AIM: To investigate the efficacy and safety of miglitol vs. placebo in type 2 diabetic outpatients insufficiently controlled (HbA1c between 7.5 and 10.5%) with diet and metformin. METHODS: Patients treated with diet and metformin (1500-2250 mg/day) were randomized to receive additional treatment with either miglitol or placebo for 32 weeks. The dosages were force-titrated: 4 weeks at 25 mg miglitol t.i.d., 12 weeks at 50 mg miglitol t.i.d., and 16 weeks at 100 mg miglitol t.i.d. or matching placebo. If the highest dosage could not be tolerated, patients could be down-titrated to 50 mg t.i.d. The primary efficacy criterion was the change in glycated haemoglobin (HbA1c). Secondary efficacy parameters included fasting and 1 h postprandial blood glucose, serum insulin, and fasting and 1 h postprandial triglyceride levels. Safety and tolerability were evaluated by the incidence of adverse events and changes in vital signs or routine biochemical and haematological parameters. RESULTS: One hundred and fifty-two patients were valid for the intent-to-treat (ITT) analysis. There was a significant decrease in HbA1c on adding miglitol to metformin compared to adding placebo (miglitol treatment effect, - 0.21%; placebo treatment effect, + 0.22%; p = 0.011). Postprandial blood glucose declined in both the miglitol/metformin and placebo/metformin groups with a statistically significant difference in favour of miglitol/metformin (end of treatment adjusted means 13.8 mmol/l for miglitol vs. 15.8 mmol/l for placebo, p = 0.0007). Adverse events (AEs) were reported by only 8% more patients in the miglitol/metformin group than placebo/metformin. No cases of hypoglycaemia were reported. CONCLUSIONS: Miglitol can safely and effectively be added to diet and metformin in patients whose type 2 diabetes is insufficiently controlled, and improves glycaemic control by significantly reducing HbA1c and postprandial blood glucose levels.

The efficacy of the new intestinal alpha-glucosidase inhibitor, miglitol, and glibenclamide were compared in a 6-month double-blind controlled protocol involving 100 non-insulin dependent diabetic patients under diet alone. HbA1c levels (initially between 7 and 11%) were reduced (p < 0.05): -0.78 +/- 0.21% after miglitol and -1.18 +/- 0.20% after glibenclamide. The difference between the two treatments was not significant, although glibenclamide appeared to be more active than miglitol at 8 (p = 0.002) and 16 weeks (p = 0.01) but not at 24 weeks. Fasting glycaemia decreased after miglitol (8.7 +/- 0.3 vs 9.6 +/- 0.3 mmol/l, p = 0.005) and after glibenclamide (8.0 +/- 0.3 vs 9.1 +/- 0.3, p = 0.007). After miglitol, a decrease was noted after breakfast (p < 0.001) and lunch (p < 0.001). The same was true for glibenclamide (p = 0.004 and p < 0.001 respectively). A significant reduction in glucose incremental area during a standard meal test was noted at the end of miglitol (p = 0.008) or glibenclamide treatment (p = 0.04). Subgroups of nonresponders to both treatments were identified (10/49 with miglitol, 9/47 with glibenclamide). Side effects were recorded in 10 patients treated with miglitol (flatulence and meteorism, diarrhoea, 1 discontinued therapy) and in 10 treated with glibenclamide (asthenia, sensation of hunger). This study indicates that miglitol is suitable for initial application in diet-resistant Type 2 diabetic patients, providing, a persistent effect and acceptable side effects.

