Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.

BACKGROUND: VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. METHODS: Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. RESULTS: Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. CONCLUSIONS: In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

A Randomized Pilot Study of the Effect of Trelagliptin and Alogliptin on Glycemic Variability in Patients with Type 2 Diabetes.

INTRODUCTION: This open-label, parallel-group, exploratory study examined the effects of two dipeptidyl peptidase 4 (DPP4) inhibitors on glycemic variability (GV) in patients with type 2 diabetes. METHODS: Randomized patients with glycated hemoglobin A1c of at least 6.5% to less than 8.5% received trelagliptin 100 mg (n = 13) once weekly or alogliptin 25 mg (n = 14) once daily for 29 days. Continuous glucose monitoring was performed before the start of the treatment period (baseline) and from day 21 to 29, inclusive. The primary endpoint was change from baseline in the standard deviation (SD) of 24-h blood glucose values, measured daily for 7 days (day 22-28) of the treatment period. Secondary and additional efficacy endpoints included changes in glycemic parameters and the rate of DPP4 inhibition, respectively. Adverse events (AEs) were monitored to assess safety. RESULTS: Mean change from baseline in the SD of 24-h blood glucose (95% confidence interval) at day 28 was - 7.35 (- 15.13, 0.44) for trelagliptin and - 11.63 (- 18.67, - 4.59) for alogliptin. In both treatment groups, glycemic parameters improved and the rate of DPP4 inhibition was maintained. Three patients reported AEs; no severe treatment-emergent AEs were reported in either group. CONCLUSION: Once-weekly trelagliptin and once-daily alogliptin improved glycemic control and reduced GV without inducing hypoglycemia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02771093) and JAPIC (JapicCTI-163250). FUNDING: Takeda Pharmaceutical Company, Ltd.

Multifocal hyperfunctioning thyroid carcinoma without metastases.

Hyperthyroidism due to thyroid carcinoma is rare, and most cases are caused by hyperfunctioning metastatic thyroid carcinoma rather than primary carcinoma. Among primary hyperfunctioning thyroid carcinoma, multifocal thyroid carcinoma is exceedingly rare, with the only one case being reported in the literature. Here, we describe the case of a 62-year-old woman with multifocal functioning thyroid carcinoma. Technetium-99m (99m Tc) scintigraphic imaging showed four hot areas in the thyroid gland. Histopathological examination of all four nodules revealed papillary carcinoma, corresponding to hot areas in the 99m Tc scintigram. DNA sequencing of the thyrotropin receptor (TSH-R) gene from all nodules revealed no mutation, indicating that activation of TSH-R was unlikely in the pathophysiogenesis of hyperfunctioning thyroid carcinoma in the present case.