ADVERSE REACTIONS
Glyburide and Metformin
In double-blind clinical trials involving glyburide and metformin as initial therapy or as second-line therapy, a total of 642 patients received glyburide and metformin, 312 received metformin therapy, 324 received glyburide therapy, and 161 received placebo. The percent of patients reporting events and types of adverse events reported in clinical trials of glyburide and metformin (all strengths) as initial therapy and second-line therapy are listed in.
Table 6
Table 6: Most Common Clinical Adverse Events (> 5 Percent) in Double-Blind Clinical Studies of Glyburide and Metformin Used as Initial or Second-Line Therapy
Adverse Event
|
Number (%) of Patients
|
Placebo
N
= 161
|
Glyburide N
=
324
|
Metformin N
=
312
|
Glyburide and
Metformin N
= 642
|
Upper respiratory infection |
22 (13.7) |
57 (17.6) |
51 (16.3) |
111 (17.3) |
Diarrhea |
9 (5.6) |
20 (6.2) |
64 (20.5) |
109 (17) |
Headache |
17 (10.6) |
37 (11.4) |
29 (9.3) |
57 (8.9) |
Nausea/vomiting |
10 (6.2) |
17 (5.2) |
38 (12.2) |
49 (7.6) |
Abdominal pain |
6 (3.7) |
10 (3.1) |
25 (8) |
44 (6.9) |
Dizziness |
7 (4.3) |
18 (5.6) |
12 (3.8) |
35 (5.5) |
In a controlled clinical trial of rosiglitazone versus placebo in patients treated with glyburide and metformin (n = 365), 181 patients received glyburide and metformin with rosiglitazone and 184 received glyburide and metformin with placebo.
Edema was reported in 7.7% (14/181) of patients treated with rosiglitazone compared to 2.2% (4/184) of patients treated with placebo. A mean weight gain of 3 kg was observed in rosiglitazone-treated patients.
Disulfiram-like reactions have very rarely been reported in patients treated with glyburide tablets.
Hypoglycemia
In controlled clinical trials of glyburide and metformin there were no hypoglycemic episodes requiring medical intervention and/or pharmacologic therapy; all events were managed by the patients. The incidence of reported symptoms of hypoglycemia (such as dizziness, shakiness, sweating, and hunger), in the initial therapy trial of glyburide and metformin are summarized in.
Table 7
The frequency of hypoglycemic symptoms in patients treated with glyburide and metformin 1.25 mg/250 mg was highest in patients with a baseline HbA < 7%, lower in those with a baseline HbA of between 7% and 8%, and was comparable to placebo and metformin in those with a baseline HbA > 8%. For patients with a baseline HbA between 8% and 11% treated with glyburide and metformin 2.5 mg/500 mg as initial therapy, the frequency of hypoglycemic symptoms was 30 to 35%. As second-line therapy in patients inadequately controlled on sulfonylurea alone, approximately 6.8% of all patients treated with glyburide and metformin experienced hypoglycemic symptoms. When rosiglitazone was added to glyburide and metformin therapy, 22% of patients reported one or more fingerstick glucose measurements ≤ 50 mg/dL compared to 3.3% of placebo-treated patients. All hypoglycemic events were managed by the patients and only one patient discontinued for hypoglycemia (see, ,).
1c
1c
1c
1c
PRECAUTIONS
General
Addition of Thiazolidinediones to Glyburide and Metformin Therapy
Gastrointestinal Reactions
The incidence of gastrointestinal (GI) side effects (diarrhea, nausea/vomiting, and abdominal pain) in the initial therapy trial are summarized in. Across all glyburide and metformin trials, GI symptoms were the most common adverse events with glyburide and metformin and were more frequent at higher dose levels. In controlled trials, < 2% of patients discontinued glyburide and metformin therapy due to GI adverse events.
Table 7
Table 7: Treatment Emergent Symptoms of Hypoglycemia or Gastrointestinal Adverse Events in a Placebo- and Active-Controlled Trial of Glyburide and Metformin as Initial Therapy
Variable
|
Placebo
|
Glyburide
Tablets
|
Metformin
Tablets
|
Glyburide and
Metformin
1.25 mg/250 mg
Tablets
|
Glyburide and
Metformin
2.5 mg/500 mg Tablets
|
N = 161
|
N = 160
|
N = 159
|
N = 158
|
N = 162
|
Mean Final Dose |
0 mg |
5.3 mg |
1317 mg |
2.78 mg/557 mg |
4.1 mg/824 mg |
Number (%) of patients with symptoms of hypoglycemia |
5 (3.1) |
34 (21.3) |
5 (3.1) |
18 (11.4) |
61 (37.7) |
Number (%) of patients with gastrointestinal adverse events |
39 (24.2) |
38 (23.8) |
69 (43.3) |
50 (31.6) |
62 (38.3) |
In postmarketing reports cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; glyburide and metformin should be discontinued if this occurs.
|