المؤلفون: Arvid Jungnik, Jorge Arrubla Martinez, Leona Plum‐Mörschel, Christoph Kapitza, Daniela Lamers, Claus Thamer, Corinna Schölch, Michael Desch, Anita M. Hennige

المصدر: Diabetes, Obesity and Metabolism. 25:1011-1023

مصطلحات موضوعية: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::9876d7f877a459629520eae3aebc8be6Test
https://doi.org/10.1111/dom.14948Test

المؤلفون: Arvid, Jungnik, Jorge, Arrubla, Leona, Plum-Mörschel, Christoph, Kapitza, Daniela, Lamers, Claus, Thamer, Corinna, Schoelch, Michael, Desch, Anita M, Hennige

المصدر: Diabetes, obesitymetabolism.

الوصف: To report two Phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.A Phase Ia study (NCT03175211) investigated single rising doses (SRDs) of BI 456906 in 24 males with body mass index (BMI) 20-30 kg/mIn the SRD study (N=24), mean bodyweight decreased with increasing BI 456906 dose. In the MRD study, the maximum decreases in placebo-corrected mean bodyweight were at Week 6 (-5.79%, dosage schedule [DS] 1; Part A) and Week 16 (-13.8%, DS7; Part B). BI 456906 reduced plasma amino acids and glucagon, indicating target engagement at GCGRs and GLP-1Rs. Drug-related adverse events (AEs) increased with BI 456906 dose. The most frequent drug-related AE with SRDs was decreased appetite (n=9, 50.0%) and two subjects (8.3%) did not complete the trial due to AEs (nausea and vomiting). During MRD Part A (N=80), 10 subjects (12.5%) discontinued BI 456906, most commonly due to a cardiac or vascular AE (n=6, 7.5%); during Part B (N=45), eight subjects (17.8%) discontinued BI 456906, mainly due to AEs (n=6, 13.3%), most commonly gastrointestinal disorders.BI 456906 produced a placebo-corrected bodyweight loss of 13.8% (Week 16), highlighting potential to promote clinically meaningful bodyweight loss in people with overweight/obesity. This article is protected by copyright. All rights reserved.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::363d0794cb6f4d8649e4db2f3ce3c286Test
https://pubmed.ncbi.nlm.nih.gov/36527386Test

المؤلفون: null Arvid Jungnik, null Jorge Arrubla, null Leona Plum‐Mörschel, null Christoph Kapitza, null Daniela Lamers, null Claus Thamer, null Corinna Schoelch, null Michael Desch, null Anita M. Hennige

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::98723b5cc5f26b186448dcade1dbaad6Test
https://doi.org/10.1111/dom.14948/v2/response1Test

المؤلفون: Juris J. Meier, Daniel R. Quast, Michael A. Nauck, Nina Schenker, Carolyn F. Deacon, Jens J. Holst, Leona Plum‐Mörschel, Christoph Kapitza

المصدر: Meier, J J, Quast, D R, Nauck, M A, Schenker, N, Deacon, C F, Holst, J J, Plum-Mörschel, L & Kapitza, C 2022, ' Acute effects of linagliptin on intact and total glucagon-like peptide-1 and gastric inhibitory polypeptide levels in insulin-dependent type 2 diabetes patients with and without moderate renal impairment ', Diabetes, Obesity and Metabolism, vol. 24, no. 5, pp. 806-815 . https://doi.org/10.1111/dom.14636Test

مصطلحات موضوعية: Blood Glucose, Endocrinology, Diabetes Mellitus, Type 2, Glucagon-Like Peptide 1, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, Insulin, Linagliptin, Gastric Inhibitory Polypeptide

الوصف: AIMS: To investigate the effect of renal impairment on incretin metabolism in patients with type 2 diabetes mellitus (T2DM) before and after treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin.MATERIALS AND METHODS: Long-standing T2DM patients with normal (estimated glomerular filtration rate [eGFR] >90 mL/min/1.73m2 ) and impaired (eGFR RESULTS: Of 115 patients screened, 29 were analysed (15 [51.7%] with and 14 [48.3%] without renal impairment). Renal function differed significantly between the groups (101 ± 11 vs. 47 ± 13 mL/min/1.73m2 ; P CONCLUSIONS: Treatment with linagliptin increases intact incretin levels in patients with T2DM. Impaired renal function does not compromise the effects of linagliptin on active or total incretin levels as well as on glucagon secretion. Thus, treatment with linagliptin is suitable for patients with T2DM, independently of renal function.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ded496cd30437d5814892a737bef3683Test
https://doi.org/10.1111/dom.14636Test

