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Glucophage, Glucophage XR

CLINICAL PHARMACOLOGY

Mechanism of Action

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacologic mechanisms of action are different from other classes of oral antihyperglycemic agents. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects (except in special circumstances, see PRECAUTIONS) and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.

Pharmacokinetics

Absorption and Bioavailability

The absolute bioavailability of a GLUCOPHAGE 500 mg tablet given under fasting conditions is approximately 50% to 60%. Studies using single oral doses of GLUCOPHAGE 500 to 1500 mg, and 850 to 2550 mg, indicate that there is a lack of dose proportionality with increasing doses, which is due to decreased absorption rather than an alteration in elimination. Food decreases the extent of and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak plasma concentration (Cmax), a 25% lower area under the plasma concentration versus time curve (AUC), and a 35-minute prolongation of time to peak plasma concentration (Tmax) following administration of a single 850 mg tablet of metformin with food, compared to the same tablet strength administered fasting. The clinical relevance of these decreases is unknown.

Following a single oral dose of GLUCOPHAGE XR, Cmax is achieved with a median value of 7 hours and a range of 4 to 8 hours. Peak plasma levels are approximately 20% lower compared to the same dose of GLUCOPHAGE, however, the extent of absorption (as measured by AUC) is similar to GLUCOPHAGE.

At steady state, the AUC and Cmax are less than dose proportional for GLUCOPHAGE XR within the range of 500 to 2000 mg administered once daily. Peak plasma levels are approximately 0.6, 1.1, 1.4, and 1.8 μg/mL for 500, 1000, 1500, and 2000 mg once-daily doses, respectively. The extent of metformin absorption (as measured by AUC) from GLUCOPHAGE XR at a 2000 mg once-daily dose is similar to the same total daily dose administered as GLUCOPHAGE tablets 1000 mg twice daily. After repeated administration of GLUCOPHAGE XR, metformin did not accumulate in plasma.

Within-subject variability in Cmax and AUC of metformin from GLUCOPHAGE XR is comparable to that with GLUCOPHAGE.

Although the extent of metformin absorption (as measured by AUC) from the GLUCOPHAGE XR tablet increased by approximately 50% when given with food, there was no effect of food on Cmax and Tmax of metformin. Both high and low fat meals had the same effect on the pharmacokinetics of GLUCOPHAGE XR.

Distribution

The apparent volume of distribution (V/F) of metformin following single oral doses of GLUCOPHAGE 850 mg averaged 654 ± 358 L. Metformin is negligibly bound to plasma proteins, in contrast to sulfonylureas, which are more than 90% protein bound. Metformin partitions into erythrocytes, most likely as a function of time. At usual clinical doses and dosing schedules of GLUCOPHAGE, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally < 1 μg/mL. During controlled clinical trials of GLUCOPHAGE, maximum metformin plasma levels did not exceed 5 μg/mL, even at maximum doses.

Metabolism and Elimination

Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Renal clearance (see Table 1) is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half-life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.

Special Populations

Patients with Type 2 Diabetes

In the presence of normal renal function, there are no differences between single- or multiple-dose pharmacokinetics of metformin between patients with type 2 diabetes and normal subjects (see Table 1), nor is there any accumulation of metformin in either group at usual clinical doses.

The pharmacokinetics of GLUCOPHAGE XR in patients with type 2 diabetes are comparable to those in healthy normal adults.

Renal Insufficiency

In patients with decreased renal function (based on measured creatinine clearance), the plasma and blood half-life of metformin is prolonged and the renal clearance is decreased in proportion to the decrease in creatinine clearance (see Table 1; also see WARNINGS).

Hepatic Insufficiency

No pharmacokinetic studies of metformin have been conducted in patients with hepatic insufficiency.

Geriatrics

Limited data from controlled pharmacokinetic studies of GLUCOPHAGE in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, the half-life is prolonged, and Cmax is increased, compared to healthy young subjects. From these data, it appears that the change in metformin pharmacokinetics with aging is primarily accounted for by a change in renal function (see Table 1). GLUCOPHAGE (metformin hydrochloride) Tablets and GLUCOPHAGE XR (metformin hydrochloride) Extended-Release Tablets treatment should not be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced (see WARNINGS and DOSAGE AND ADMINISTRATION).