OBJECTIVE: To investigate the efficacy and safety of miglitol in combination with metformin in improving glycemic control in outpatients in whom type 2 diabetes is insufficiently controlled by diet alone. RESEARCH DESIGN AND METHODS: In this multicenter, double-blind, placebo-controlled study, 324 patients with type 2 diabetes were randomized, after an 8-week placebo run-in period, to treatment with either placebo, miglitol alone, metformin alone, or miglitol plus metformin for 36 weeks. The miglitol was titrated to 100 mg three times a day and metformin was administered at 500 mg three times a day. The primary efficacy criterion was change in HbA(1c) from baseline to the end of treatment. Secondary parameters included changes in fasting and postprandial plasma glucose and insulin levels, serum triglyceride levels, and responder rate. RESULTS: A total of 318 patients were valid for intent-to-treat analysis. A reduction in mean placebo-subtracted HbA(1c) of -1.78% was observed with miglitol plus metformin combination therapy, which was significantly different from treatment with metformin alone (-1.25; P = 0.002). Miglitol plus metformin also resulted in better metabolic control than metformin alone for fasting plasma glucose (-44.8 vs. -20.4 mg/dl; P = 0.0025), 2-h postprandial glucose area under the curve (-59.0 vs. -18.0 mg/dl; P = 0.0001), and responder rate (70.6 vs. 45.52%; P = 0.0014). All therapies were well tolerated. CONCLUSIONS: In type 2 diabetic patients, miglitol in combination with metformin gives greater glycemic improvement than metformin monotherapy.

OBJECTIVE: The study compared the long-term efficacy and safety of miglitol to placebo in Type 2 diabetic outpatients inadequately controlled on combination therapy of diet, glibenclamide and metformin. METHODS: Type 2 diabetic patients (n = 154) receiving glibenclamide 7-20 mg/day and at least one 500-850 mg tablet metformin per day were randomized to receive additional miglitol or placebo for 24 weeks, titrated up stepwise from 25 to 100 mg trice daily. RESULTS: Addition of miglitol to sulphonylureas and metformin (per protocol analysis) produced a statistically, significantly greater reduction in HbA1c (-0.55%, P = 0.04) and postprandial glucose (-2.6 mmol/l, P = 0.0009) from baseline to endpoint than placebo (-0.2% and -0.6 mol/l, respectively). Reduction in fasting blood glucose was greater with miglitol than placebo, and there was a possible difference in favor of miglitol for fasting and postprandial triglyceride levels, but these did not reach statistical significance. Flatulence and diarrhea were reported by statistically, significantly more patients receiving miglitol than placebo, but adverse events overall were reported by only 10% more patients in the miglitol group. No cases of hypoglycaemia were reported. CONCLUSIONS: Miglitol can safely and effectively be added to long-term combination therapy in people with Type 2 diabetes inadequately controlled with glibenclamide plus metformin.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Since folate and vitamin B12 absorption may be increased by colonic bacterial activity, their status may be improved by miglitol, an α-glucosidase inhibitor of potential use in the treatment of diabetes. To test this, subjects with type 2 diabetes were treated for 9 months in a double-blind, randomized controlled fashion with either placebo (n=45), miglitol (n=45), metformin (n=62), or a combination of miglitol and metformin (n=47). Glycated hemoglobin (HbA1c), serum and red cell folate and serum vitamin B12 were measured and 3-day dietary records obtained before and after therapy. Compared to placebo, all 3 active treatments significantly reduced HbA1c, metformin to a greater extent than miglitol and the combination to a greater extent than metformin. Dietary folate intake did not change on any treatment. Serum folate and vitamin B12, respectively, did not change on placebo, but fell by 14% and 15% on metformin and rose by 12% and 23% on miglitol. The changes in folate and vitamin B12 concentrations on metformin were significantly different from those on miglitol. On combination therapy, both folate and vitamin B12 tended to rise, but the difference from metformin was only significant for folate. These data support the hypothesis that increased carbohydrate delivery to the colon increases intestinal biosynthesis of folate. The combination of miglitol with metformin may prevent the metformin-induced fall in serum folate and vitamin B12.

