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What Is the Benefit of Increasing the Sulfonylurea Dose?

Svante Stenman, MD; Arne Melander, MD; Per-Henrik Groop, MD; and Leif C. Groop, MD
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From Helsinki University Central Hospital, Helsinki, Finland; the University of Lund, Malmo, Sweden. Requests for Reprints: Svante Stenman, MD, IV Department of Medicine, Helsinki University Central Hospital, 00170 Helsinki, Finland. Acknowledgments: The authors thank Ms. Kirsi Laakkonen and Mr. Esa Laurila for technical and nursing work in the study. Grant Support: By Pfizer Roerig New York, New York, and by the Sigrid Juselius Foundation and Finska Lakaresallskapet, Helsinki, Finland.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1993;118(3):169-172. doi:10.7326/0003-4819-118-3-199302010-00002
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Objective: To study the clinical benefit of increasing the dose of the sulfonylurea, glipizide, from 10 to 40 mg per day.

Design: A placebo-controlled, double-blind, cross-over study.

Setting: An outpatient clinic at the Helsinki University Hospital, Finland.

Patients: Twenty-three patients with non–insulin-dependent diabetes mellitus.

Methods: Patients were given glipizide in three different dose schedules for 3 months each: 10 mg in the morning or 10 mg or 20 mg in the morning and the evening. Glycemic control was followed by HbA1c measurements and blood glucose monitoring at home. Beta cell function was assessed by measuring insulin responses to a test meal.

Results: Mean home-monitored blood glucose was 12.4 mmol/L during placebo treatment, and it was 9.6, 9.2, and 8.9 mmol/L after treatment with glipizide, 10, 20, or 40 mg, respectively. The levels of blood glucose and HbA1c differed after all treatment groups from placebo (P < 0.001) but not among themselves. The insulin response to a test meal was greatest after 10 mg of glipizide and weakest after 40 mg/d (P = 0.02 compared with the 10-mg dose). All treatments stimulated insulin secretion more than placebo (P < 0.001).

Conclusions: Increasing the glipizide dose to more than 10 mg once daily produces little or no benefit and may reduce β-cell function.


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Figure 1.
Average home-monitored blood glucose.

Values were measured before breakfast, lunch and dinner and at bedtime. n.s. = not significant.

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Figure 2.
Glucose and insulin response curve to a test meal.Table 2.

The glipizide amount given 30 minutes before the test meal was 10 mg after treatment with 10 and 20 mg/d and 20 mg after 40 mg/d (———0 mg; – · – 10 mg; — — — 20 mg; – – – – 40 mg). Each symbol represents the mean of 23 patients. For statistical comparisons, see .

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