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Adults with type 2 diabetes: 850 mg single dose (23) 1.48 (± 0.5) 3.32 (± 1.08) 491 (± 138) 850 mg three times daily for 1.90 (± 0.62) 2.01 (± 1.22) 550 (± 160)
19 doses e (9) Elderly f , healthy nondiabetic adults: 850 mg single dose (12) 2.45 (± 0.70) 2.71 (± 1.05) 412 (± 98) Text Continues Below
Renal-impaired adults: 850 mg single dose
Mild (CL cr g 61-90 mL/ min) (5) 1.86 (± 0.52) 3.20 (± 0.45) 384 (± 122) Moderate (CL
cr 31-60 mL/ min) (4) 4.12 (± 1.83) 3.75 (± 0.50) 108 (± 57) Severe (CL
cr 10-30 mL/ min) (6) 3.93 (± 0.92) 4.01 (± 1.10) 130 (± 90) Table 2. GLUCOPHAGE vs Placebo
Summary of Mean Changes from Baseline* in Fasting Plasma Glucose, HbA
1c and Body Weight, at Final Visit (29-week study)
GLUCOPHAGE Placebo p-Value (n = 141) (n = 145) FPG (mg/ dL)
Baseline 241.5 237.7 NS**
Change at FINAL VISIT -53.0 6.3 0.001
Hemoglobin A 1c (%)
Baseline 8.4 8.2 NS**
Change at FINAL VISIT -1.4 0.4 0.001
Body Weight (lbs)
Baseline 201.0 206.0 NS**
Change at FINAL VISIT -1.4 -2.4 NS** A 29-week, double-blind, placebo-controlled study of GLUCOPHAGE and glyburide, alone and in combination, was conducted in obese patients with type 2 diabetes who had failed to achieve adequate glycemic control while on maximum doses of glyburide (baseline FPG of approximately 250 mg/ dL) (see Table 3). Patients randomized to the combination arm started therapy with GLUCOPHAGE 500 mg and glyburide 20 mg. At the end of each week of the first four weeks of the trial, these patients had their dosages of GLUCOPHAGE increased by 500 mg if they had failed to reach target fasting plasma glucose. After week four, such dosage adjustments were made monthly, although no patient was allowed to exceed GLUCOPHAGE 2500 mg. Patients in the GLUCOPHAGE only arm (metformin plus placebo) followed the same titration schedule. At the end of the trial, approx-imately 70% of the patients in the combination group were taking GLUCOPHAGE 2000 mg/ glyburide 20 mg or GLUCOPHAGE 2500 mg/ glyburide 20 mg. Patients randomized to continue on glyburide experienced worsening of glycemic control, with mean increases in FPG, PPG, and HbA 1c of 14 mg/ dL, 3 mg/ dL and 0.2%, respectively. In contrast, those randomized to GLUCOPHAGE (up to 2500 mg/ day) experienced a slight improvement, with mean reductions in FPG, PPG, and HbA 1c of 1 mg/ dL, 6 mg/ dL and 0.4%, respectively. The combination of GLUCOPHAGE and glyburide was effective in reducing FPG, PPG, and HbA 1c levels by 63 mg/ dL, 65 mg/ dL, and 1.7%, respectively. Compared to results of glyburide treatment alone, the net differences with combination treatment were -77 mg/ dL, -68 mg/ dL and -1.9%, respectively (see Table 3). *All patients on glyburide, 20 mg/ day, at Baseline ** Not statistically significant The magnitude of the decline in fasting blood glucose concentration following the institution of GLUCOPHAGE (metformin hydrochloride tablets) therapy was proportional to the level of fasting hyperglycemia. Patients with type 2 diabetes with higher fasting glucose concentrations