Table 1: Select Mean (±S.D.) Metformin Pharmacokinetic Parameters Following Single or Multiple Oral Doses of GLUCOPHAGE

Subject Groups: GLUCOPHAGE dosea (number of subjects) Cmaxb
(μg/mL)
Tmaxc
(hrs)
Renal Clearance
(mL/min)
Healthy, nondiabetic adults:
  500 mg single dose (24) 1.03 (±0.33) 2.75 (±0.81) 600 (±132)
  850 mg single dose (74)d 1.60 (±0.38) 2.64 (±0.82) 552 (±139)
  850 mg three times daily for 19 dosese (9) 2.01 (±0.42) 1.79 (±0.94) 642 (±173)
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 19 dosese (9) 1.90 (±0.62) 2.01 (±1.22) 550 (±160)
Elderlyf, healthy nondiabetic adults:
  850 mg single dose (12) 2.45 (±0.70) 2.71 (±1.05) 412 (±98)
Renal-impaired adults: 850 mg single dose
  Mild (CLcrg 61-90 mL/min) (5) 1.86 (±0.52) 3.20 (±0.45) 384 (±122)
  Moderate (CLcr 31-60 mL/min) (4) 4.12 (±1.83) 3.75 (±0.50) 108 (±57)
  Severe (CLcr 10-30 mL/min) (6) 3.93 (±0.92) 4.01 (±1.10) 130 (±90)
a All doses given fasting except the first 18 doses of the multiple dose studies
b Peak plasma concentration
c Time to peak plasma concentration
d Combined results (average means) of five studies: mean age 32 years (range 23-59 years)
eKinetic study done following dose 19, given fasting
f Elderly subjects, mean age 71 years (range 65-81 years)
g CLcr = creatinine clearance normalized to body surface area of 1.73 m²

Pediatrics

After administration of a single oral GLUCOPHAGE 500 mg tablet with food, geometric mean metformin Cmax and AUC differed less than 5% between pediatric type 2 diabetic patients (12-16 years of age) and gender- and weight-matched healthy adults (20-45 years of age), all with normal renal function.

Gender

Metformin pharmacokinetic parameters did not differ significantly between normal subjects and patients with type 2 diabetes when analyzed according to gender (males = 19, females = 16). Similarly, in controlled clinical studies in patients with type 2 diabetes, the antihyperglycemic effect of GLUCOPHAGE was comparable in males and females.

Race

No studies of metformin pharmacokinetic parameters according to race have been performed. In controlled clinical studies of GLUCOPHAGE in patients with type 2 diabetes, the antihyperglycemic effect was comparable in whites (n=249), blacks (n=51), and Hispanics (n=24).

Clinical Studies

Glucophage

In a double-blind, placebo-controlled, multicenter US clinical trial involving obese patients with type 2 diabetes whose hyperglycemia was not adequately controlled with dietary management alone (baseline fasting plasma glucose [FPG] of approximately 240 mg/dL), treatment with GLUCOPHAGE (up to 2550 mg/day) for 29 weeks resulted in significant mean net reductions in fasting and postprandial plasma glucose (PPG) and hemoglobin A1c (HbA1c) of 59 mg/dL, 83 mg/dL, and 1.8%, respectively, compared to the placebo group (see Table 2).

Table 2: GLUCOPHAGE vs Placebo Summary of Mean Changes from Baseline* in Fasting Plasma Glucose, HbA1c, and Body Weight, at Final Visit (29-week study)

  GLUCOPHAGE
(n=141)
Placebo
(n=145)
p-Value
FPG (mg/dL)
  Baseline 241.5 237.7 NS**
  Change at FINAL VISIT –53.0 6.3 0.001
Hemoglobin A1c (%)
  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**
* All patients on diet therapy at Baseline
** Not statistically significant

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 4 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 4, 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, approximately 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 HbA1c 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 HbA1c of 1 mg/dL, 6 mg/dL, and 0.4%, respectively. The combination of GLUCOPHAGE and glyburide was effective in reducing FPG, PPG, and HbA1c 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).

