Zafatek (trelagliptin) / Takeda - LARVOL DELTA

Pharmacokinetics of Trelagliptin in Rats after Exposure to Acute and Chronic High Altitude Hypoxia. (PubMed, Curr Drug Metab) - " The study demonstrated that high-altitude hypoxia significantly altered trelagliptin's phar-macokinetics, slowing clearance, prolonging elimination half-life and residence time, and increasing bio-availability. These changes suggested that the optimal therapeutic dosage of trelagliptin should be reas-sessed under hypoxic exposure."

Journal • PK/PD data • Preclinical • SLC22A2

Introducing a Novel Once-weekly Dipeptidyl Peptidase 4 Inhibitor: Trelagliptin in India. (PubMed, J Assoc Physicians India) - "In a randomized phase 3 clinical trial involving patients with glycated hemoglobin (HbA1c) ≥8%, trelagliptin showed greater HbA1c reduction (-1.25%) as compared to vildagliptin (-1.15%) and a similar safety profile. This article outlines the development and regulatory journey leading to trelagliptin's first approval in India by the Central Drugs Standard Control Organization (CDSCO) in December 2024. Phase 4 real-world evidence studies are currently ongoing in India to assess long-term safety and efficacy."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison Between Efficacy of Trelagliptin and Sitagliptin in Type II Diabetic Patients (clinicaltrials.gov) - P3 | N=126 | Enrolling by invitation | Sponsor: Khyber Medical College, Peshawar

New P3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Once-Weekly Trelagliptin As Compared to Twice-Daily Vildagliptin in Indian Patients With Type 2 Diabetes Mellitus: A Randomized, Phase 3, Non-inferiority Clinical Trial. (PubMed, Cureus) - "The study drug exhibited a favorable safety profile, with no major adverse events reported. Overall, trelagliptin proved to be both efficacious and well-tolerated, demonstrating non-inferiority to vildagliptin."

Head-to-Head • Journal • P3 data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Trelagliptin Ameliorates Memory Decline in Diabetic Rats through the AMPK/AKT/GSK-3β Pathway in the Cerebral Cortex. (PubMed, ACS Omega) - "Notably, trelagliptin upregulated the expression of postsynaptic density protein 95 (PSD95) and synaptotagmin 1 (SYT1) while downregulating amyloid precursor protein (APP) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). These findings suggest that trelagliptin alleviates cognitive impairment in diabetic rats, likely through AMPK-AKT-GSK-3β-mediated mitigation of oxidative stress, enhancement of synaptic plasticity, and reduction of Aβ accumulation."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • DLG4 • GPX4 • SOD2

Comparison of Once-Weekly Trelagliptin vs. Once-Daily Vildagliptin for HbA1c Reduction in Type 2 Diabetes (clinicaltrials.gov) - P=N/A | N=102 | Active, not recruiting | Sponsor: PNS Hafeez - Naval Hospital

New trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Comparison of Once-Weekly Trelagliptin Vs. Once-Daily Vildagliptin for HbA1c Reduction in Type 2 Diabetes (clinicaltrials.gov) - P=N/A | N=102 | Active, not recruiting | Sponsor: Lahore General Hospital

New trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Effects of dulaglutide and trelagliptin on beta-cell function in patients with type 2 diabetes: a randomized controlled study: DUET-beta study. (PubMed, Diabetol Int) - "Fifty patients with type 2 diabetes who received metformin with or without basal insulin were randomized to receive dulaglutide or trelagliptin. However, dulaglutide promoted improved HOMA2-%β levels compared to trelagliptin and body fat mass was reduced without loss of skeletal muscle mass (UMIN-CTR 000024164). The online version contains supplementary material available at 10.1007/s13340-024-00717-6."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Trelagliptin relieved cognitive impairment of diabetes mellitus rats: Involvement of PI3K/Akt/GSK-3β and inflammation pathway. (PubMed, Exp Gerontol) - "Furthermore, PI3K/Akt/GSK-3β has been activated, and synaptic plasticity has been modified during this process. In conclusion, trelagliptin improved the cognitive lesion in DM rats by suppressing the activation of the inflammatory route and by activating the PI3K/Akt/GSK-3β pathway at the same time, as well as interacting with the pathways that protect neurons, which still need further research."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Diabetes • Inflammation • Metabolic Disorders • IL1B • IL6 • TNFA

Impacts of trelagliptin and remogliflozin alone and in combination with Alpha Lipoic Acid on cardiac function in streptozotocin-induced diabetes mellitus in rats. (PubMed, Cell Mol Biol (Noisy-le-grand)) - "The combination of trelagliptin, remogliflozin, and ALA may have additional clinical value in managing DCM by targeting oxidative stress, inflammation, and glucotoxicity. However, further research is needed to validate these findings and explore their potential clinical applications."

Biomarker • Combination therapy • Journal • Preclinical • Cardiomyopathy • Cardiovascular • Diabetes • Inflammation • Metabolic Disorders • Myositis • CTSB • NFKB1 • TXNIP

Computational tools for exploring peptide-membrane interactions in gram-positive bacteria. (PubMed, Comput Struct Biotechnol J) - "Herein, we present a comprehensive survey of diverse computational approaches that are suitable for detecting QSPs and QS interference molecules. This review highlights the utility of these methods for developing potential biomarkers against infectious Gram-positive pathogens."