المؤلفون: Christof M. Kazda, Jennifer Leohr, Thomas A. Hardy, Mary Anne Dellva, Christoph Kapitza, Mark Matzopoulos, Mei Teng Loh, Rong Liu, Shobha Reddy, Oliver Klein

المصدر: Diabetes, Obesity and Metabolism. 24:187-195

مصطلحات موضوعية: Blood Glucose, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Pharmacology, Endocrinology, Pharmacokinetics, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Insulin lispro, Dosing, Cross-Over Studies, Insulin Lispro, business.industry, Postprandial Period, Crossover study, Diabetes Mellitus, Type 1, Glucose, Postprandial, Diabetes Mellitus, Type 2, Tolerability, Pharmacodynamics, business, medicine.drug

الوصف: AIMS To compare the pharmacokinetics (PK), glucodynamics (GD) and tolerability following single and multiple daily subcutaneous doses of ultra rapid lispro (URLi) and Humalog® in patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS This was a two-part, randomized, double-blind Phase 1b study. Part A used a six-period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15 minutes before, immediately before, or 15 minutes after the start of the meal. Part B evaluated URLi or Humalog during 2 weeks of multiple daily dosing with a parallel design. The PK and GD were assessed following MMTTs at the beginning and end of the 2 weeks when insulins were administered immediately before the start of the meal. RESULTS URLi increased the insulin exposure within the first 30 minutes postdose by 2.2-fold and reduced the time to the early half-maximal drug concentration by 22.6% compared with Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal. In comparing the same meal-to-dose timing between the insulins, the postprandial glucose excursion over 5 hours was significantly reduced by 29%-105% for all three dose timings (-15, 0 and +15 minutes) with URLi. The PK and GD were sustained after daily subcutaneous dosing for 2 weeks in patients with T2D. URLi had more hypoglycaemic events during the MMTTs; few events occurred for both treatments during the 2 weeks of outpatient dosing. CONCLUSIONS URLi demonstrated accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal-to-dose timings compared with Humalog and was well tolerated in patients with T2D.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bb4eef7c35470da7c8843e3c1b823e41Test
https://doi.org/10.1111/dom.14561Test

المؤلفون: Wolfgang Schmider, Bhaswati Mukherjee, Christoph Kapitza, Lenore Teichert, Irene Nowotny, Leszek Nosek

المصدر: Diabetes, Obesity and Metabolism. 23:674-681

مصطلحات موضوعية: medicine.medical_specialty, Type 1 diabetes, business.industry, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, medicine.disease, Crossover study, Confidence interval, Insulin aspart, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pharmacokinetics, Internal medicine, Pharmacodynamics, Cohort, Internal Medicine, medicine, Dosing, business, medicine.drug

الوصف: AIM To compare the pharmacokinetic exposure of SAR341402 Mix 70/30 (SARAsp -Mix) with US- and European (EU)-approved versions of insulin aspart Mix 70/30 (NovoLog Mix 70/30 [NN-Mix-US]/NovoMix 30 [NN-Mix-EU]) and SAR341402 insulin aspart solution (SAR-Asp) in subjects with type 1 diabetes. MATERIALS AND METHODS This was a randomized, double-blind, crossover trial in two cohorts. Fifty-two subjects received a single subcutaneous 0.3 U/kg dose of each treatment and underwent a euglycaemic clamp procedure lasting for a maximum of 24 hours after dosing. In cohort 1, subjects (N = 36) were exposed once each to SARAsp -Mix, NN-Mix-US and NN-Mix-EU. In cohort 2, subjects (N = 16) were exposed once each to SARAsp -Mix and SAR-Asp. RESULTS Of the 52 subjects randomized, 48 completed all treatment periods. In cohort 1, the extent of exposure (total and maximum concentration) was similar among the three treatments, with the 90% confidence intervals for pairwise treatment ratios meeting the predefined acceptance range (0.80 to 1.25). In cohort 2, statistically significant differences (P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::78bdaafa2c988eb1e480252ceaa93718Test
https://doi.org/10.1111/dom.14260Test

المؤلفون: null Juris J. Meier, null Daniel R. Quast, null Michael A. Nauck, null Nina Schenker, null Carolyn F. Deacon, null Jens J. Holst, null Leona Plum‐Mörschel, null Christoph Kapitza

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d202926564bbd71ab4bc3ef19f7a60b3Test
https://doi.org/10.1111/dom.14636/v3/response1Test

المؤلفون: null Juris J. Meier, null Charlotte Granhall, null Ulrike Hoevelmann, null Andrea Navarria, null Leona Plum‐Moerschel, null Chethana Ramesh, null Andrea Tannapfel, null Christoph Kapitza

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6e7094bb2c3e95b57dba93a1d767520cTest
https://doi.org/10.1111/dom.14632/v2/response1Test

