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Elucidation of DPP-4 involvement in systemic distribution and renal reabsorption of linagliptin by PBPK modeling with a cluster Gauss-Newton method.
Clin Transl Sci
October 2024
Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Yokohama-shi, Kanagawa, Japan.
The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (LNG) exhibits target-mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP-4 (sDPP-4) and tissue transmembrane DPP-4 (tDPP-4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild-type mice, but not in Dpp-4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP-4-related renal reabsorption of LNG, we employed physiologically-based pharmacokinetic (PBPK) modeling combined with a cluster Gauss-Newton method (CGNM).
View Article and Find Full Text PDFIntense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial.
BMJ
October 2024
The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
Objective: To evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia.
Design: Multicentre, open label, randomised trial.
Setting: 15 hospitals in China between December 2017 and December 2020.
Sustained linagliptin administration: superior glycemic control and less pancreatic injury in diabetic rats.
Pharm Dev Technol
October 2024
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
While linagliptin is the most potent dipeptidyl peptidase 4 inhibitor, its use is limited due to poor bioavailability and the potential risk of pancreatic injury. Here, we investigated whether the sustained weekly administration of linagliptin could provide better effect compared to frequent daily oral administration. Type 2 diabetes was induced by feeding rats a high fructose/fat/salt diet followed by STZ injection.
View Article and Find Full Text PDFConcomitant Use of Oral Anticoagulants with Oral Dipeptidyl Peptidase-4 Inhibitors and Serious Bleeding Events.
Clin Pharmacol Ther
September 2024
Center for Real-World Effectiveness and Safety of Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
In a prior screening study, saxagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i), was found to have an increased rate of serious bleeding when used concomitantly with several oral anticoagulants (OACs). We aimed to confirm or refute the associations between concomitant use of individual OACs and DPP-4is and serious bleeding in a large US database, using self-controlled case series (SCCS) and case-crossover (CCO) designs. The study population was eligible Medicare beneficiaries co-exposed to a DPP-4i (precipitant) and either an OAC (object drug) or lisinopril (negative control object drug) in 2016-2020.
View Article and Find Full Text PDFTreating hyperglycaemia in a patient with maternally inherited diabetes and deafness with an inhibitor of dipeptidyl peptidase-4: a case report and two-year follow-up.
Acta Diabetol
December 2024
Department of Endocrinology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanpu Road 298, Nanjing, China.
Maternally inherited diabetes and deafness (MIDD) is a mitochondrial disorder with diverse characteristics, which make early diagnosis difficult. We report a case of 32-year-old woman with diabetes who was admitted due to weight loss and poor glycemic control. She had a history of gestational diabetes at age 26.
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