Table 3: Combined GLUCOPHAGE/Glyburide (Comb) vs Glyburide (Glyb) or GLUCOPHAGE (GLU) Monotherapy: Summary of Mean Changes from Baseline* in Fasting Plasma Glucose, HbA1c, and Body Weight, at Final Visit (29-week study)

  Comb
(n=213)
Glyb
(n=209)
GLU
(n=210)
p-values
Glyb vs
Comb
GLU vs
Comb
GLU vs
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 A1c (%)
  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
* 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 fasting serum triglycerides, total cholesterol, and LDL cholesterol levels, and had no adverse effects on other lipid levels (see Table 4).

Table 4: Summary of Mean Percent Change From Baseline of Major Serum Lipid Variables at Final Visit (29-week studies)

  GLUCOPHAGE vs Placebo Combined GLUCOPHAGE/ Glyburide vs Monotherapy
GLUCOPHAGE
(n=141)
Placebo
(n=145)
GLUCOPHAGE
(n=210)
GLUCOPHAGE/
Glyburide
(n=213)
Glyburide
(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%

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 HbA1c of 2.10%, compared to a 1.56% reduction in HbA1c 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.

Table 5: Combined GLUCOPHAGE/Insulin vs Placebo/Insulin Summary of Mean Changes from Baseline in HbA1c and Daily Insulin Dose

  GLUCOPHAGE/
Insulin
(n=26)
Placebo/
Insulin
(n=28)
Treatment
Difference
Mean ± SE
Hemoglobin A1c (%)
  Baseline 8.95 9.32  
  Change at FINAL VISIT –2.10 –1.56 –0.54 ± 0.43a
Insulin Dose (U/day)
  Baseline 93.12 94.64  
  Change at FINAL VISIT –0.15 15.93 –16.08 ± 7.77b
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 average HbA1c of 7.46 ± 0.97%, the addition of GLUCOPHAGE maintained similar glycemic control (HbA1c 7.15 ± 0.61 vs 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 vs 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 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 (HbA1c 7.0%-10.0%, FPG 126-270 mg/dL). Patients entering the study had a mean baseline HbA1c of 8.0% and a mean baseline FPG of 176 mg/dL. After 12 weeks treatment, mean HbA1c 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 HbA1c 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 HbA1c was ≥ 7.0% but < 8.0% (patients with HbA1c ≥ 8.0% were discontinued from the study). At the final visit (24-week), mean HbA1c had increased 0.2% from baseline in placebo patients and decreased 0.6% with GLUCOPHAGE XR.

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 (HbA1c 7.0%-11.0%, FPG 126-280 mg/dL). Changes in glycemic control and body weight are shown in Table 6.

Table 6: Summary of Mean Changes from Baseline* in HbA1c, Fasting Plasma Glucose, and Body Weight at Final Visit (16-week study)

  GLUCOPHAGE XR Placebo
500 mg
Once Daily
1000 mg
Once Daily
1500 mg
Once Daily
2000 mg
Once Daily
1000 mg
Twice Daily
Hemoglobin A1c (%) (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-valuea < 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-valuea < 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-valuea NS** NS** NS** NS** NS**
* 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 (metformin hydrochloride) Extended-Release Tablets 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 (metformin hydrochloride) Tablets, taken twice daily (with breakfast and evening meal), was conducted 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 HbA1c was ≤ 8.5% and FPG was ≤ 200 mg/dL. Changes in glycemic control and body weight are shown in Table 7.

