repaglinide / Generic mfg. - LARVOL DELTA

Potential protective associations of antidiabetic and lipid-lowering therapies with retinal vein occlusion risk: a systematic review and meta-analysis. (PubMed, Eye (Lond)) - "Studies suggest metformin monotherapy halved risk [hazard ratio (HR) = 0.46, 0.30-0.73], and glucagon-like peptide-1(GLP-1) receptor agonists were associated with reduced risk compared to dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR = 0.73, 0.54-0.98)...Other conventional agents (repaglinide, thiazolidinediones, sulfonylureas, α-glucosidase inhibitors, insulin) yielded imprecise or null estimates...Additionally, the role of SGLT-2 inhibitors remains uncertain. These indicators warrant confirmation in prospective studies and may inform tailored retinal vascular risk reduction strategies in patients with diabetes and dyslipidaemia."

Journal • Retrospective data • Review • Diabetes • Dyslipidemia • Metabolic Disorders • Retinal Vein Occlusion • Thrombosis

An elderly patient with type 2 diabetes who developed a hyperglycemic emergency and showed a marked decline in insulin secretion, but she was able to be weaned off insulin by alleviating glucose toxicity and adjusting her medication: A case report (PubMed, Nihon Ronen Igakkai Zasshi) - "After initiating dulaglutide and repaglinide treatment, insulin therapy, which peaked at 23 units/day, was discontinued. Although insulin withdrawal was predicted to be challenging based on previous reports, it was successfully performed in the present case. This case represents a suggestive example that highlights the relevant considerations for evaluating the residual insulin secretory function."

Journal • CNS Disorders • Dermatology • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Using physiologically based pharmacokinetic modelling to optimize repaglinide and irbesartan dosing in Chinese population with SLCO1B1 polymorphism. (PubMed, Br J Clin Pharmacol) - "A PBPK model was built for REP and IRB and used to predict DDI for the population with SLCO1B1 c.521 T > C gene polymorphism. Moreover, the model was applied to provide individualized drug recommendations for the SLCO1B1 c.521TT genotype population."

Journal • PK/PD data

Pharmacokinetic Drug-Drug Interactions of Imlunestrant in Healthy Female Participants of Nonchildbearing Potential. (PubMed, Clin Transl Sci) - "Participants tolerated imlunestrant at 200-800-mg doses, alone or with a CYP3A inhibitor (itraconazole), CYP3A inducer (carbamazepine), P-glycoprotein (P-gp) inhibitor (quinidine), and substrates of CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), CYP3A (midazolam), P-gp (digoxin), and BCRP (rosuvastatin). Imlunestrant had no DDIs with CYP2C8 (repaglinide), CYP2C19 (omeprazole), and CYP3A4 (midazolam) substrates, or a P-gp inhibitor (quinidine), but weakly inhibited dextromethorphan (CYP2D6 substrate), digoxin (P-gp substrate), and rosuvastatin (BCRP substrate) clearance. Thus, considerations should be taken when imlunestrant is coadministered with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP2D6 and P-gp substrates where small changes in exposure may lead to toxicities."

Journal • PK/PD data • Breast Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Pain • Solid Tumor • CYP2C19 • ER • HER-2

Green Sensitive Derivative Emission Spectrofluorimetry for the Estimation of Repaglinide and Febuxostat Simultaneously in Dosage Forms and Spiked Human Plasma. (PubMed, Luminescence) - "The validation was performed in accordance with ICH guidelines and the amplitude first derivative (1D) versus concentrations curves covered concentration ranges of 0.01-0.18 μg/mL for REP and 0.03-0.2 μg/mL for FEB. The suggested approach was effectively used to determine the two drugs in spiked human plasma samples in ranges 0.01-0.2 μg/mL for REP and 0.05-0.2 μg/mL for FEB. The proposed technique was effectively used to identify the (REP) and (FEB) in multiple pharmaceutical products."

Journal

Drug-Drug Interaction Between Eugenol and Repaglinide in Type 2 Diabetes Mellitus and Its Potential Mechanism. (PubMed, J Vis Exp) - "EUG also inhibited the activity of CYP3A with an IC50 of 7.90 ± 1.79 µM. Co-administration of EUG promoted the hypoglycemic effect of RPG through enhancing RPG systemic exposure in T2DM rats, potentially by improving RPG metabolic stability and inhibiting CYP3A activity."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Investigation of Thymoquinone as an Inhibitor of CYP2C8/EET Axis. (PubMed, Chembiochem) - "The current results reveal the followings: (a) thymoquinone could markedly inhibit CYP2C8 based on study using amodiaquine N-deethylation in human liver microsomes (HLM); (b) thymoquinone could strongly interact with the active site of the human CYP2C8 as demonstrated by molecular docking analysis; (c) thymoquinone could restrict the metabolic depletion of repaglinide (a CYP2C8 substrate) in rat liver microsomes; (d) thymoquinone altered the pharmacokinetic profile of repaglinide (a CYP2C8 substrate) in rats, resulting in repaglinide's increased systemic exposure and reduced clearance; (e) thymoquinone could retard EET's formation in HLM. Further studies are warranted to evaluate the biological significance of thymoquinone-mediated modulation of the CYP2C8/EET axis in relevant cancer models."

