ADVERSE REACTIONS
GLUCOVANCE
In double-blind clinical trials involving GLUCOVANCE as initial therapy or as second-line therapy, a total of 642 patients received GLUCOVANCE, 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 GLUCOVANCE (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 GLUCOVANCE Used as Initial or Second-Line Therapy
Adverse Event |
|---|
| Number (%) of Patients |
|---|
| Placebo
N=161 | Glyburide
N=324 | Metformin
N=312 | GLUCOVANCE
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 (17.0) |
| 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 (8.0) | 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 GLUCOVANCE (n=365), 181 patients received GLUCOVANCE with rosiglitazone and 184 received GLUCOVANCE 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 GLUCOVANCE 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 GLUCOVANCE are summarized in Table 7. The frequency of hypoglycemic symptoms in patients treated with GLUCOVANCE 1.25 mg/250 mg was highest in patients with a baseline HbA1c<7%, lower in those with a baseline HbA1c of between 7% and 8%, and was comparable to placebo and metformin in those with a baseline HbA1c>8%. For patients with a baseline HbA1c between 8% and 11% treated with GLUCOVANCE 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 GLUCOVANCE experienced hypoglycemic symptoms. When rosiglitazone was added to GLUCOVANCE 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 PRECAUTIONS: General: Addition of Thiazolidinediones to GLUCOVANCE Therapy.)
Gastrointestinal Reactions
The incidence of GI side effects (diarrhea, nausea/vomiting, and abdominal pain) in the initial therapy trial are summarized in Table 7. Across all GLUCOVANCE trials, GI symptoms were the most common adverse events with GLUCOVANCE and were more frequent at higher dose levels. In controlled trials, <2% of patients discontinued GLUCOVANCE therapy due to GI adverse events.
Table 7: Treatment Emergent Symptoms of Hypoglycemia or Gastrointestinal Adverse Events in a Placebo- and Active-Controlled Trial of GLUCOVANCE as Initial Therapy | Variable | Placebo
N=161 | Glyburide
Tablets
N=160 | Metformin
Tablets
N=159 | GLUCOVANCE
1.25 mg/250 mg
Tablets
N=158 | GLUCOVANCE
2.5 mg/500 mg
Tablets
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) |
|
