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To the Editor: We published a study demonstrating that the hypoglycemic effect of maximal doses of once-daily second-generation sulfonylureas is minimal when administered to elderly subjects with type 2 diabetes during a prolonged fast.¹ However, the issue of whether immediate-release sulfonylureas have increased hypoglycemic potential during such a fast remains controversial. Because comparative studies have shown that fasting and postprandial serum insulin concentrations are increased following immediate-release glipizide administration compared with glipizide gastrointestinal therapeutic system (GITS) administration, we investigated whether the risk of hypoglycemia is increased in elderly patients with type 2 diabetes taking immediate-release glipizide compared with glipizide GITS during a prolonged fast.²

Methods.
Twenty-six subjects with type 2 diabetes treated with sulfonylureas who participated in our previous study were enrolled using previously described inclusion and exclusion criteria.¹ All participants gave informed consent for the protocol as previously described.

On enrollment, study participants received immediate-release glipizide (20 mg daily: 15 mg in the morning and 5 mg in the evening) for at least 1 week prior to the study. Subjects were subsequently admitted to the University of New Mexico General Clinical Research Center for a 23-hour fasting study. Subjects were fed a 33.5 kJ/kg (8 kcal/kg) American Diabetes Association meal at 6 PM on the evening prior to study. At 8 AM the following morning, subjects ingested 20 mg of immediate-release glipizide plasma glucose, and insulin levels were determined at baseline (7:50 AM and 8 AM) and then every 30 minutes during the final 9 hours of the 23-hour fast. Results were compared with plasma glucose and insulin concentrations obtained during the 20-mg glipizide GITS arm of the previous study using repeated measures analysis of variance.¹ Hypoglycemia was defined as a plasma glucose concentration less than 3.33 mmol/L (59.4 mg/dL) with typical hypoglycemic symptoms or any plasma glucose concentration less than 2.78 mmol/L (50.1 mg/dL).

Results.
The subjects consisted of 21 men and 5 women with a mean (SD) age of 65 (6) years, a mean (SD) body mass index (BMI) of 27.9 (4.6) kg/m², a mean (SD) duration of diabetes of 8.5 (7.7) years, and a mean (SD) glycosylated hemoglobin concentration of 0.088 (0.017) (reference range = 0.040-0.068). Mean plasma glucose concentrations for both formulations of glipizide are shown in Figure 1, top. Mean (SD) baseline values did not significantly differ between glipizide GITS and immediate-release glipizide (9.7 [3.3] vs 10.6 [2.6] mmol/L [174.7 {59.4} vs 190.9 {46.8} mg/dL], respectively, P>.05), nor did nadir plasma glucose concentrations (5.8 [2.4] vs 5.9 [1.8] mmol/L [104.5 {43.2} vs 106.3 {32.4} mg/dL], P>.05). No subjects developed symptomatic hypoglycemia during the studies. Mean serum insulin concentrations did not significantly differ between glipizide GITS and immediate-release glipizide (P>.05) (Figure 1, bottom).

View larger version (22K): [in this window] [in a new window] Figure. Mean Plasma Glucose and Total Serum Insulin Concentrations During the Final 9 Hours of a 23-Hour Fast Among Elderly Subjects With Type 2 Diabetes GITS indicates glipizide gastrointestinal therapeutic system. Data points indicate mean±SD. To convert glucose values to milligrams per deciliter, divide by 0.05551.

Comment.
Our results demonstrate that hypoglycemia did not occur in otherwise healthy older patients with type 2 diabetes receiving immediate-release glipizide during a short-term fast. Furthermore, the glucose and insulin profiles elicited by immediate-release glipizide and glipizide GITS were similar under conditions of a 23-hour fast, suggesting that meal ingestion may be necessary to demonstrate the differing pharmacologic activities of these agents. These data suggest that immediate-release glipizide can be administered to healthy older patients with type 2 diabetes during a short-term fast without a significant risk of serious hypoglycemia.

AUTHOR INFORMATION
Funding/Support: This research was supported by a grant from Pfizer Inc, New York, NY, and by the University of New Mexico Clinical Research Center (NIH NCRR GCRC grant 5M01-RR00997).

Mark R. Burge, MD; Kristen Schmitz-Fiorentino, MD; Vidushi Sood, MD; David S. Schade, MD
University of New Mexico School of Medicine
Albuquerque

1. Burge MR, Schmitz-Fiorentino K, Fischette C, Qualls CR, Schade DS. A prospective trial of risk factors for sulfonylurea-induced hypoglycemia in type 2 diabetes mellitus. JAMA. 1998;279:137-143. FREE FULL TEXT 2. Berelowitz M, Fischette C, Cefalu W, Schade DS, Sutfin T, Kourides IA. Comparative efficacy of a once-daily controlled release formulation of glipizide and immediate release glipizide in patients with NIDDM. Diabetes Care. 1994;17:1460-1464. ABSTRACT

Edited by Margaret A. Winker, MD, Deputy Editor, and Phil B. Fontanarosa, MD, Interim Coeditor.

JAMA. 1999;281:1084-1085.

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