Comprehensive Evaluation of Combination Therapy with Basal Insulin and Either Lixisenatide or Vildagliptin in Japanese Patients with Type 2 Diabetes: A Randomized, Open-Label, Parallel-Group, Multicenter Study.

INTRODUCTION: We comprehensively evaluated the effects of combination therapy with insulin glargine and the incretin-based drugs lixisenatide or vildagliptin in Japanese patients with type 2 diabetes. METHODS: In this 12-week, randomized, open-label, parallel-group, multicenter study (GLP-ONE Kobe), the incretin-based drug sitagliptin was randomly switched to lixisenatide (20 µg/day, n = 18) or vildagliptin (100 mg/day, n = 20) in patients with inadequate glycemic control despite combination therapy with insulin glargine and sitagliptin. The dose of insulin glargine was titrated after the switch to maintain fasting blood glucose at approximately 110 mg/dL. The primary end points of the study were the change in glycosylated hemoglobin (HbA1c) level between before and 12 weeks after the treatment switch, the proportion of patients achieving an HbA1c level below 7.0%, and the postprandial increase in glucose concentration as assessed by self-monitoring of blood glucose. RESULTS: The change in HbA1c level from baseline to 12 weeks did not differ significantly between the lixisenatide and vildagliptin groups (- 0.6 ± 0.7% and - 0.6 ± 1.2%, respectively, P = 0.920). Neither the proportion of patients achieving an HbA1c level below 7.0% nor the postprandial increase in glucose concentration was different between two groups. Body weight and serum low density lipoprotein (LDL) cholesterol level decreased significantly in the lixisenatide and vildagliptin groups, respectively. Both drugs were associated with mild gastrointestinal symptoms but not with severe hypoglycemia. Vildagliptin was associated with elevation of serum aspartate transaminase. Treatment satisfaction as assessed with the Diabetes Treatment Satisfaction Questionnaire did not differ significantly between the two groups. CONCLUSION: The combinations of basal insulin and either lixisenatide or vildagliptin have similar efficacies with regard to improvement of glycemic control. TRIAL REGISTRATION: This trial has been registered with UMIN (No. 000010769).

A case of primary aldosteronism caused by multiple adrenocortical macronodules.

A 60-year-old man presented with drug-resistant hypertension with hypokalemia, a high plasma aldosterone concentration (PAC) and suppressed plasma rennin activity (PRA). Imaging examinations showed multiple macronodules in the left adrenal gland. Endocrinological findings demonstrated autonomous aldosterone secretion and (131)I-adosterol scintigraphy demonstrated a left sided uptake. Laparoscopic left adrenalectomy normalized serum potassium levels and PAC, and substantially improved hypertension. Pathological and immunohistochemical analysis demonstrated that these nodules were positive for 3ß-hydroxysteroid dehydrogenase (HSD3B) but not for CYP17. In addition, zona glomerulosa demonstrated "paradoxical hyperplasia", in which these cells were negative for HSD3B. All of these data indicated that the nodules in the left adrenal gland were mainly responsible for the autonomous aldosterone secretion. We conclude that the primary aldosteronism in this case was caused by multiple macronodules. This is a very rare case of primary aldosteronism caused by multiple adrenocortical macronodules.