المؤلفون: Eric Zijlstra, Christoph Kapitza, Qianyi Zhang, Helle Linnebjerg, Juliana M. Bue-Valleskey, David E. Coutant, Jennifer Leohr, Tim Heise, Elizabeth Smith Labell, Mary Anne Dellva

المصدر: Diabetes, Obesity & Metabolism

مصطلحات موضوعية: Blood Glucose, medicine.medical_specialty, Glucose control, type 1 diabetes, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, insulin analogues, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pharmacokinetics, Internal medicine, Internal Medicine, medicine, pharmacodynamics, randomized trial, Humans, Hypoglycemic Agents, Insulin, In patient, Type 1 diabetes, Cross-Over Studies, Insulin Lispro, business.industry, Original Articles, medicine.disease, Crossover study, Postprandial, glycaemic control, Diabetes Mellitus, Type 1, Glucose, Original Article, Insulin absorption, business, pharmacokinetics

الوصف: Aims To compare the pharmacokinetic (PK) and glucodynamic (GD) characteristics of ultra rapid lispro (URLi; Eli Lilly and Company, Indianapolis, Indiana), Fiasp® (Novo Nordisk, Bagsvaerd, Denmark), Humalog® (Eli Lilly and Company) and NovoRapid® (Novo Nordisk), in patients with type 1 diabetes (T1D). Materials and Methods This was a randomized, double‐blind, four‐period, crossover study, conducted in 68 patients with T1D. Patients received the same individualized subcutaneous dose of each study drug immediately prior to a liquid test meal. For comparison, 12 healthy subjects received the same test meal. Results URLi had a significantly faster insulin absorption compared to the other insulins tested. Early half‐maximal drug concentration was reached 13 minutes after administration of URLi, which was 6 minutes faster than Fiasp, 13 minutes faster than Humalog, and 14 minutes faster than NovoRapid (all P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5389cfce7345fb4921d7a00fbf48d12cTest
http://europepmc.org/articles/PMC7540588Test

المؤلفون: Christoph Kapitza, Lenore Teichert, Irene Nowotny, Leszek Nosek, Wolfgang Schmider

المصدر: Diabetes Technology & Therapeutics

مصطلحات موضوعية: Adult, Blood Glucose, Male, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Pharmacology, Insulin aspart, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, Pharmacokinetics, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, European Union, 030212 general & internal medicine, Biosimilar Pharmaceuticals, Aged, Type 1 diabetes, Cross-Over Studies, business.industry, Biosimilar, nutritional and metabolic diseases, Original Articles, Middle Aged, medicine.disease, United States, Phase i study, Medical Laboratory Technology, Diabetes Mellitus, Type 1, Treatment Outcome, Pharmacodynamics, Phase I study, Glucose Clamp Technique, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug

الوصف: Background: The objective of this study was to demonstrate the pharmacokinetic and pharmacodynamic similarity among SAR341402 insulin aspart biosimilar/follow-on product, United States-sourced insulin aspart (NovoLog®), and European Union-sourced insulin aspart (NovoRapid®). Materials and Methods: This was a single-center, randomized, double-blind, 3-treatment, 3-period, single-dose, crossover euglycemic study (NCT03202875) in 30 adult male subjects with type 1 diabetes (T1D). Subjects received 0.3 U/kg of each treatment under fasted conditions and underwent a 12-h euglycemic clamp technique to assess pharmacokinetic and pharmacodynamic activity for up to 12 h. Primary endpoints were area under the plasma insulin concentration–time curve from time zero to the last quantifiable concentration (INS-AUClast), and extrapolated to infinity (INS-AUCinf), maximum plasma insulin concentration (INS-Cmax), and the area under the body weight-standardized glucose infusion rate (GIR)–time curve from 0 to 12 hours (GIR-AUC0–12h) among the three treatments. GIRmax was the main secondary endpoint. Results: Of the 30 subjects randomized, 29 completed all 3 treatment periods. Pharmacokinetic and pharmacodynamic profiles were similar in all groups. The extent of exposure (INS-Cmax, INS-AUClast, and INS-AUCinf) and glucodynamic activity (GIR-AUC0–12h, GIRmax) was similar among the three treatments. The corresponding 90% confidence intervals for pairwise treatment ratios were completely contained within the limits of 80%–125%. SAR341402 was well tolerated. Conclusions: The present study demonstrated similar pharmacokinetic exposure profiles and glucodynamic potency among SAR341402, NovoLog, and NovoRapid in subjects with T1D, supporting further clinical evaluation of SAR341402 as a biosimilar/follow-on product.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::835b87dcd9ea09245d748d78b896ec2bTest
https://doi.org/10.1089/dia.2019.0351Test