Marizev (omarigliptin) / Merck (MSD) - LARVOL DELTA

Dipeptidyl peptidase-4 inhibitors and diabetic retinopathy in type 2 diabetes: A network meta-analysis of randomized clinical trials. (PubMed, J Diabetes Complications) - "Current randomized evidence indicates class-level neutrality of DPP-4 inhibitors on DR incidence, with no dose-response signal. Choice among gliptins may therefore be guided primarily by glycemic efficacy, safety, and participant characteristics rather than retinal risk."

Clinical • Journal • Retrospective data • Review • Diabetes • Diabetic Retinopathy • Metabolic Disorders • Retinal Disorders • Type 2 Diabetes Mellitus

Omarigliptin/shikonin combination alleviates cyclosporine-induced nephrotoxicity: The role of sirtuin 1, glucagon-like peptide-1, HMGB1/RAGE/TLR4 signaling, and p38/ERK/JNK MAPKs. (PubMed, Hum Exp Toxicol) - "Additionally, omarigliptin and/or shikonin elicited a significant amelioration of the inflammatory response and cellular differentiation and a significant improvement of the renal tissue disruptive changes elicited by cyclosporine. These effects were evident with omarigliptin/shikonin combination when compared to the groups treated with each agent alone.ConclusionOmarigliptin/shikonin combination suggests potential therapeutic benefit for the mitigation of cyclosporine nephrotoxicity, possibly via their effects on dipeptidyl peptidase 4 activity and GLP-1 levels with subsequent modulation of the redox status, cellular proliferation, and the inflammatory pathways."

Journal • Immunology • Inflammation • Transplant Rejection • Transplantation • HMGB1 • SIRT1

A Six-Gene Mitochondrial Signature Predicts Prognosis in Dedifferentiated Thyroid Cancer. (PubMed, Int J Gen Med) - "A total of 41 drugs were predicted to have potential therapeutic effects, including omarigliptin, bepridil and bortezomib. Finally, qRT-PCR validation demonstrated that SLC26A4, KCNQ1, PMAIP1, DPP4, and NOX4 had expression trends consistent with public database results. This study identified 6 MDRGs (SLC26A4, SLC25A37, KCNQ1, PMAIP1, DPP4 and NOX4) associated with the prognosis of DDTC, providing valuable scientific insights and references for the targeted therapy and patient stratification of DDTC."

Journal • Metabolic Disorders • Oncology • Solid Tumor • Thyroid Gland Carcinoma • CD4 • DPP4 • KCNQ1OT1 • NOX4 • PMAIP1 • SLC25A3 • SLC25A37 • SLC26A4 • SLC5A7

Evaluation and comparison of efficacy and safety of mitochondrial modulator (Imeglimin) and DPP-4 inhibitors in patients with type 2 diabetes mellitus: A Bayesian network meta-analysis. (PubMed, J Endocrinol Invest) - "Imeg and DPP-4i demonstrated favorable antidiabetic effects and good safety. Imeg exhibited comparable glycemic control to that of DPP-4i. Overall, Alog was the most suitable option among the included DPP-4i for T2DM patients with hyperlipidemia. Tene demonstrated significant efficacy in glycemic control, and can be a first-line choice among the included DPP-4i."

Clinical • Journal • Retrospective data • Review • Diabetes • Dyslipidemia • Infectious Disease • Metabolic Disorders • Type 2 Diabetes Mellitus

Targeting GLP-1 Signaling Ameliorates Cystogenesis in a Zebrafish Model of Nephronophthisis. (PubMed, Int J Mol Sci) - "Our screen revealed that dipeptidyl peptidase-4 (DPP4) inhibitors (Omarigliptin and Linagliptin) and GLP-1 receptor agonists (Semaglutide) significantly reduce cystogenesis in a dose-dependent manner. This compensation was disrupted by the targeted depletion of GLP-1 receptors or the inhibition of adenylate cyclase, resulting in enhanced cyst formation, specifically in the mutant background. Our findings establish a signaling cascade from GLP-1 receptors to adora2ab in terms of regulating ciliary organization and preventing cystogenesis, offering new therapeutic opportunities for NPH through the repurposing of FDA-approved medications with established safety profiles."

Journal • Chronic Kidney Disease • Nephrology • Renal Disease

Omarigliptin ameliorates cisplatin-induced renal damage: Cross-talk between glucagon-like peptide-1, HMGB1/RAGE/TLR4 signaling, and TXNIP/NLRP3 inflammasome/gasdermin D axis. (PubMed, Life Sci) - "Omarigliptin may be introduced, for the first time, as a promising agent to mitigate the nephrotoxic effects of cisplatin."