Journal • Oncology • CYP2C8

Predicting pH-Dependent Solubility Enhancement and Precipitation Suppression in Drug-Cyclodextrin-Arginine Formulations. (PubMed, Pharmaceutics) - "The approach was applied to representative ternary systems containing repaglinide, sulfadiazine, cefixime, and meloxicam. These observations support the importance of pH and multicomponent interactions in controlling formulation performance in cyclodextrin-containing systems. The obtained profiles may support preliminary optimization of formulation pH and excipient composition before experimental screening."

Journal

Ultrafast affinity extraction with non-covalent entrapment for biointeraction analysis: development and applications to single- and multi-site drug-protein binding. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "This combined approach is evaluated using racemic warfarin and repaglinide as model drugs with known single-site or multi-site binding to this protein. The binding and rate constants determined by this method are also compared to reference values, including results obtained by UAE using a covalently immobilized capture agent. The results are then used to identify the potential strengths or limitations of this approach and to provide guidelines on how this method can be applied in the future to examine other types of biointeractions."

Journal

Identification of a Functional CYP2C8 Variant Allele that Alters Splicing, Reduces Protein Expression, and Increases Drug Exposure. (PubMed, Clin Pharmacol Ther) - "Sequencing data from a study with montelukast revealed a novel functional CYP2C8 allele (rs2071426, CYP2C8*19), predicted to create an intronic splice donor site. Participants with the poor function SLCO1B1 genotype showed a 32% smaller fold increase in repaglinide AUC0-∞ following gemfibrozil than participants with the normal function SLCO1B1 genotype (P = 0.0045). This study characterizes CYP2C8*19 as a novel decreased function allele and shows that CYP2C8 and SLCO1B1 genotypes affect the gemfibrozil-repaglinide interaction."

Journal • CYP2C8 • SLCO1A2 • SLCO1C1

A Drug-drug Interaction Study to Evaluate the Effects of Pelabresib on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Oral Contraceptive in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology

The Impact of Polymers in Amorphous Solid Dispersion on the Bioavailability of Sulfonylureas and Meglitinides. (PubMed, Drug Des Devel Ther) - "Studies consistently show that ASD formulations of antidiabetic drugs such as glimepiride, repaglinide, gliclazide, gliquidone, and glyburide enhance insulin secretion and contribute to more effective glycemic control, showing the potential of ASD in improving the therapeutic performance of poorly soluble antidiabetic agents. By enhancing solubility, stability, and bioavailability, ASD technology holds significant promise for developing more potent and effective antidiabetic therapies, ultimately supporting better patient care and addressing the global burden of diabetes mellitus."

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

Effect of ripretinib on the pharmacokinetics (PK) of repaglinide, a sensitive CYP2C8 probe substrate, in adult patients (pts) with advanced gastrointestinal stromal tumor (GIST). (ASCO 2026) - P1 | "Funded by Deciphera Pharmaceuticals, LLC, a member of ONO Pharma Clinical Trial Registration Number: NCT04530981 Background: Ripretinib is a switch-control tyrosine kinase inhibitor (TKI) indicated for the treatment of adult pts with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib is a weak inhibitor of CYP2C8, with no impact on absorption and a small, clinically insignificant increase in total repaglinide exposure. The safety profile of ripretinib was consistent with its established use in advanced GIST. This study provides the basis for approved concomitant use of ripretinib with CYP2C8 substrates."

Clinical • Metastases • PK/PD data • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Assessment of gedatolisib (geda) pharmacokinetics (PK), drug-drug interactions (DDI), and exposure-safety and exposure-efficacy relationships. (ASCO 2026) - P1, P1b, P3 | " With concomitant geda + repaglinide, Cmax and AUCinf were 43.7% and 4.7% lower, respectively); geda + rosuvastatin, Cmax and AUCinf were 36.4% and 44.4% higher; geda + metformin, Cmax and AUCinf were 45.5% and 67.7% higher. With concomitant geda + itraconazole, Cmax and AUCinf were 17.3% and 1.4% lower... Dose modification of CYP2C8, BCRP and MATE1/2-K substrates is not required when co-administered with geda, and geda dose modification is not required with P-gp inhibitors. Exposure-efficacy and exposure-safety assessments support the currently recommended geda dose of 180 mg administered in a 3w on / 1w off regimen."

Clinical • PK/PD data • Breast Cancer • Dental Disorders • Diabetes • HER2 Breast Cancer • HER2 Positive Breast Cancer • Mucositis • Oncology • Solid Tumor • Stomatitis • HER-2

Collecting Metabolite Pharmacokinetics in Drug-Drug Interaction Studies: A Review of Industry Practices and Data Utilization. (PubMed, Clin Pharmacokinet) - "Based on these findings, we formulated criteria for deciding on the relevance of metabolite endpoints in clinical DDI studies."

