Read by QxMD icon Read


Feng Peng, Yonggang Chen, Cheng-Yi Chen, Peter G Dormer, Amude Kassim, Mark McLaughlin, Robert A Reamer, Edward C Sherer, Zhiguo Jake Song, Lushi Tan, Matthew T Tudge, Baoqiang Wan, John Y L Chung
A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting group- and precious metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael-lactolization-dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade...
August 4, 2017: Journal of Organic Chemistry
Mitsuyoshi Takahara, Toshihiko Shiraiwa, Naoto Katakami, Taka-Aki Matsuoka, Iichiro Shimomura
No abstract text is available yet for this article.
August 16, 2017: Current Medical Research and Opinion
Shiyao Xu, Dan Tatosian, Ian Mcintosh, Maria Caceres, Catherine Matthews, Koppara Samuel, Diana Selverian, Sanjeev Kumar, Eunkyung Kauh
1. Omarigliptin (MARIZEV®) is a once-weekly DPP-4 inhibitor approved in Japan for the treatment of type 2 diabetes. The objective of this study was to investigate the absorption, metabolism and excretion of omarigliptin in humans. 2. Six healthy subjects received a single oral dose of 25 mg (2.1 µCi) [(14)C]omarigliptin. Blood, plasma, urine and fecal samples were collected at various intervals for up to 20 days post-dose. Radioactivity levels in excreta and plasma/blood samples were determined by accelerator mass spectrometry (AMS)...
June 30, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Ira Gantz, Taro Okamoto, Yuka Ito, Asako Sato, Kotoba Okuyama, Edward A O'Neill, Samuel S Engel, Eseng Lai
INTRODUCTION: Daily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.) orally administered DPP-4 inhibitor might be an appropriate therapeutic option for some patients. METHODS: A 52-week trial was conducted to assess the safety and tolerability (primary objectives) and glycemic efficacy (secondary objectives) of the q...
August 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Yehuda Handelsman, Brett Lauring, Ira Gantz, Carol Iredale, Edward A O'Neill, Ziwen Wei, Shailaja Suryawanshi, Keith D Kaufman, Samuel S Engel, Eseng Lai
OBJECTIVE: To evaluate the efficacy and safety of adding the once-weekly DPP-4 inhibitor omarigliptin or the sulfonylurea glimepiride to the treatment regimen of patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy. METHODS: Patients with T2DM and HbA1c ≥6.5% to ≤9.0% while on a stable dose of metformin (≥1500 mg/day) were randomized to omarigliptin 25 mg once-weekly (N = 376) or glimepiride up to 6 mg once-daily (N = 375) for 54 weeks...
May 26, 2017: Current Medical Research and Opinion
R Ravi Shankar, Silvio E Inzucchi, Victoria Scarabello, Ira Gantz, Keith D Kaufman, Eseng Lai, Paulette Ceesay, Shailaja Suryawanshi, Samuel S Engel
OBJECTIVE: To examine the efficacy and safety of the once-weekly (q.w.) dipeptidyl peptidase-4 inhibitor, omarigliptin, in patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy. METHODS: In a randomized, double-blind trial, patients with T2DM on a stable dose of metformin monotherapy (≥1500 mg/day) with glycated hemoglobin (HbA1c) of 7.0% to 10.5% were randomized to omarigliptin 25 mg q.w. or matching placebo (N = 201 in both) for 24 weeks (primary timepoint) followed by an additional 80-week treatment period...
May 26, 2017: Current Medical Research and Opinion
Ira Gantz, Taro Okamoto, Yuka Ito, Kotoba Okuyama, Edward A O'Neill, Keith D Kaufman, Samuel S Engel, Eseng Lai
AIMS: To assess the safety and efficacy of omarigliptin in Japanese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In a 24-week double-blind trial, 414 patients with T2D were randomized to omarigliptin 25 mg once-weekly (q.w.), sitagliptin 50 mg once daily (q.d.) or placebo. The double-blind period was followed by a 28-week open-label extension during which all patients received omarigliptin 25 mg q.w. Efficacy endpoints were HbA1c, 2-hour post-meal glucose (PMG) and fasting plasma glucose (FPG)...