experienced greater declines in plasma glucose and glycosylated hemoglobin. In clinical studies, GLUCOPHAGE, alone or in combination with a sulfonylurea, lowered mean fast-ing serum triglycerides, total cholesterol, and LDL cholesterol levels and had no adverse effects on other lipid levels (see Table 4). In contrast to sulfonylureas, body weight of individuals on GLUCOPHAGE tended to remain stable or even decrease somewhat (see Tables 2 and 3). A 24-week, double-blind, placebo-controlled study of GLUCOPHAGE plus insulin versus insulin plus placebo was conducted in patients with type 2 diabetes who failed to achieve adequate glycemic control on insulin alone (see Table 5). Patients randomized to receive GLUCOPHAGE plus insulin achieved a reduction in HbA 1c of 2.10%, compared to a 1.56% reduction in HbA 1c achieved by insulin plus placebo. The improvement in glycemic control was achieved at the final study visit with 16% less insulin, 93.0 U/ day vs 110.6 U/ day, GLUCOPHAGE plus insulin versus insulin plus placebo, respectively, p= 0.04. a Statistically significant using analysis of covariance with baseline as covariate (p= 0.04) Not significant using analysis of variance (values shown in table) b Statistically significant for insulin (p= 0.04) A second double-blind, placebo-controlled study (n= 51), with 16 weeks of randomized treatment, demonstrated that in patients with type 2 diabetes controlled on insulin for 8 weeks with an aver-age HbA 1c of 7.46 ± 0.97%, the addition of GLUCOPHAGE maintained similar glycemic control (HbA 1c 7.15 ± 0.61 versus 6.97 ± 0.62 for GLUCOPHAGE plus insulin and placebo plus insulin, respectively) with 19% less insulin versus baseline (reduction of 23.68 ± 30.22 versus an increase of 0.43 ± 25.20 units for GLUCOPHAGE plus insulin and placebo plus insulin, p< 0.01). In addition, this study demonstrated that the combination of GLUCOPHAGE (metformin hydrochloride tablets) plus insulin resulted in reduction in body weight of 3.11 ± 4. 30 lbs, compared to an increase of 1.30 ± 6.08 lbs for placebo plus insulin, p= 0.01. GLUCOPHAGE XR A 24-week, double-blind, placebo-controlled study of GLUCOPHAGE XR, taken once daily with the evening meal, was conducted in patients with type 2 diabetes who had failed to achieve glycemic control with diet and exercise (HbA 1c 7.0-10.0%, FPG 126-270 mg/ dL). Patients entering the study had a mean baseline HbA 1c of 8.0% and a mean baseline FPG of 176 mg/ dL. After 12 weeks treat-ment, mean HbA 1c had increased from baseline by 0.1% and mean FPG decreased from baseline by 2 mg/ dL in the placebo group, compared with a decrease in mean HbA 1c of 0.6% and a decrease in mean FPG of 23 mg/ dL in patients treated with GLUCOPHAGE XR 1000 mg once daily. Subsequently, the treatment dose was increased to 1500 mg once daily if HbA 1c was 7.0% but <8.0% (patients with HbA 1c 8.0% were discontinued from the study). At the final visit (24-week), mean HbA 1c had increased 0.2% from baseline in placebo patients and decreased 0.6% with GLUCOPHAGE XR (metformin hydrochloride extended-release tablets). A 16-week, double-blind, placebo-controlled, dose-response study of GLUCOPHAGE XR, taken once daily with the evening meal, or twice daily with meals, was conducted in patients with type 2 diabetes who had failed to achieve glycemic control with diet and exercise (HbA 1c 7.0-11%, FPG 126-280 mg/ dL). Changes in glycemic control and body weight are shown in Table 6. * All patients on diet therapy at Baseline a