Table 7: Summary of Mean Changes from Baseline* in HbA1c, Fasting Plasma Glucose, and Body Weight at Week 12 and at Final Visit (24-week study)

  GLUCOPHAGE
500 mg
Twice Daily
(n=67)
GLUCOPHAGE XR
1000 mg
Once Daily
(n=72)
1500 mg
Once Daily
(n=66)
Hemoglobin A1c (%)
  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 0.14a 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 12Weeks 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)
* All patients on GLUCOPHAGE 500 mg twice daily at Baseline
a n=68

After 12 weeks of treatment, there was an increase in mean HbA1c in all groups; in the GLUCOPHAGE XR 1000 mg group, the increase from baseline of 0.23% was statistically significant (see DOSAGE AND ADMINISTRATION).

Changes in lipid parameters in the previously described placebo-controlled dose-response study of GLUCOPHAGE XR are shown in Table 8.

Table 8: Summary of Mean Percent Changes from Baseline* in Major Lipid Variables at Final Visit (16-week study)

  GLUCOPHAGE XR Placebo
500 mg
Once Daily
1000 mg
Once Daily
1500 mg
Once Daily
2000 mg
Once Daily
1000 mg
Twice Daily
Total Cholesterol (mg/dL) (n=120) (n=113) (n=110) (n=126) (n=117) (n=110)
  Baseline 210.3 218.1 214.6 204.4 208.2 208.6
  Mean % Change at FINAL VISIT 1.0% 1.7% 0.7% –1.6% –2.6% 2.6%
Total Triglycerides (mg/dL) (n=120) (n=113) (n=110) (n=126) (n=117) (n=110)
  Baseline 220.2 211.9 198.0 194.2 179.0 211.7
  Mean % Change at FINAL VISIT 14.5% 9.4% 15.1% 14.9% 9.4% 10.9%
LDL-Cholesterol (mg/dL) (n=119) (n=113) (n=109) (n=126) (n=117) (n=107)
  Baseline 131.0 134.9 135.8 125.8 131.4 131.9
  Mean % Change at FINAL VISIT –1.4% –1.6% –3.5% –3.3% –5.5% 3.2%
HDL-Cholesterol (mg/dL) (n=120) (n=108) (n=108) (n=125) (n=117) (n=108)
  Baseline 40.8 41.6 40.6 40.2 42.4 39.4
  Mean % Change at FINAL VISIT 6.2% 8.6% 5.5% 6.1% 7.1% 5.8%
* 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.

Table 9: Summary of Mean Percent Changes from Baseline* in Major Lipid Variables at Final Visit (24-week study)

  GLUCOPHAGE GLUCOPHAGE XR
500 mg
Twice Daily
1000 mg
Once Daily
1500 mg
Once Daily
Total Cholesterol (mg/dL) (n=68) (n=70) (n=66)
  Baseline 199.0 201.9 201.6
  Mean % Change at FINAL VISIT 0.1% 1.3% 0.1%
Total Triglycerides (mg/dL) (n=68) (n=70) (n=66)
  Baseline 178.0 169.2 206.8
  Mean % Change at FINAL VISIT 6.3% 25.3% 33.4%
LDL-Cholesterol (mg/dL) (n=68) (n=70) (n=66)
  Baseline 122.1 126.2 115.7
  Mean % Change at FINAL VISIT -1.3% -3.3% -3.7%
HDL-Cholesterol (mg/dL) (n=68) (n=70) (n=65)
  Baseline 41.9 41.7 44.6
  Mean % Change at FINAL VISIT 4.8% 1.0% –2.1%
* 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).

Table 10: GLUCOPHAGE vs Placebo (Pediatricsa) Summary of Mean Changes from Baseline* in Plasma Glucose and Body Weight at Final Visit

  GLUCOPHAGE Placebo p-Value
FPG (mg/dL) (n=37) (n=36)  
  Baseline 162.4 192.3  
  Change at FINAL VISIT –42.9 21.4 < 0.001
Body Weight (lbs) (n=39) (n=38)  
  Baseline 205.3 189.0  
  Change at FINAL VISIT –3.3 –2.0 NS**
a Pediatric patients mean age 13.8 years (range10-16 years)
* All patients on diet therapy at Baseline
** Not statistically significant

Last reviewed on RxList: 12/6/2010
This monograph has been modified to include the generic and brand name in many instances.

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