A PROSPECTIVE TRIAL OF RISK-FACTORS FOR SULFONYLUREA-INDUCED HYPOGLYCEMIA IN TYPE-2 DIABETES-MELLITUS

Context.-Retrospective studies have identified oral sulfonylureas, age , and fasting as major risk factors for hypoglycemia in patients with type 2 diabetes. Sulfonylureas may be withheld from elderly patients o ut of concern for hypoglycemia. Objective.-To evaluate the hypoglycemi c effects of maximum doses of once-daily second-generation sulfonylure as administered to fasting elderly patients. Design.-A prospective, ra ndomized, double-blind clinical trial. Setting.-The University of New Mexico General Clinical Research Center. Patients.-Fifty-two sulfonylu rea-treated subjects with type 2 diabetes with a mean (SD) age of 65.1 (5.7) years. Interventions.-Subjects were randomly assigned to glybur ide or glipizide gastrointestinal therapeutic system (GITS). Each subj ect participated in three 23-hour fasting studies after the sequential administration of 1 week of placebo and 1 week of 10 mg and 1 week of 20 mg of the assigned sulfonylurea. Main Outcome Measures.-Occurrence of hypoglycemia (defined as plasma glucose level <3.33 mmol/L [60 mg/ dL]) and hormonal parameters during the final 9 hours of the 23-hour f ast in patients who had taken sulfonylureas vs placebo. Results.-No hy poglycemia was observed during 156 fasting studies. Plasma glucose lev el was decreased (nadir, 4.9 mmol/L [88 mg/dL] for a 20-mg dose of gly buride vs 8.3 mmol/L [150 mg/dL] for placebo; nadir, 5.8 mmol/L [105 m g/dL] for a 20-mg dose of glipizide GITS vs 8.7 mmol/L [157 mg/dL] for placebo), and serum insulin was increased in the sulfonylurea studies compared with placebo (P<.001). Plasma glucose parameters did not dif fer between the 2 sulfonylureas, but C peptide concentrations were inc reased in the glyburide group compared with glipizide GITS in the 20-m g study (P=.05). Concentrations of epinephrine were increased in the s ulfonylurea studies compared with placebo (P<.001). Epinephrine secret ion increased when glucose concentration fell below the mean (SD) leve l of 9.10 (2.66) mmol/L (164 [48] mg/dL) in the 10-mg study and 8.77 ( 2.83) mmol/L (158 [51] mg/dL) in the 20-mg study. Conclusions.-Fasting was well tolerated among these elderly patients with type 2 diabetes treated with sulfonylureas. Older age should not be considered a contr aindication to sulfonylurea treatment for diabetes. Stimulation of epi nephrine secretion at normal or elevated plasma glucose levels appears to be the primary mechanism of protection against hypoglycemia in thi s study.