April 27, 2017: Diabetes, Obesity & Metabolism
Antonio Chacra, Ira Gantz, Geraldine Mendizabal, Lucila Durlach, Edward A O'Neill, Zachary Zimmer, Shailaja Suryawanshi, Samuel S Engel, Eseng Lai
AIMS: To assess the safety and efficacy of omarigliptin in subjects with type 2 diabetes mellitus (T2DM) and chronic renal impairment (RI). METHODS: Patients with T2DM with moderate RI (estimated glomerular filtration rate [eGFR] ≥30 to <60 mL/min/1.73 m(2) ) (N=114), severe RI (eGFR <30 mL/min/1.73 m(2) ) (N=55) or end-stage renal disease on dialysis (N=44), who were either not on an antihyperglycaemic agent therapy for at least 12 weeks at screening, washed-off of oral antihyperglycaemic agent monotherapy or low-dose dual combination therapy, or on insulin monotherapy, with baseline glycated haemoglobin (HbA1c) of 6...
April 27, 2017: International Journal of Clinical Practice
Dimitrios Stoimenis, Thomas Karagiannis, Anastasia Katsoula, Eleni Athanasiadou, Kyriakos Kazakos, Eleni Bekiari, David R Matthews, Apostolos Tsapas
OBJECTIVE: To assess the efficacy and safety of omarigliptin and trelagliptin, novel dipeptidyl peptidase-4 inhibitors administered once-weekly (DPP-4i QW). METHODS: We systematically searched for placebo- and active-controlled randomized trials in adults with type 2 diabetes mellitus. RESULTS: Fifteen primary studies with 5709 participants were included. DPP-4i QW were more effective than placebo in reducing hemoglobin A1c (HbA1c) (Weighted Mean Difference (WMD) -0...
June 2017: Expert Opinion on Pharmacotherapy
Meng-Fang Li, Xiao-Xia Hu, Ai-Qun Ma
Omarigliptin is a novel long-acting DPP-4 inhibitor used for the treatment of T2DM. In this work, a sensitive and selective UHPLC-MS/MS method was developed and validated for determination of omarigliptin in rat plasma. Sample preparation was performed by protein precipitation with acetonitrile. Chromatographic separation of analytes was achieved on a RRHD Eclipse Plus C18 column (2.1 × 50 mm, 1.8 µ), using gradient mobile phase (0.1% formic acid-acetonitrile) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode, with target fragment ions m/z 399...
March 19, 2017: Biomedical Chromatography: BMC
Yuka Ito, Masahiko Mori, Yuki Matsumoto, Taro Okamoto
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Ronald Goldenberg, Ira Gantz, Paula J Andryuk, Edward A O'Neill, Keith D Kaufman, Eseng Lai, Yin Na Wang, Shailaja Suryawanshi, Samuel S Engel
AIM: To compare the efficacy and safety of the once-weekly oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes (T2DM) and inadequate glycaemic control on metformin. MATERIALS AND METHODS: Patients with T2DM with a glycated haemoglobin (HbA1c) concentration ≥6.5% to ≤9.0% while on a stable dose of metformin (≥1500 mg/d) were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 322) or sitagliptin 100 mg once daily (n = 320)...
March 2017: Diabetes, Obesity & Metabolism
Daniel A Tatosian, Nadia Cardillo Marricco, Xiaoli Shirley Glasgow, Bruce DeGroot, Katherine Dunnington, Laura George, Isaias Noel Gendrano, Amy O Johnson-Levonas, Dennis Swearingen, Eunkyung Kauh
Omarigliptin is a dipeptidyl peptidase-4 inhibitor being developed as a once-weekly treatment for type 2 diabetes. This double-blind, double-dummy, randomized, 3-period balanced crossover study definitively evaluated the effects of a supratherapeutic omarigliptin dose on QTc interval. Population-specific correction of QT interval (QTcP) was used for the primary analysis. Healthy subjects (n = 60) were enrolled and received treatments separated by a ≥4-week washout: (1) single-dose 25 mg omarigliptin (day 1), single-dose 175 mg omarigliptin (day 2); (2) placebo (day 1) followed by single-dose 400 mg moxifloxacin (day 2); (3) placebo (days 1 and 2)...