Journal • Diabetes • Lung Cancer • Metabolic Disorders • Oncology • Ovarian Cancer • Type 2 Diabetes Mellitus • HMGB1 • NLRP3 • TXNIP

Glucagon-like peptide-1 receptor agonists but not dipeptidyl peptidase-4 inhibitors reduce alcohol intake. (PubMed, J Clin Invest) - "Convergent findings across humans, mice, and rats indicate that GLP-1RAs but not DPP-4Is reduce alcohol consumption and may be efficacious in treating AUD."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Endocrine Disorders • Psychiatry

Real-World Evaluation of Omarigliptin for Type 2 Diabetes Meliitus in Bangladesh (clinicaltrials.gov) - P4 | N=938 | Not yet recruiting | Sponsor: Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders | Initiation date: Jun 2024 ➔ Sep 2024

HEOR • Real-world • Real-world evidence • Trial initiation date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Omarigliptin/rosinidin combination ameliorates cyclophosphamide-induced lung toxicity in rats: The interaction between glucagon-like peptide-1, TXNIP/NLRP3 inflammasome signaling, and PI3K/Akt/FoxO1 axis. (PubMed, Biomed Pharmacother) - "Both omarigliptin and rosinidin exhibited a synergistic ability to augment the tissue antioxidant defenses, mitigate the inflammatory pathways, restore glucagon-like peptide-1 levels, modulate high mobility group box 1 (HMGB1)/receptors of advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) axis, downregulate the fibrogenic mediators, and create a balance between the pathways involved in apoptosis and the autophagy signals in the pulmonary tissues. In conclusion, omarigliptin/rosinidin combination may be introduced as a novel therapeutic modality that attenuates the different forms of lung toxicities induced by cyclophosphamide."

Journal • Preclinical • Diabetes • Metabolic Disorders • Oncology • Solid Tumor • HMGB1 • NLRP3 • TXNIP

Real-World Evaluation of Omarigliptin for Type 2 Diabetes Meliitus in Bangladesh (clinicaltrials.gov) - P4 | N=938 | Not yet recruiting | Sponsor: Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders

HEOR • New P4 trial • Real-world • Real-world evidence • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Analysis of omarigliptin forced degradation products by ultra-fast liquid chromatography, mass spectrometry, and in vitro toxicity assay. (PubMed, Biomed Chromatogr) - "Based on the results from forced degradation studies, OMG was found to be labile to hydrolysis, oxidation, photolytic, and thermal stress conditions. The results of this study contribute to the quality control and stability profile of OMG."

Journal • Preclinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. (PubMed, Endocrinol Metab (Seoul)) - "Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM."

Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. (PubMed, Endocrinol Metab (Seoul)) - "Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG). Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM."

Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Omarigliptin inhibits brain cell ferroptosis after intracerebral hemorrhage. (PubMed, Sci Rep) - "In addition, the elevation of iron content, lipid peroxidation and FACL4 after ICH; and reduction of GPX4 and AIFM2; were mitigated by MK3102 in vitro and in vivo. The neuroprotective effect of MK3102 may be related to anti-ferroptosis by regulating GLP-1R after ICH injury."

Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Vascular Neurology • ACSL4 • AIFM2 • GPX4

Insight into Structure Activity Relationship of DPP-4 Inhibitors for Development of Antidiabetic Agents. (PubMed, Molecules) - "Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. Additionally, various synthesis schemes were developed to make several commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and omarigliptin. In conclusion, the use of halogenated scaffolds for the development of DPP-4 inhibitors is likely to be an area of increasing interest in the future."

Journal • Review • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Treatment Burden on Once-Weekly Omarigliptin Versus Daily Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes: Randomized Controlled Trial (ONWARD-DPP4 Study). (PubMed, Diabetes Ther) - "Although this study failed to demonstrate the improvement of DTBQ total score by switching from daily DPP4is to omarigliptin compared with continuing the daily DPP4is, the DTBQ subscale score implementation and flexibility burden score were significantly improved only in the group that switched to omarigliptin, suggesting the possibility of switching from daily DPP4is to omarigliptin to decrease the patients' medication burden."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Omarigliptin Protects the Integrity of the Blood-Brain Barrier After Intracerebral Hemorrhage in Mice. (PubMed, J Inflamm Res) - "Importantly, MK3102 protected the integrity of the BBB after ICH, associated with decreased expression of MMP-9, and preservation of the tight junction proteins ZO-1 and Occludin on endothelial cells through putative degradation of MMP-9, and inhibition of the expression of CX43 on astrocytes. Omarigliptin protects the integrity of the BBB in mice after ICH injury."

