Phase IIIb, randomized, multicenter, double-blind, prospective study to evaluate the efficacy and safety of a daily fixed-dose combination of glimepiride / vildagliptin / metformin in patients with type 2 diabetes with a history of dual treatment failure and combined or individual oral antidiabetics with SGLT2 / Metformin, Biguanide / Sulfonylurea, Sulfonylurea / iDPP4 or Biguanide / iDPP4. To evaluate the changes in the percentage of HbA1c at 3 and 6 months with regard to their baseline measurement.

开始日期2023-03-21

申办/合作机构

Laboratorios Silanes SA de CV

100 项与格列美脲/维格列汀/盐酸二甲双胍相关的临床结果

登录后查看更多信息

100 项与格列美脲/维格列汀/盐酸二甲双胍相关的转化医学

登录后查看更多信息

100 项与格列美脲/维格列汀/盐酸二甲双胍相关的专利（医药）

登录后查看更多信息

项与格列美脲/维格列汀/盐酸二甲双胍相关的文献（医药）

2023-06-12·Journal of chemical information and modeling

Molecular Generation with Reduced Labeling through Constraint Architecture.

Article

作者: Wang, Mingyang ; Hsieh, Chang-Yu ; Cao, Dongsheng ; Hou, Tingjun ; Jin, Ruofan ; Sun, Huiyong ; Wang, Jike ; Chen, Xi ; Zhang, Xujun ; Zeng, Yundian ; Wang, Xiaorui ; Wang, Junmei

In the past few years, a number of machine learning (ML)-based molecular generative models have been proposed for generating molecules with desirable properties, but they all require a large amount of label data of pharmacological and physicochemical properties. However, experimental determination of these labels, especially bioactivity labels, is very expensive. In this study, we analyze the dependence of various multi-property molecule generation models on biological activity label data and propose Frag-G/M, a fragment-based multi-constraint molecular generation framework based on conditional transformer, recurrent neural networks (RNNs), and reinforcement learning (RL). The experimental results illustrate that, using the same number of labels, Frag-G/M can generate more desired molecules than the baselines (several times more than the baselines). Moreover, compared with the known active compounds, the molecules generated by Frag-G/M exhibit higher scaffold diversity than those generated by the baselines, thus making it more promising to be used in real-world drug discovery scenarios.

2023-06-01·International Journal of Biological Macromolecules

The reason and mechanism of propylene glycol alginate sodium sulfate (PSS) mediated allergic side effect

Article

作者: Xin, Meng ; He, Xiao-Xi ; Li, Chun-Xia ; Jiang, Xin-Yang ; Li, Hai-Hua ; Yu, Guang-Li ; Li, Shuang ; Xue, Yi-Ting

Propylene glycol alginate sodium sulfate (PSS) is a heparinoid polysaccharide drug used in clinic for >30 years in China. But its allergy events happened from time to time and should not be ignored. Here, ammonium salt in PSS (PSS-NH₄⁺), PSS fractions with high Mw (PSS-H-Mw) and low mannuronic acid (M) to guluronic acid (G) ratio (PSS-L-M/G) were found to induce allergic response by the structure-activity and impurity-activity relationships in vitro. Furthermore, we confirmed the reason and elucidated the mechanism accounted for allergic side effect of PSS in vivo. It was found that high IgE levels in PSS-NH₄⁺ and PSS-H-Mw groups upregulate the cascade expression of Lyn-Syk-Akt or Erk and second messenger Ca²⁺, which accelerated mast cells (MCs) degranulation to release histamine, LTB4, TPS, and finally induced lung tissue injury. PSS-L-M/G caused a mild allergic symptom because it only enhanced the expression of p-Lyn and histamine release. In brief, PSS-NH₄⁺ and PSS-H-Mw were main reasons to result in allergic response. Our results suggested that it is very necessary to control the range of Mw and the content of impurities (< 1 % ammonium salt) of PSS to guarantee its safety and effectiveness in clinical treatment.

2021-09-01·Diabetes Care1区 · 医学

Effect of Medical and Surgical Interventions on α-Cell Function in Dysglycemic Youth and Adults in the RISE Study

1区 · 医学

Article

作者: Chisholm, Robin ; Atkinson, Karen M. ; Pierpont, Bridget ; Mather, Kieren J. ; Edelstein, Sharon L. ; Hill, Dave ; Pratt, Linda ; Martinez, Mayra ; Nayak, Krishan ; Barengolts, Elena ; Rue, Abby ; Gross, Susan ; Caprio, Sonia ; Beale, Elizabeth ; Miller, M. Annette ; Savage, Peter J. ; Hendee, Fadi N. ; Wang, Xinhui ; Nadeau, Kristen J. ; Hannon, Tamara S. ; Kahn, Steven E. ; Gebremedhin, Tsige ; Lteif, Amale ; Utzschneider, Kristina M. ; Zeitler, Philip S. ; Green, Melanie Cree ; Leschek, Ellen W. ; Morse, Emily J. ; Lachin, John M. ; Marcovina, Santica ; Kozedub, Alexandra ; Montgomery, Cortney ; Brown, Kathleen ; Xiang, Anny H. ; Albers, John ; Williams, Jayne ; Arslanian, Silva A. ; Ehrmann, David A. ; Palmer, Jerry P. ; Harting, Jessica ; Hogan, Ashley N. ; Kernan-Schloss, Abigail ; Sam, Susan ; Garcia Reyes, Yesenia ; Montgomery, Brenda K. ; Pirics, Vivian ; Temple, Karla A. ; Vissat, Krista ; Porter, Kristin ; Trigo, Enrique ; Moore, Karen ; Van Cauter, Eve ; Guerra, Nancy ; Buchanan, Thomas A. ; Patel, Aniket ; Garrett, Tammy ; Katkhouda, Namir ; Savoye, Mary ; Mokhlesi, Babak

OBJECTIVETo compare effects of medications and laparoscopic gastric band surgery (LB) on α-cell function in dysglycemic youth and adults in the Restoring Insulin Secretion (RISE) Study protocols.RESEARCH DESIGN AND METHODSGlucagon was measured in three randomized, parallel, clinical studies: 1) 91 youth studied at baseline, after 12 months on metformin alone (MET) or glargine followed by metformin (G/M), and 3 months after treatment withdrawal; 2) 267 adults studied at the same time points and treated with MET, G/M, or liraglutide plus metformin (L+M) or given placebo (PLAC); and 3) 88 adults studied at baseline and after 12 and 24 months of LB or MET. Fasting glucagon, glucagon suppression by glucose, and acute glucagon response (AGR) to arginine were assessed during hyperglycemic clamps. Glucagon suppression was also measured during oral glucose tolerance tests (OGTTs).RESULTSNo change in fasting glucagon, steady-state glucagon, or AGR was seen at 12 months following treatment with MET or G/M (in youth and adults) or PLAC (in adults). In contrast, L+M reduced these measures at 12 months (all P ≤ 0.005), which was maintained 3 months after treatment withdrawal (all P < 0.01). LB in adults also reduced fasting glucagon, steady-state glucagon, and AGR at 12 and 24 months (P < 0.05 for all, except AGR at 12 months [P = 0.098]). Similarly, glucagon suppression during OGTTs was greater with L+M and LB. Linear models demonstrated that treatment effects on glucagon with L+M and LB were largely associated with weight loss.CONCLUSIONSGlucagon concentrations were reduced by L+M and LB in adults with dysglycemia, an effect principally attributable to weight loss in both interventions.

100 项与格列美脲/维格列汀/盐酸二甲双胍相关的药物交易

登录后查看更多信息