All comparisons versus Placebo
** Not statistically significant Compared with placebo, improvement in glycemic control was seen at all dose levels of GLUCOPHAGE XR and treatment was not associated with any significant change in weight (see DOSAGE AND ADMINISTRATION for dosing recommendations for GLUCOPHAGE and GLUCOPHAGE XR). A 24-week, double-blind, randomized study of GLUCOPHAGE XR, taken once daily with the evening meal, and GLUCOPHAGE, taken twice daily (with breakfast and evening meal), was con-ducted in patients with type 2 diabetes who had been treated with GLUCOPHAGE 500 mg twice daily for at least 8 weeks prior to study entry. The GLUCOPHAGE dose had not necessarily been titrated to achieve a specific level of glycemic control prior to study entry. Patients qualified for the study if HbA 1c was 8.5% and FPG was 200 mg/ dL. Changes in glycemic control and body weight are shown in Table 7. * All patients on GLUCOPHAGE 500 mg twice daily at Baseline a
n= 68 After 12 weeks of treatment, there was an increase in mean HbA 1c in all groups; in the GLUCOPHAGE XR 1000 mg group, the increase from baseline of 0.23% was statistically signifi-cant (see DOSAGE AND ADMINISTRATION). Table 3. Combined GLUCOPHAGE/ Glyburide (Comb) vs Glyburide (Glyb) or GLUCOPHAGE (GLU) Monotherapy: Summary of Mean Changes from Baseline*
in Fasting Plasma Glucose, HbA 1c and Body Weight, at Final Visit (29-week study) p-values Comb Glyb GLU Glyb vs GLU vs GLU vs (n = 213) (n = 209) (n = 210) Comb Comb Glyb
Fasting Plasma Glucose (mg/ dL) Baseline 250.5 247.5 253.9 NS** NS** NS**
Change at FINAL VISIT -63.5 13.7 -0.9 0.001 0.001 0.025 Hemoglobin A 1c (%)
Baseline 8.8 8.5 8.9 NS** NS** 0.007
Change at FINAL VISIT -1.7 0.2 -0.4 0.001 0.001 0.001 Body Weight (lbs)
Baseline 202.2 203.0 204.0 NS** NS** NS**
Change at FINAL VISIT 0.9 -0.7 -8.4 0.011 0.001 0.001 Table 6. Summary of Mean Changes from Baseline* in HbA 1c , Fasting Plasma Glucose, and Body Weight at Final Visit (16-week study)
GLUCOPHAGE XR Placebo
500 mg 1000 mg 1500 mg 2000 mg 1000 mg Once Once Once Once Twice Daily Daily Daily Daily Daily
Hemoglobin A 1c (%) (n= 115) (n= 115) (n= 111) (n= 125) (n= 112) (n= 111) Baseline 8.2 8.4 8.3 8.4 8.4 8.4 Change at FINAL VISIT -0.4 -0.6 -0.9 -0.8 -1.1 0.1
p-value a <0.001 <0.001 <0.001 <0.001 <0.001 -FPG (mg/ dL) (n= 126) (n= 118) (n= 120) (n= 132) (n= 122) (n= 113) Baseline 182.7 183.7 178.9 181.0 181.6 179.6 Change at FINAL VISIT -15.2 -19.3 -28.5 -29.9 -33.6 7.6
p-value a <0.001 <0.001 <0.001 <0.001 <0.001 -Body Weight (lbs) (n= 125) (n= 119) (n= 117) (n= 131) (n= 119) (n= 113) Baseline 192.9 191.8 188.3 195.4 192.5 194.3 Change at FINAL VISIT -1.3 -1.3 -0.7 -1.5 -2.2 -1.8
