearance rate was calculated during the last 30 min of a 150 min glucose/insulin sensitivity test (glucose, 6 mg . kg-1 . min-1; insulin, 0.5 U . kg-1 . min-1). There was no significant improvement in metabolic clearance rate (0.21 +/- 0.27 vs. 0.16 +/- 0.35 l . kg-1 . min-1) for the miglitol- and placebo-treated groups, respectively. There were no statistically significant differences between miglitol and placebo for changes from baseline in BG (0.1 +/- 0.1 vs. -0.1 +/- 0.2 mmol/l), HbA1 (0.1 +/- 0.1 vs. 0.3 +/- 0.1%), and fructosamine (-0.06 +/- 0.02 vs. -0.03 +/- 0.02 mmol/l). Alpha-glucosidase-induced improvement in postprandial hyperglycemia does not result in increased insulin sensitivity.