Glyburide and Metformin Hydrochloride Tablets

In double-blind clinical trials involving Glyburide and Metformin Hydrochloride Tablets as initial therapy or as second-line therapy, a total of 642 patients received Glyburide and Metformin Hydrochloride Tablets, 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 Hydrochloride Tablets (all strengths) as initial therapy and second-line therapy are listed in Table 6. 

In a controlled clinical trial of rosiglitazone versus placebo in patients treated with Glyburide and Metformin Hydrochloride Tablets (n=365), 181 patients received Glyburide and Metformin Hydrochloride Tablets with rosiglitazone and 184 received Glyburide and Metformin Hydrochloride Tablets 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 Hydrochloride Tablets 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 Hydrochloride Tablets are summarized in Table 7. The frequency of hypoglycemic symptoms in patients treated with Glyburide and Metformin Hydrochloride Tablets 1.25 mg/250 mg was highest in patients with a baseline HbA 1c <7%, lower in those with a baseline HbA 1c of between 7% and 8%, and was comparable to placebo and metformin in those with a baseline HbA 1c >8%. For patients with a baseline HbA 1c between 8% and 11% treated with Glyburide and Metformin Hydrochloride Tablets 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 Hydrochloride Tablets experienced hypoglycemic symptoms. When rosiglitazone was added to Glyburide and Metformin Hydrochloride Tablets 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 Glyburide and Metformin Hydrochloride Tablets Therapy.) 

Gastrointestinal Reactions 

The incidence of gastrointestinal (GI) side effects (diarrhea, nausea/vomiting, and abdominal pain) in the initial therapy trial are summarized in Table 7. Across all Glyburide and Metformin Hydrochloride Tablets trials, GI symptoms were the most common adverse events with Glyburide and Metformin Hydrochloride Tablets and were more frequent at higher dose levels. In controlled trials, <2% of patients discontinued Glyburide and Metformin Hydrochloride Tablets therapy due to GI adverse events. 

In postmarketing reports cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; Glyburide and Metformin Hydrochloride Tablets should be discontinued if this occurs.