CLINICAL STUDIES
Clinical Experience in Non-Insulin-Dependent Diabetes Mellitus (NIDDM) Patients on Dietary Treatment Only
GLYSET Tablets were evaluated in two U.S. and three non-U.S. controlled, fixed-dose, monotherapy studies, in which 735 patients treated with GLYSET were evaluated for efficacy analyses (see Table 1).
In Study 1, a 1-year study in which GLYSET was evaluated as monotherapy and also as combination therapy, there was a statistically significantly smaller increase in mean glycosylated hemoglobin (HbA1c) over time in the miglitol 50 mg 3 times daily monotherapy arm compared to placebo. Significant reductions in mean fasting and postprandial plasma glucose levels and in mean postprandial insulin levels were observed in patients treated with GLYSET compared with the placebo group.
In Study 2, a 14-week study, there was a significant decrease in HbA1c in patients receiving GLYSET 50 mg 3 times daily or 100 mg 3 times daily compared to placebo. In addition, there were significant reductions in postprandial plasma glucose and postprandial serum insulin levels compared to placebo.
Study 3, was a 6-month dose-ranging trial evaluating GLYSET at doses from 25 mg 3 times daily, to 200 mg 3 times daily. GLYSET produced a greater reduction in HbA1c than placebo at all doses, although the effect was statistically significant at the 100 mg 3 times daily and 200 mg 3 times daily. In addition, all doses of GLYSET produced significant reductions in postprandial plasma glucose and postprandial insulin levels compared to placebo.
Studies 4 and 5 were 6-month studies evaluating GLYSET at 50 and 100 mg 3 times daily, and 100 mg 3 times daily, respectively. As compared to placebo, GLYSET produced reductions in HbA1c, as well as a significant reduction in postprandial plasma glucose in both studies at the doses employed.
| HbA1c (%) | 1-hour Postprandial Glucose (mg/dL) | ||||
|---|---|---|---|---|---|
| Study | Treatment | Mean Change from Baseline* | Treatment Effect† | Mean Change from Baseline | Treatment Effect† |
| 1 (U.S.) | Placebo | +0.71 | --- | +24 | --- |
| GLYSET 50 mg 3 times daily | +0.13 | -0.58‡ | -39 | -63‡ | |
| 2 (U.S.) | Placebo | +0.47 | --- | +15 | --- |
| GLYSET 50 mg 3 times daily | -0.22 | -0.69‡ | -52 | -67‡ | |
| GLYSET 100 mg 3 times daily | -0.28 | -0.75‡ | -59 | -74‡ | |
| 3 (non-U.S.) | Placebo | +0.18 | --- | +2 | --- |
| GLYSET 25 mg 3 times daily | -0.08 | -0.26 | -33 | -35‡ | |
| GLYSET 50 mg 3 times daily | -0.22 | -0.40 | -45 | -47‡ | |
| GLYSET 100 mg 3 times daily | -0.63 | -0.81‡ | -62 | -64‡ | |
| GLYSET 200 mg 3 times daily § | -0.84 | -1.02‡ | -85 | -87‡ | |
| 4 (non-U.S.) | Placebo | +0.01 | --- | +8 | --- |
| GLYSET 50 mg 3 times daily | -0.35 | -0.36‡ | -20 | -28‡ | |
| GLYSET 100 mg 3 times daily | -0.57 | -0.58‡ | -25 | -33‡ | |
| 5 (non-U.S.) | Placebo | +0.32 | --- | +17 | --- |
| GLYSET 100 mg 3 times daily | -0.43 | -0.75‡ | -38 | -55‡ | |
Clinical Experience in NIDDM Patients Receiving Sulfonylureas
GLYSET was studied as adjunctive therapy to a background of maximal or near-maximal sulfonylurea (SFU) treatment in three large, double-blind, randomized studies (two U.S. and one non-U.S.) in which 471 patients treated with GLYSET were evaluated for efficacy (see Table 2).
Study 6 included patients under treatment with maximal doses of SFU at entry. At the end of this 14-week study, the mean treatment effects on glycosylated hemoglobin (HbA1c) were -0.82% and -0.74% for patients receiving GLYSET 50 mg 3 times daily plus SFU, and GLYSET 100 mg 3 times daily plus SFU, respectively.
Study 7 was a 1-year study in which GLYSET at 25, 50 or 100 mg 3 times daily was added to a maximal dose of glyburide (10 mg twice daily). At the end of this study, the mean treatment effects on HbA1c of GLYSET when added to maximum glyburide therapy were -0.30%, -0.62%, and -0.73% with 25, 50 and 100 mg 3 times daily dosages of GLYSET, respectively.
In Study 8, the addition of GLYSET 100 mg 3 times daily to a background of treatment with glyburide produced an additional mean treatment effect on HbA1c of -0.66%.
| HbA1c (%) | 1-hour Postprandial Glucose (mg/dL) | ||||
|---|---|---|---|---|---|
| Study | Treatment | Mean Change from Baseline* | Treatment Effect† | Mean Change from Baseline | Treatment Effect† |
| 6 (U.S.) | Placebo + SFU | +0.33 | --- | -1 | --- |
| GLYSET 50 mg 3 times daily + SFU | -0.49 | -0.82‡ | -69 | -68‡ | |
| GLYSET 100 mg 3 times daily + SFU | -0.41 | -0.74‡ | -73 | -72‡ | |
| 7 (U.S.) | Placebo + SFU | +1.01 | --- | 48 | --- |
| GLYSET 25 mg 3 times daily + SFU | +0.71 | -0.30 | -2 | -50‡ | |
| GLYSET 50 mg 3 times daily + SFU | +0.39 | -0.62‡ | -13 | -61‡ | |
| GLYSET 100 mg 3 times daily + SFU | +0.28 | -0.73‡ | -33 | -81‡ | |
| 8 (non-U.S.) | Placebo + SFU | +0.16 | --- | +10 | --- |
| GLYSET 100 mg 3 times daily + SFU | -0.50 | -0.66‡ | -36 | -46‡ | |
Dose Response
Results from controlled, fixed-dose studies of GLYSET as monotherapy or as combination treatment with a sulfonylurea were combined to derive a pooled estimate of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) and postprandial plasma glucose as shown in Figures 1 and 2:
Because of its mechanism of action, the primary pharmacologic effect of miglitol is manifested as a reduction in postprandial plasma glucose, as shown previously in all of the major clinical trials. GLYSET was statistically significantly different from placebo at all doses in each of the individual studies with respect to effect on mean one-hour postprandial plasma glucose, and there is a dose response from 25 to 100 mg 3 times daily for this efficacy parameter.