OBJECTIVE -A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise.RESEARCH DESIGN AND METHODS -Enrolled patients (n ϭ 150) had received treatment with diet and exercise in the previous 3 months with HbA 1c Ͼ7 and Յ12%. Patients were randomized to receive monotherapy with repaglinide (n ϭ 76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n ϭ 74) (60 mg/meal, maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points were changes in HbA 1c and fasting plasma glucose (FPG) values from baseline, respectively. Postprandial glucose, insulin, and glucagon were assessed after a liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse events or hypoglycemia. RESULTS -Mean baselineHbA 1c values were similar in both groups (8.9%). Final HbA 1c values were lower for repaglinide monotherapy than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA 1c were significantly greater for repaglinide monotherapy than nateglinide monotherapy (Ϫ1.57 vs. Ϫ1.04%; P ϭ 0.002). Mean changes in FPG also demonstrated significantly greater efficacy for repaglinide than nateglinide (Ϫ57 vs. Ϫ18 mg/dl; P Ͻ 0.001). HbA 1c values Ͻ7% were achieved by 54% of repaglinide-treated patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated with repaglinide (five subjects with one episode each) who had minor hypoglycemic episodes (blood glucose Ͻ50 mg/dl) versus 0 patients for nateglinide. Mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group.CONCLUSIONS -In patients previously treated with diet and exercise, repaglinide and nateglinide had similar postprandial glycemic effects, but repaglinide monotherapy was significantly more effective than nateglinide monotherapy in reducing HbA 1c and FPG values after 16 weeks of therapy. Diabetes Care 27:1265-1270, 2004R epaglinide (Prandin) and nateglinide (Starlix) are short-acting insulin secretagogues that are approved for the treatment of type 2 diabetes (1,2). Both of these agents have relatively short elimination half-lives (1 h for repaglinide and 1.5 h for nateglinide). When administered at mealtimes, both agents produce peak insulin stimulation during the postprandial period, when physiological insulin needs are maximal. Clinical trials have demonstrated that both agents increase insulin response to postprandial glucose, resulting in reductions of HbA 1c and fasting plasma glucose (FPG) levels.Although both repaglinide and nateglinide stimulate insulin secretion by inhibition of the ATP-dependent potassium channels of ␤-cells, the molecular binding site of repaglinide is different from that of nateglinide and sulfonylureas (3-5). Clinical trial comparisons of repaglinide versus sulfonylurea mono...

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Although 123I-MIBG has been in clinical use for the imaging of pheochromocytoma for many years, a large multicenter evaluation of this agent has never been performed. The present study was designed to provide a prospective confirmation of the performance of 123I-MIBG scintigraphy for the evaluation of patients with known or suspected primary or metastatic pheochromocytoma or paraganglioma. Methods A total of 81 patients with a prior history of primary or metastatic pheochromocytoma or paraganglioma and 69 with suspected pheochromocytoma or paraganglioma based on symptoms of catecholamine excess, CT or MRI findings, or elevated catecholamine or metanephrine levels underwent whole-body planar and selected SPECT 24 h after the administration of 123I-MIBG. Images were independently interpreted by 3 masked readers, with consensus requiring agreement of at least 2 readers. Final diagnoses were based on histopathology, correlative imaging, catecholamine or metanephrine measurements, and clinical follow-up. Results Among 140 patients with definitive diagnoses (91, disease present; 49, disease absent), 123I-MIBG planar scintigraphy had a sensitivity and specificity of 82%. For patients evaluated for suspected disease, sensitivity and specificity were 88% and 84%, respectively. For the subpopulations of adrenal (pheochromocytoma) and extraadrenal (paraganglioma) tumors, sensitivities were 88% and 67%, respectively. The addition of SPECT increased reader confidence but minimally affected sensitivity and specificity. Conclusion This prospective study demonstrated a sensitivity of 82%–88% and specificity of 82%–84% for 123I-MIBG imaging used in the diagnostic assessment of primary or metastatic pheochromocytoma or paraganglioma.

This prospective multicenter trial of (123)I-mIBG scintigraphy documents high sensitivity and specificity of this imaging technique in patients with both newly diagnosed and previously treated neuroblastoma.

OBJECTIVE -An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes. RESEARCH DESIGN AND METHODS -Enrolled patients (n ϭ 192) had HbA 1cϾ7% and Յ12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide Յ2.5 mg, metformin Յ500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n ϭ 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n ϭ 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16. RESULTS -FinalHbA 1c values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA 1c (-1.28 vs. -0.67%; P Ͻ 0.001) and of fasting plasma glucose (FPG) (-39 vs. -21 mg/dl; P ϭ 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 A.M. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens. By reducing postprandial blood glucose peaks, these drugs lower 24-h blood glucose profiles and reduce HbA 1c levels. Both agents stimulate insulin secretion via closure of ATP-dependent potassium channels (K ATP channels) of the outer membrane of ␤-cells (1-3). The molecular binding sites of the two drugs are not identical (4). CONCLUSIONSTo date, no clinical trial has compared the efficacy and safety of repaglinide and nateglinide in a "head-to-head" design. In a combination therapy trial of up to 5 months of treatment with repaglinide plus metformin, reductions of HbA 1c values were much greater for the combination than the respective monotherapies; in the patients who had previously failed to show adequate glycemic control using metformin alone (HbA 1c Ͼ 7.0%), reductions of HbA 1c values were 1.1% greater than in those who continued metformin monotherapy (5). A comparable study of 24-week treatment using nateglinide plus metformin reported a reduction of HbA 1c levels by up to 0.6% compared with metformin monotherapy (6). Both of these studies collected data in patients who had earlier shown unsatisfactory response to metformin, and metformin treatment was continued up to randomization to the combination treatments.Preclinical research has indicated that nateglinide may have capabilities of stimulating certain glucose-elevating hormones (glucagon, growth hormone) that are not stimulated by repaglinide (7,8). Such drug actions could potentially reduce the effic...