Gram positive • Journal • Review • Infectious Disease

Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Type 2 Diabetes Mellitus Patients With Severe Renal Impairment or End-stage Renal Disease" (clinicaltrials.gov) - P=N/A | N=87 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Comparison of Adverse Events Occurred During Administration of Dipeptidyl Peptidase-4 Inhibitor in Patients with Diabetes Using FDA Adverse Event Reporting System. (PubMed, Clin Drug Investig) - "Although it is impossible to select a DPP-4 inhibitor with aROR of < 1.000 of all occurrences of adverse events, these results may be used for drug selection when the patient has adverse events that need to be avoided. We provided the sample code of software R that can reproduce the results."

Adverse events • Journal • Acute Kidney Injury • Diabetes • Immunology • Metabolic Disorders • Nephrology • Renal Disease

Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Type 2 Diabetes Mellitus Patients With Severe Renal Impairment or End-stage Renal Disease" (clinicaltrials.gov) - P=N/A | N=87 | Active, not recruiting | Sponsor: Takeda | Trial completion date: Oct 2022 ➔ Jan 2023 | Trial primary completion date: Oct 2022 ➔ Jan 2023

Trial completion date • Trial primary completion date • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Prediction of pharmacokinetics and pharmacodynamics of trelagliptin and omarigliptin in healthy humans and in patients with renal impairment using physiologically based pharmacokinetic combined DPP-4 occupancy modeling. (PubMed, Biomed Pharmacother) - "The present PBPK-DO model can simultaneously predict PK and PD of TRE and OMA in humans and also provide valuable recommendations for dosing adjustment in renal impairment patients, which cannot be achieved by alone depending on PK change."

Journal • PK/PD data • Renal Disease

ABCC8-Related Maturity-Onset Diabetes of the Young: Clinical Features and Genetic Analysis of One Case. (PubMed, Pediatr Diabetes) - "The diagnosis of maturity-onset diabetes of the young (MODY)12 was confirmed in our patient. The ABCC8 variant inhibited both ubiquitination and autophagy lysosome degradation pathways, especially the ubiquitination degradation pathway."

Journal • Diabetes • Metabolic Disorders • Targeted Protein Degradation • Type 2 Diabetes Mellitus

Safety and efficacy of once weekly dipeptidyl-peptidase-4 inhibitor trelagliptin in type-2 diabetes: A meta-analysis. (PubMed, Diabetes Metab Syndr) - "Once weekly trelagliptin has good glycaemic efficacy and well tolerated in people with T2DM."

Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Investigation of Pharmacokinetic Parameters of Trelagliptin in Egyptian Volunteers Using Sensitive LC-MS/MS: A Comparative Study with a Japanese Population. (PubMed, J Anal Methods Chem) - "Alogliptin was used as internal standard (IS) because of its structure similarity to TLN. The proposed method was successfully applied to a pharmacokinetic study conducted on Egyptian volunteers. No dose modification is required upon comparing the pharmacokinetic parameters of the current study and previous studies on non-Egyptian volunteers."

Clinical • Journal • PK/PD data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Patients With Type 2 Diabetes Mellitus" (clinicaltrials.gov) - P=N/A; N=3198; Completed; Sponsor: Takeda; Active, not recruiting ➔ Completed

Clinical • Trial completion • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Trelagliptin ameliorates IL-1β-impaired chondrocyte function via the AMPK/SOX-9 pathway. (PubMed, Mol Immunol) - "Collectively, our study demonstrates that the DPP-4 inhibitor Trelagliptin has a protective effect on chondrocyte function. Trelagliptin may have the potential role to antagonize chondrocyte-derived inflammation in OA."

Journal • Diabetes • Immunology • Inflammation • Metabolic Disorders • Oncology • Osteoarthritis • Pain • Rheumatology • Type 2 Diabetes Mellitus • AMPK • CXCL8 • IL1B • IL6 • TNFA

Specified Drug-Use Survey of Trelagliptin Tablets "Survey on Long-term Use in Type 2 Diabetes Mellitus Patients With Severe Renal Impairment or End-stage Renal Disease" (clinicaltrials.gov) - P=N/A; N=87; Active, not recruiting; Sponsor: Takeda; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Chronic Kidney Disease • Diabetes • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Trelagliptin ameliorates oxygen-glucose deprivation/reperfusion (OGD/R)-induced mitochondrial dysfunction and metabolic disturbance of endothelial cells. (PubMed, Hum Cell) - "After co-administration of the inhibitor of the AMPK pathway, the effects of Trelagliptin on mitochondrial function and metabolic alterations were significantly abolished. Taken together, our data indicate that Trelagliptin ameliorated OGD/R-induced mitochondrial disturbance and metabolic changes by activating the AMPK pathway."

Journal • Cardiovascular • Diabetes • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus

Cardiovascular events and all-cause mortality in patients with type 2 diabetes treated with dipeptidyl peptidase-4 inhibitors: An extensive meta-analysis of randomized controlled trials. (PubMed, Nutr Metab Cardiovasc Dis) - "As a class, DPP4i are not associated with any increase or reduction of MACE, all-cause mortality, and heart failure. Saxagliptin seems to be associated with an increased risk of hospitalization for heart failure."

Journal • Retrospective data • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus

The anti-diabetic drug trelagliptin induces vasodilation via activation of Kv channels and SERCA pumps. (PubMed, Life Sci) - "From these results, we concluded that the vasodilatory effect of trelagliptin was associated with the activation of Kv channels (primary the Kv7.X subtype) and SERCA pump regardless of other K channels, Ca channels, cAMP/PKA-related or cGMP/PKG-related signaling pathways, and the endothelium. Therefore, caution is required when prescribing trelagliptin to the patients with hypotension and diabetes."

Journal • Diabetes • Hypotension • Metabolic Disorders • PXN

Preparation of (R)-3-aminopiperidine by resolution with optically active cyclic phosphoric acids. (PubMed, Chirality) - "(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e."

Journal