Sulfonylurea prescription patterns in elderly patients with type 2 diabetes mellitus: A comprehensive analysis of real-world data from pharmacies in Japan.

AIMS/INTRODUCTION: The study aim was to investigate sulfonylurea prescription patterns in elderly patients (age ≥65 years) with type 2 diabetes mellitus in Japan. Sulfonylurea use among older adults has been insufficiently examined, despite the associated risks of hypoglycemia. MATERIALS AND METHODS: This retrospective cross-sectional survey entailed analysis of Japanese pharmacy data, extracted from the Musubi database, for patients (age 20-100 years) prescribed sulfonylureas between November 2022 and October 2023. Dose distribution, adherence to the Diabetes Treatment Guidelines for the Elderly 2023 and coprescription of other diabetes medications were investigated. RESULTS: Of the total 91,229 patients, 80.1% were prescribed glimepiride, 16.3% gliclazide and 3.6% glibenclamide. In patients aged ≥65 years, exceeding the recommended dose (>1 mg/day for glimepiride, >40 mg/day for gliclazide) was numerically higher for glimepiride (25.0%) than for gliclazide (7.8%). The most common prescribing patterns were quadruple therapy with a sulfonylurea, a dipeptidyl peptidase-4 inhibitor, an sodium-glucose transporter 2 inhibitor and a biguanide in patients aged 65 to <75 years, and dual therapy with a sulfonylurea and a dipeptidyl peptidase-4 inhibitor in patients aged ≥75 years. Unfortunately, glinide was coprescribed for 338 (0.5%) of elderly patients. Insulin was coprescribed for 3,682 (5.6%) of elderly patients. CONCLUSIONS: Analysis of real-world sulfonylurea prescription data found guideline non-adherence, namely, excessive prescription of glimepiride, use of glibenclamide in elderly patients, and common coprescription with dipeptidyl peptidase-4 inhibitors. These findings might provide an opportunity to reconsider the treatment of patients with type 2 diabetes mellitus who are over-prescribed sulfonylureas to reduce residual risks, such as hypoglycemia.

Discovery of Novel 2-Carbamoyl Morpholine Derivatives as Highly Potent and Orally Active Direct Renin Inhibitors.

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin, the first and rate-limiting enzyme of the RAAS, is an attractive target for the treatment of hypertension and cardiovascular/renal diseases. Therefore, various direct renin inhibitors (DRIs) have been researched over recent decades; however, most exhibited poor pharmacokinetics and oral bioavailability due to the peptidomimetic or nonpeptidomimetic structures with a molecular weight (MW) of >600, and only aliskiren is approved. This study introduces a novel class of DRIs comprised of a 2-carbamoyl morpholine scaffold. These compounds have a nonpeptidomimetic structure and a MW of <500. The representative compound 26 was highly potent despite not occupying S1'-S2' sites or the opened flap region used by other DRIs and exerted a significant antihypertensive efficacy via oral administration on double transgenic mice carrying both the human angiotensinogen and the human renin genes.

The Current Status of Drug Discovery and Development as Originated in United States Academia: The Influence of Industrial and Academic Collaboration on Drug Discovery and Development.

Academic drug discovery is a vital component to current drug discovery and development environments. In this study, we investigated 798 drug discovery projects that took place between 1991 and 2015 at 36 academic institutions in the United States. The observed success rates of academic drug discovery and development were 75% at phase I, 50% at phase II, 59% at phase III, and 88% at the new drug application/biologics license application (NDA/BLA) phase. These results were similar to the corresponding success rates of the pharmaceutical industry. Collaboration between academic institutions and the pharmaceutical industry seemed more important at later stages than earlier ones; all projects that succeeded at phase III or the NDA/BLA stage involved academic-industrial collaboration. Many academic research projects involved neoplasms and infectious diseases, and were focused on small molecules and biologics. The success rates and possible effects of academic-industrial collaboration seemed to vary depending on disease domains and drug modalities.

(1-nosyl-5-nitroindol-3-yl)methyl ester: a novel protective group for carboxylic acids.

The usefulness of (1-nosyl-5-nitroindol-3-yl)methyl esters as a novel protective group for carboxylic acid is fully demonstrated. The novel protective group is stable under a broad range of conditions and can easily be deprotected under the mild conditions used for removal of the nosyl (Ns) group. It is orthogonal to the existing protective groups for carboxylic acids such as t-butyl and allyl esters.

Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates.

Screening of our in-house compound library comprised of intermediates of natural product synthesis projects resulted in discovering two novel gamma-secretase inhibitors, which coincidently had similar moieties, that is, cyclohexenone and two aryl groups arranged on the core six-membered ring. Structure-activity relationship studies of these compounds were also developed.