Effect of adding a sulfonylurea in patients with non-insulin-dependent diabetes mellitus previously well controlled with insulin.

OBJECTIVE: To determine whether insulin-requiring patients with non-insulin-dependent diabetes mellitus (NIDDM) and good glycemic control would benefit in weight control, serum lipid concentrations, or blood pressure from a reduction in exogenous insulin treatment. METHODS: Eighteen patients with well-controlled NIDDM who required insulin therapy were entered into a randomized, placebo-controlled, double-blind, crossover study of the addition for 12 weeks of treatment with a second-generation sulfonylurea agent (micronized glyburide). RESULTS: The mean fasting plasma glucose at entry was 7.00 +/- 0.22 mmol/L and at the end of the 12-week treatment phase was 7.67 +/- 0.39 mmol/L with placebo and 7.28 +/- 0.44 mmol/L with active drug. Hemoglobin A(1c) was unchanged during the study (7.5 +/- 0.2% at entry, 7.5 +/- 0.3% with placebo, and 7.4 +/- 0.3% with active drug). Addition of the orally administered agent resulted in a 29% decrease in exogenous insulin requirements and a 37% increase in 24-hour urinary C-peptide excretion. Patients had no change in weight after 12 weeks of either placebo or active drug. Plasma cholesterol levels declined slightly during the study, but they did not differ significantly during drug and placebo treatment. Blood pressure was unchanged in both the subjects with and without hypertension. CONCLUSION: In patients with NIDDM and good glycemic control with insulin treatment, a glyburide-related increase in endogenous insulin secretion caused a proportionate decrease in exogenous insulin requirements. With continued good glycemic control, however, the orally administered agent showed no additional benefit on weight, blood pressure, plasma triglycerides, or low-density lipoprotein or high-density lipoprotein cholesterol.

Efficacy and safety of reformulated, micronized glyburide tablets in patients with non-insulin-dependent diabetes mellitus: a multicenter, double-blind, randomized trial.

The subjects were 206 patients (123 men, 83 women) with non-insulin-dependent diabetes mellitus, aged 33 to 80 years. For at least 4 weeks prior to the study each subject had been taking 5-mg tablets of original, nonmicronized glyburide (Micronase tablets) in doses of 5, 10, 15, or 20 mg daily. In a double-blind 12-week study, the subjects were randomly assigned to continue receiving 5-mg tablets of original glyburide or to substitute 3-mg tablets of reformulated, micronized glyburide (Glynase PresTab tablets) for the original tablets. Glyburide tablets had been reformulated to improve their bioavailability. Baseline mean fasting serum glucose levels in the groups taking reformulated and original glyburide were 169.3 and 168.3 mg/dl, respectively; at study end point, their respective serum glucose levels were 186.0 and 177.0 mg/dl. The differences between groups were not significant; in both groups, however, end point glucose levels were significantly higher than baseline levels. Baseline hemoglobin A1C levels in the groups taking reformulated and original glyburide were both 7.6%; at study end point, hemoglobin A1C levels had improved slightly in each group to 7.4% and 7.5%, respectively. The differences between and within groups at end point were not significant. No between-group differences at baseline or at end point were found in mean levels of postprandial serum glucose, fasting C-peptide, or postprandial C-peptide. Medical events experienced by the subjects in the two groups were similar in nature and number. Changes in other laboratory test results, vital signs, and weight were not clinically meaningful.(ABSTRACT TRUNCATED AT 250 WORDS)

Unaltered drug metabolizing enzyme systems in type II diabetes mellitus before and during glyburide therapy.

Diabetes mellitus is associated with alterations in hepatic drug metabolizing enzyme activities in experimental animals. To determine whether Type II diabetes or glyburide affect hepatic drug metabolism, the authors used 13C-labeled aminopyrine and caffeine breath tests as in vivo probes of the hepatic cytochrome P450 and P(1)450 enzyme activities respectively in six subjects with Type II diabetes (4 women, 2 men). These subjects had been treated previously with diet, had an age range of 41-63 years, had a body mass index range of 24.1-43.3 kg/m2 and had a mean fasting plasma glucose of 14.6 +/- 1.2 mM and a mean hemoglobin A1c of 12.2 +/- 0.7%. These subjects did not drink alcohol or take drugs known to affect hepatic drug metabolism. The caffeine and aminopyrine breath tests (CBT, ABT) were performed sequentially while fasting before the start of glyburide treatment (5 mg daily) and at weekly intervals for 4 weeks. ABT and CBT values are expressed as cumulative percentage of dose exhaled through 2 hours. Before beginning glyburide, the mean ABT and CBT results were 10.2 +/- 0.7% and 4.2 +/- 0.7% respectively, well within the normal ranges for these tests (ABT 6.5-15%; CBT 2.5-10%). The ABT and CBT values remained unaltered during 4 weeks of glyburide therapy. However, FBS decreased to 10.2 +/- 1.1 mM and HbA1C to 10.1 +/- 0.8% by the end of drug treatment. Type II diabetes that is poorly controlled by diet alone is not associated with alterations of the hepatic drug metabolizing enzymes as judged by the caffeine and aminopyrine breath tests. Furthermore, glyburide does not induce or inhibit the drug metabolizing enzyme systems in the liver, thereby precluding drug-drug interactions of this type.