AIMS: A double-blind randomised study was performed to compare the dose-effect and dose-tolerability relationships between the alpha-glucosidase inhibitor miglitol in doses of 25 mg, 50 mg, 100 mg and 200 mg all t.i.d. vs placebo t.i.d. in patients with Type 2 diabetes mellitus on diet only. METHODS: After a 6-week placebo run-in period 468 patients with a fasting blood glucose > or = 7 mmol/l as well as a HbA1c between 6.1% and 10.4% were randomised for a 24-week treatment period. RESULTS: The results of 465 patients were valid for safety analysis and of 384 patients for the efficacy analysis. In the placebo group the HbA1c level increased by 0.40+/-1.46% as compared with baseline. The decrease in the mean HbA1c values (corrected for differences in baseline values) was significant and dose-dependent for all miglitol groups compared with placebo, being -0.46% (95% CI: -0.91%, -0.01%) in the 25 mg group, -0.45% (95% CI: -0.90%, -0.003%) in the 50 mg group, -0.84% (95% CI: -1.31%, -0.37%) in the 100 mg group and -1.26% (95% CI: -1.76%, -0.76%) in the 200 mg group. Blood glucose levels following a standardised breakfast tolerance test were significantly and dose-dependently lower for all the miglitol doses at 12 and 24 wk of treatment compared to baseline: in comparison with baseline maximum blood glucose increased by 4% with placebo and decreased by 7%, 14%, 24% and 33% with miglitol 25 mg, 50 mg, 100 mg and 200 mg t.i.d. respectively. The same pattern was seen with postprandial maximal serum insulin levels which decreased by 8% under placebo and by 17%, 26%, 25% and 35% with the 25 mg to 200 mg doses of miglitol. The adverse events reported were mainly of gastrointestinal nature, mostly being flatulence, diarrhoea and abdominal pain and the incidence increased with increasing dose. Although the side effects were not serious, they were troublesome, leading to a considerable drop-out rate increasing with dose. CONCLUSIONS: The alpha-glucosidase inhibitor miglitol in Type 2 diabetic patients on diet alone decreases both HbA1c levels and postprandial glucose and insulin levels in a dose-dependent manner. Gastrointestinal side effects also showed dose-dependency. Combination of efficacy and safety results leads to the conclusion that the optimal dose of miglitol will be in the range of 50 to 100 mg t.i.d.

OBJECTIVE: To determine the efficacy of the alpha-glucosidase inhibitor miglitol (BAYm 1099) regarding the starch content of food. RESEARCH DESIGN AND METHODS: Thirty-six non-insulin-dependent diabetes mellitus (NIDDM) subjects were studied in a double-blind randomized study comparing treatment with a single dosage of 100 mg miglitol or placebo and a single-blind crossover comparison of three test meals in which the carbohydrate contained either 30, 50, or 70% starch, and quantities of fat and protein were kept constant. RESULTS: Postprandial blood glucose excursions were reduced by approximately 50% with miglitol after all test meals. In contrast, after miglitol treatment, maximum postprandial serum C-peptide and insulin values reached the same levels as after placebo treatment, although the time to reach these maximum levels was delayed. Free fatty acid values decreased after both miglitol and placebo similarly. Twenty-eight untoward events in 15 patients were reported in the miglitol treatment group and 11 events in 7 patients in the placebo treatment group. CONCLUSIONS: Miglitol reduces postprandial blood glucose excursions independent of the starch content of the meal. Because no effects were found on incremental postprandial maximal levels of serum insulin and C-peptide, it may be that miglitol exerts, in addition to a delay of intestinal carbohydrate absorption, extraintestinal effects as well, particularly effects on disposition of glucose or anti-insulin counterregulatory factors.

To investigate the efficacy and safety of miglitol in Japanese patients with type 2 diabetes that is insufficiently controlled diet alone.

OBJECTIVE: We compared the efficacy and safety of taking miglitol dissolved in water during a meal and taking a miglitol tablet just before a meal. Primary efficacy parameter is the area under the curve (AUC) for postprandial plasma glucose. METHODS: Miglitol was administered according to three different intake schedules in each subject: intake schedule A, no miglitol; intake schedule B, administration of miglitol (50 mg) just before breakfast; intake schedule C, dissolving miglitol (50 mg) in water and taking it just before (1/3), during (1/3), and just after breakfast (1/3). Blood samples were collected at 0, 30, 60, 120, and 180 min after breakfast. RESULTS: The AUCs for plasma glucose, insulin, and total glucose-dependent insulinotropic polypeptide (GIP) were significantly lower for intake schedules B and C, compared with those for intake schedule A. The AUC for total glucagon like peptide-1(GLP-1) was higher for intake schedule C than for intake schedule A. The coefficient of variation (CV) of plasma glucose was significantly lower for intake schedule C than for intake schedules A and B. CONCLUSION: Taking miglitol dissolved in water was equivalent to taking a miglitol tablet. The CV of plasma glucose was significantly lower for the dissolved-dose regimen.