Multicenter, randomized, double-masked, parallel-group assessment of simultaneous glipizide/metformin as second-line pharmacologic treatment for patients with type 2 diabetes mellitus that is inadequately controlled by a sulfonylurea.

Background: Many patients with type 2 diabetes mellitus (DM) with inadequate long-term blood glucose control with sulfonylurea or metformin monotherapy require additional treatment. The synergistic effects of combining glipizide with metformin on glucose control may be realized by treating the primary effects of type 2 DM, impaired insulin secretion, and insulin resistance.

Objective: This study assessed therapy with glipizide/metformin combination tablets in patients with type 2 DM that is uncontrolled by at least half the maximum labeled daily dose of a sulfonylurea.

Methods: In this multicenter, double-masked, parallel-group, active-controlled study, patients were randomized to receive glipizide 30-mg, metformin 500-mg, or glipizide/metformin 5/500 mg tablets for 18 weeks (metformin and glipizide/metformin doses were titrated to achieve blood glucose control). Maximum total daily doses were glipizide 30 mg, metformin 2000 mg, and glipizide/ metformin 20/2000 mg.

Results: A total of 247 patients were included in the study. The mean (SD) age was 56.2 (10.1) years; 61.5% of patients were male; 70.0% were white, 15.8% were Hispanic/Latino, 13.0% were black, and 1.2% were Asian/Pacific Islanders. Patients were, on average, obese (mean [SD] body mass index, 31.3 [4.7] kg/m2), had moderate to severe hyperglycemia (mean [SD] glycated hemoglobin [HbA1c], 8.7% [1.1]), and had a mean (SD) DM duration of 6.5 (4.9) years. Glipizide/ metformin tablets controlled the HbA1c level more effectively than did either glipizide or metformin monotherapies (mean treatment differences, in favor of glipizide/ metformin, of -1.06% and -0.98%, respectively, P < 0.001). At study end, an HbA1c level < 7.0% was achieved in approximately 4-fold more patients who were treated with glipizide/metformin (36.3%) compared with glipizide (8.9%) or metformin (9.9%) monotherapies. Glipizide/metformin tablets also reduced the fasting plasma glucose (FPG) level and the 3-hour postprandial glucose area under the concentration-time curve more effectively than did either monotherapy, without increasing the fasting insulin level. The greater blood glucose control with glipizide/ metformin tablets was achieved at a mean daily dose of glipizide/metformin 17.5/1747 mg, compared with mean doses of glipizide 30.0 mg or metformin 1927 mg. Treatments were well tolerated, with a low incidence of symptoms of hypoglycemia evidenced by a fingerstick blood glucose measurement < or = 50 mg/dL in the combination group (12.6%); 1 patient discontinued the study treatment for this reason. No patient required medical assistance for hypoglycemia.

Conclusions: Glipizide/metformin tablets were more effective than either glipizide or metformin monotherapy in controlling HbA1c and in reducing FPG compared with baseline in patients with blood glucose that was uncontrolled with previous sulfonylurea treatment. In addition, patients receiving glipizide/ metformin were more likely to achieve an HbA1c level < 7.0%. These results were consistent with the synergistic effects on insulin resistance and beta cell dysfunction. Glipizide/metformin was well tolerated, with a low incidence of hypoglycemia.