p-value a NS** NS** NS** NS** NS** -Table 7. Summary of Mean Changes from Baseline* in HbA 1c , Fasting Plasma Glucose, and Body Weight at Week 12 and at Final Visit (24-week study)
GLUCOPHAGE GLUCOPHAGE XR
500 mg Twice Daily 1000 mg Once Daily 1500 mg Once Daily
Hemoglobin A 1c (%) (n= 67) (n= 72) (n= 66)
Baseline 7.06 6.99 7.02
Change at 12 Weeks 0.14 0.23 0.04
(95% CI) (-0.03, 0.31) (0.10, 0.36) (-0.08, 0.15)
Change at FINAL VISIT 0.14 a 0.27 0.13
(95% CI) (-0.04, 0.31) (0.11, 0.43) (-0.02, 0.28)
FPG (mg/ dL) (n= 69) (n= 72) (n= 70)
Baseline 127.2 131.0 131.4
Change at 12 Weeks 12.9 9.5 3.7
(95% CI) (6.5, 19.4) (4.4, 14.6) (-0.4, 7.8)
Change at FINAL VISIT 14.0 11.5 7.6
(95% CI) (7.0, 21.0) (4.4, 18.6) (1.0, 14.2)
Body Weight (lbs) (n= 71) (n= 74) (n= 71)
Baseline 210.3 202.8 192.7
Change at 12 Weeks 0.4 0.9 0.7
(95% CI) (-0.4, 1.5) (0.0, 2.0) (-0.4, 1.8)
Change at FINAL VISIT 0.9 1.1 0.9
(95% CI) (-0.4, 2.2) (-0.2, 2.4) (-0.4, 2.0) Table 4. Summary of Mean Percent Change from Baseline of Major Serum Lipid Variables at Final Visit (29-week studies)
Combined GLUCOPHAGE/ Glyburide GLUCOPHAGE vs Placebo vs Monotherapy
GLUCOPHAGE/ GLUCOPHAGE Placebo GLUCOPHAGE Glyburide Glyburide
(n = 141) (n = 145) (n = 210) (n = 213) (n = 209)
Total Cholesterol (mg/ dL)
Baseline 211.0 212.3 213.1 215.6 219.6
Mean % change
at FINAL VISIT -5% 1% -2% -4% 1% Total Triglycerides (mg/ dL)
Baseline 236.1 203.5 242.5 215.0 266.1
Mean % change
at FINAL VISIT -16% 1% -3% -8% 4% LDL-Cholesterol (mg/ dL)
Baseline 135.4 138.5 134.3 136.0 137.5
Mean % change
at FINAL VISIT -8% 1% -4% -6% 3% HDL-Cholesterol (mg/ dL)
Baseline 39.0 40.5 37.2 39.0 37.0
Mean % change
at FINAL VISIT 2% -1% 5% 3% 1% Table 5. Combined GLUCOPHAGE/ Insulin vs Placebo/ Insulin Summary of Mean Changes from Baseline in HbA
1c and Daily Insulin Dose
GLUCOPHAGE/ Insulin Placebo/ Insulin Treatment difference n= 26 n= 28 Mean ± SE Hemoglobin A 1c (%)
Baseline 8.95 9.32
Change at FINAL VISIT -2.10 -1.56 -0.54 ± 0.43 a
Insulin Dose (U/ day)
Baseline 93.12 94.64
Change at FINAL VISIT -0.15 15.93 -16.08 ± 7.77 b Changes in lipid parameters in the previously described placebo-controlled dose-response study of GLUCOPHAGE XR are shown in Table 8. * All patients on diet therapy at Baseline
Changes in lipid parameters in the previously described study of GLUCOPHAGE and GLUCOPHAGE XR are shown in Table 9. * All patients on GLUCOPHAGE 500 mg twice daily at Baseline
Pediatric Clinical Studies In a double-blind, placebo-controlled study in pediatric patients aged 10 to 16 years with type 2 diabetes (mean FPG 182.2 mg/ dL), treatment with GLUCOPHAGE (up to 2000 mg/ day) for up to 16 weeks (mean duration of treatment 11 weeks) resulted in a significant mean net reduction in FPG of 64.3 mg/ dL, compared with placebo (see Table 10). a Pediatric patients mean age 13.8 years (range 10-16 years)
* All patients on diet therapy at Baseline
** Not statistically significant Page: << Prev | 1 | 2 | 3 | 4 | 5
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