Clinical study
Glycemic control with Glyburide/Metformin tablets in combination with rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial

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Abstract

Purpose

To assess the efficacy and safety of adding rosiglitazone to an established regimen of glyburide/metformin in patients with type 2 diabetes who had not achieved adequate glycemic control (glycosylated hemoglobin [HbA1C] levels >7.0% and ≤10.0%).

Methods

Following an open-label, lead-in phase to optimize the dosing of glyburide/metformin tablets, 365 patients randomly received additive therapy comprising rosiglitazone (4 mg once daily) or placebo for 24 weeks. Based on glycemic response, rosiglitazone dose was maintained or increased to 4 mg twice daily. Glyburide/metformin dose was maintained or reduced by 2.5/500 mg for symptomatic hypoglycemia. The primary endpoint was the change in HbA1C level from baseline to week 24. The proportions of patients achieving HbA1C levels <7% and a fasting plasma glucose level <126 mg/dL were also assessed.

Results

After 24 weeks, therapy with glyburide/metformin plus rosiglitazone resulted in a greater reduction in HbA1C levels (–1.0%, P <0.001) compared with combination therapy that included placebo, and in a larger proportion of patients (42% vs. 14%) who attained levels <7%. The difference in fasting plasma glucose levels between groups was –48 mg/dL (P <0.001), favoring glyburide/metformin plus rosiglitazone. The adverse event profile in the rosiglitazone-treated group included mild-to-moderate edema (8%), hypoglycemia (22%), and weight gain of 3 kg. No patient experienced hypoglycemia requiring third-party assistance.

Conclusion

In patients with inadequate glycemic control despite established glyburide/metformin therapy, the addition of rosiglitazone improves glycemic control, allowing more patients to achieve an HbA1C level <7% and perhaps delaying the need for insulin treatment.

Section snippets

Study sample

The study was carried out at 61 centers in the United States. All patients gave written informed consent before participating. Patients with inadequately controlled type 2 diabetes (glycosylated hemoglobin [HbA1C] levels >7.0% and ≤10.0%) were enrolled if they were between 20 and 78 years of age and had a body mass index between 23 and 40 kg/m2 (inclusive). All patients were on a stable regimen with an oral antidiabetic agent for 8 weeks before screening. For the lead-in phase, the inclusion

Results

Of the 453 patients enrolled, 365 who were receiving stable doses of glyburide/metformin were assigned randomly to 24 weeks of double-blind treatment with either rosiglitazone (n = 181) or placebo (n = 184) (Figure 1). Forty-four of the 88 patients who were excluded during the lead-in phase did not meet randomization criteria. A total of 261 patients (72%) completed the 24-week study.

The mean (±SD) age of the 365 randomly assigned patients was 57 ± 9 years (Table 1). Most were white (74% [n =

Discussion

Because type 2 diabetes is a chronic and progressive disease, most patients eventually require a combination pharmacologic approach to achieve or maintain glycemic control (2). In the earlier stages of disease when monotherapy fails, the combination of two or three oral agents may suffice; if glycemic control still cannot be achieved, insulin therapy may be required 1, 5. Addition of metformin to a failed sulfonylurea monotherapy regimen, or vice versa, often improves glucose control. Further

Acknowledgements

The contributions of the patients and the clinic staff to the success of this study are greatly appreciated.

References (14)

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This study was supported by a grant from the Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey. Dr. Dailey has received grant support from Bristol-Myers Squibb and has served on its Speakers Bureau and as an occasional consultant.

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