September 2016: Clinical Pharmacology in Drug Development
Carol Addy, Daniel A Tatosian, Xiaoli S Glasgow, Isaias Noel Gendrano Iii, Christine McCrary Sisk, Eunkyung A Kauh, S Aubrey Stoch, John A Wagner
Omarigliptin is being developed as a potent, once-weekly, oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes. This double-blind, randomized, placebo-controlled study evaluated the effects of age, sex, and obesity on the pharmacokinetics of omarigliptin in healthy subjects. A single oral dose of omarigliptin 10 mg (n = 6/panel) or placebo (n = 2/panel) was administered in the fasted state to elderly nonobese men and women, young obese (30 ≤ body mass index [BMI] ≤ 35 kg/m(2) ) men and women, and young nonobese women of nonchildbearing potential...
September 2016: Clinical Pharmacology in Drug Development
Philip M S Evans, Stephen C Bain
INTRODUCTION: The estimated global prevalence of diabetes mellitus for adults aged 20-70 in 2015 was 415 million with approximately 90% of diagnosed cases being Type 2 diabetes mellitus (T2DM). Improvements in lifestyle and effective therapies are key to management but due to the progressive nature of T2DM, pharmacotherapy is typically required. Whilst the initial therapy will usually be with metformin, thereafter treatment should be individualised, with consideration of several different second line options...
October 2016: Expert Opinion on Pharmacotherapy
Shiliang Li, Hongling Xu, Shichao Cui, Fangshu Wu, Youli Zhang, Mingbo Su, Yinghui Gong, Shaobing Qiu, Qian Jiao, Chun Qin, Jiwei Shan, Ming Zhang, Jiawei Wang, Qiao Yin, Minghao Xu, Xiaofeng Liu, Rui Wang, Lili Zhu, Jia Li, Yufang Xu, Hualiang Jiang, Zhenjiang Zhao, Jingya Li, Honglin Li
Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 ≈ 2...
July 28, 2016: Journal of Medicinal Chemistry
Xueying Tan
Omarigliptin is a new once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of type 2 diabetes. It is indicated to have favorable effects on glycosylated hemoglobin (HbA1c), fasting and postmeal plasma glucose. It potently but reversibly inhibits DPP-4 enzyme, which prolongs the circulating half-life of glucagon-like peptide-1 that increases insulin secretion in a glucose-dependent manner. Benefiting from glucose-dependent insulin secretion, omarigliptin is associated with low risk of hypoglycemia...
October 2016: Endocrine
Sumei Ren, Donald Gauthier, Rosemary Marques, Roy Helmy, David Hesk
An efficient synthesis for [(14) C]Omarigliptin (MK-3102) is described. The initial synthesis of a key (14) C-pyrazole moiety did not work due to the lack of stability of (14) C-DMF-DMA reagent. Thus, a new radiolabeled synthon, (14) C-biphenylmethylformate, was synthesized from (14) C-sodium formate in one step in 92% yield and successfully used in construction of the key (14) C-pyrazole moiety. Regioselective N-sulfonation of the pyrazole moiety was achieved through a dehydration-sulfonation-isomerization sequence...
August 2016: Journal of Labelled Compounds & Radiopharmaceuticals
Rajesh Krishna, Carol Addy, Daniel Tatosian, Xiaoli S Glasgow, Isaias Noel Gendrano Iii, Martine Robberechts, Wouter Haazen, J N de Hoon, Marleen Depré, Ashley Martucci, Joanna Z Peng, Amy O Johnson-Levonas, John A Wagner, S Aubrey Stoch
The pharmacokinetics (PK) and pharmacodynamics (PD) of omarigliptin, a novel once-weekly DPP-4 inhibitor, were assessed following single and multiple doses in healthy subjects. Absorption was rapid, and food did not influence single-dose PK. Accumulation was minimal, and steady state was reached after 2 to 3 weeks. Weekly (area under the curve) AUC and Cmax displayed dose proportionality within the dose range studied at steady state. The average renal clearance of omarigliptin was ∼2 L/h. DPP-4 inhibition ranged from ∼77% to 89% at 168 hours following the last of 3 once-weekly doses over the dose range studied...
December 2016: Journal of Clinical Pharmacology
Sanjay Kalra, Yashdeep Gupta
This article introduces the concept of "weekend therapy", which has now become reality in diabetes. It briefly describes injectable and oral drugs which are currently available, or are in advanced stages of development, for use in once weekly administration. These include dulaglutide, exenatide QW, semaglutide, omarigliptin and trelagliptin.
May 2016: JPMA. the Journal of the Pakistan Medical Association
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"