Journal • Preclinical • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • DPP4 • MMP9 • OCLN • TJP1

Analytical quality-by-design approach for development and validation of HPLC method for the simultaneous estimation of omarigliptin, metformin, and ezetimibe: application to human plasma and dosage forms. (PubMed, BMC Chem) - "The applicability of the method was extended to the in-vitro assay of the drugs in spiked human plasma samples with high % recoveries (94.3-105.7%). The suggested method was validated in accordance with ICH guidelines."

Journal

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

Cardiovascular Safety of Glimepiride: An Indirect Treatment Comparison of Cardiovascular Safety Outcome Trials of DPP4 Inhibitors (ISPOR-EU 2022) - "Glimepiride has a noninferior risk of 3-Point MACE, all-cause death, and CV death compared to placebo, saxagliptin, sitagliptin, linagliptin, and omarigliptin in T2D patients with increased CV risk. Glimepiride may be used in this population to attain glycemic control, particularly in settings where cost of DPP4Is is a concern."

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

Omarigliptin Mitigates 6-Hydroxydopamine- or Rotenone-Induced Oxidative Toxicity in PC12 Cells by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Actions. (PubMed, Antioxidants (Basel)) - "Collectively, these results demonstrate that OMG alleviates the neurotoxin-induced oxidative toxicity through Nrf2/HO-1-mediated antioxidant, NF-κB-mediated anti-inflammatory, and anti-apoptotic mechanisms in PC12 cells. Our findings elucidating multiple mechanisms of antiparkinsonian activity strongly support the therapeutic potential of OMG in the treatment of PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • BCL2 • CASP3 • HMOX1 • NFKBIA

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

Antidiabetic Omarigliptin Dilates Rabbit Aorta by Activating Kv Channels and the SERCA Pump. (PubMed, Fundam Clin Pharmacol) - "Pretreatment with the voltage-dependent K channel inhibitor 4-aminopyridine significantly attenuated the vasodilatory effect of omarigliptin, whereas pretreatment with the inwardly rectifying K channel inhibitor Ba , ATP-sensitive K channel inhibitor glibenclamide, and large-conductance Ca -activated K channel inhibitor paxilline did not alter its vasodilation. Pretreatment with the sarco/endoplasmic reticulum Ca -ATPase (SERCA) pump inhibitors thapsigargin and cyclopiazonic acid significantly reduced the vasodilatory effect of omarigliptin...Furthermore, pretreatment with the nitric oxide synthase inhibitor L-NAME or small-conductance Ca -activated K channel inhibitor apamin, together with the intermediate-conductance Ca -activated K channel inhibitor TRAM-34, did not influence the vasodilatory effect of omarigliptin. In conclusion, omarigliptin induced vasodilation in rabbit aortic smooth muscle by activating voltage-dependent K channels and the SERCA pump..."

Journal • Preclinical

Anti-Quorum Sensing Activities of Gliptins against Pseudomonas aeruginosa and Staphylococcus aureus. (PubMed, Biomedicines) - "To test the anti-QS activities of gliptins, a detailed molecular docking study was conducted to evaluate the gliptins' binding affinities to P. aeruginosa and S. aureus QS receptors, which helped explain the anti-QS activities of gliptins, particularly sitagliptin and omarigliptin. In conclusion, this study evaluates the possible antivirulence and anti-QS activities of gliptins that could be promising novel candidates for the treatment of aggressive Gram-negative or -positive bacterial infections either alone or as adjuvants to other antibiotics."

Journal • Infectious Disease

Omarigliptin attenuates rotenone-induced Parkinson's disease in rats: Possible role of oxidative stress, endoplasmic reticulum stress and immune modulation. (PubMed, Food Chem Toxicol) - "Moreover, OG ameliorated endoplasmic reticulum (ER) stress in rotenone-administered rats; as evidenced by reduced levels of ER resident proteins such as glucose-regulated protein 78, C/EBP homologous protein and apoptotic caspase-12. In conclusion, this study implies repurposing of OG, as a novel neuroprotective agent due to its antioxidant properties, its effects on ER stress in addition to its anti-inflammatory and anti-apoptotic activities."

Journal • Preclinical • CNS Disorders • Immune Modulation • Immunology • Inflammation • Movement Disorders • Parkinson's Disease • CASP12 • HMOX1