Journal • PK/PD data • Review • CYP2C19 • CYP2C9 • CYP3A4

Repaglinide Provokes Dose-Dependent Myocardial Toxicity via Disrupting HIF-1α, TLR4/MyD88, and NF-κB Pathway: A Biochemical, Radiological, and Histological Approach. (PubMed, J Appl Toxicol) - "Collectively, these results show that RPG causes profound cardiotoxicity in a dose-dependent manner, mediated by oxidative stress, inflammatory activation, hypoxia-angiogenic imbalance, apoptotic signaling, and structural remodeling. This study demonstrates the importance of thorough cardiovascular safety evaluation of antidiabetic therapies and calls for further translational evaluation to evaluate potential clinical implications."

IO biomarker • Journal • Cardiovascular • Diabetes • Fibrosis • Inflammation • ANGPT1 • BCL2 • CASP3 • CASP9 • HIF1A • IL1B • IL6 • KDR • MYD88 • TLR4 • TNFA

To Determine the Effect of CYP Induction Following Administration of Nirogacestat in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany | Active, not recruiting ➔ Completed

Trial completion

A Drug-drug Interaction Study to Evaluate the Effects of Pelabresib on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Oral Contraceptive in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

Trial initiation date • Oncology

Safety, tolerability, pharmacokinetics, and pharmacodynamics of zapnometinib: results from a phase I clinical study. (PubMed, Front Pharmacol) - "The DDI phase assessed the effect of zapnometinib on CYP2C8 and CYP2C9 activity using repaglinide and celecoxib as probe substrates. This phase 1 study demonstrates that zapnometinib has a favorable safety and tolerability profile, predictable pharmacokinetics, and potent pharmacodynamic activity. The results support further clinical development of zapnometinib for therapeutic indications involving dysregulated MAPK/ERK signaling."

Clinical • Journal • P1 data • PK/PD data • Infectious Disease • Inflammation • Pain • CYP2C9

CDAK539A12102: A clinical trial to learn about the effects of DAK539 on the blood levels of repaglinide, midazolam, drospirenone, and ethinyl estradiol in people with advanced cancer (clinicaltrialsregister.eu) - P1 | N=9 | Not yet recruiting | Sponsor: Novartis Pharma AG

New P1 trial • Oncology

Actions of Midostaurin as Cation Channel and Tyrosine Kinase Inhibitor in Diffuse Intrinsic Pontine Glioma Cell Lines. (PubMed, Cancers (Basel)) - "TKIs targeting different kinases such as everolimus, crizotinib, dasatinib, erlotinib, lapatinib, perifosine and midostaurin (0.001-100 μM) were investigated on cell proliferation and ion channel currents...These currents were sensitive to the KATP channel inhibitors glibenclamide and repaglinide and were fully reduced by the unselective blocker TEA-BaCl2...In SU-DIPG-36 cells midostaurin causes a concentration-dependent upregulation of autophagy markers. The inhibition of cation channel currents by midostaurin in SU-DIPG-36 and SU-DIPG-50 cells and the autophagy potentiation in SU-DIPG-36 cells can be novel mechanisms in DIPG."

Journal • Preclinical • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Oncology • Solid Tumor

Biodistribution of Cerivastatin, Repaglinide, Glyburide, Rosuvastatin, and Valsartan in Cynomolgus Monkeys and PBPK Analysis. (PubMed, AAPS J) - "To understand VSS and tissue biodistribution of substrate drugs in monkeys, we have performed a series of monkey PK and tissue distribution studies, as well as data analysis with physiologically based pharmacokinetic (PBPK) modeling for several OATP1B substrates (i.e., cerivastatin, repaglinide, glyburide, rosuvastatin, and valsartan). We find that there are unexpectedly high accumulations of these compounds in monkey intestines potentially involving transporter mediated active uptake, which contributed to the higher-than-expected VSS values."

Journal

A Drug-drug Interaction Study to Evaluate the Effects of Pelabresib on the Pharmacokinetics of Repaglinide, Midazolam, and Combined Oral Contraceptive in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Dec 2029 ➔ Apr 2028 | Trial primary completion date: Nov 2029 ➔ Mar 2028

Trial completion date • Trial primary completion date • Oncology

To Determine the Effect of CYP Induction Following Administration of Nirogacestat in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: SpringWorks Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2026 ➔ Mar 2026

Enrollment closed • Trial completion date • Trial initiation date

A Drug Drug Interaction Study to Evaluate the Effect of VCT220 on the Pharmacokinetics of Repaglinide, Rosuvastatin, and Digoxin in Healthy, Overweight, and Obese Subjects (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Vincentage Pharma Co., Ltd | Active, not recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Aug 2025 | Trial primary completion date: Oct 2025 ➔ Jul 2025

Trial completion • Trial completion date • Trial primary completion date • Genetic Disorders • Obesity