- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Journal: Enabling biocatalysis in high-concentration organic cosolvent by enzyme gate engineering. (Pubmed Central) - Apr 5, 2022
An R-selective ω-amine transaminase variant (AcATA ) exhibited high activity toward 50 g/L pro-sitagliptin ketone 1-[1-piperidinyl]-4-[2,4,5-trifluorophenyl]-1,3-butanedione (PTfpB)...Molecular dynamic simulations revealed that the increase in DMSO resistance was mainly caused by the decrease in the number of DMSO molecules in the substrate-binding pocket. Moreover, in the kilogram-scale experiment, the conversion of 80 g/L substrate was increased from 50% (AcATA ) to 85% (M2 in 40% DMSO) with a high e.e. of >99% within 24 h.
- |||||||||| Tekturna (aliskiren) / PDL, Januvia (sitagliptin) / Merck (MSD)
Retrospective data, Journal: Identifying congeners and transformation products of organic contaminants within complex chemical mixtures in impacted surface waters with a top-down non-targeted screening workflow. (Pubmed Central) - Apr 1, 2022
Reference standards were used to confirm the identification of 53 contaminants among them lesser-known pharmaceuticals (aliskiren, sitagliptin) and consumer product additives (lauramidopropyl betaine, 2,2,4-trimethyl-1,2-dihydroquinoline)...As such, several previously unknown TPs of pesticides (metolachlor) and pharmaceuticals (gliclazide, irbesartan) were identified as tentative candidates or probable structures...Furthermore, it allows elucidating the structure of TPs directly from samples without relying on bottom-up studies under conditions discussed herein. The top-down workflow and the MNC tools show great potential for data mining and retrospective analysis of previous NTS studies.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Preclinical, Journal: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, attenuates apoptosis of vascular smooth muscle cells and reduces atherosclerosis in diabetic apolipoprotein E-deficient mice. (Pubmed Central) - Mar 26, 2022
Sitagliptin increased GLP-1-induced cytosolic levels of β-catenin compared with GLP-1 alone, resulted in increasing the expression of survivin, and suppressed proinflammatory cytokines, i.e., interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α), production in response to HO. In conclusion, these results indicated that the anti-atherosclerotic effect of sitagliptin is mediated, at least in part, by its inhibition of VSMCs apoptosis.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Trial withdrawal: Sitagliptin in Type I Diabetic Patients (clinicaltrials.gov) - Mar 24, 2022
P=N/A, N=0, Withdrawn,
In conclusion, these results indicated that the anti-atherosclerotic effect of sitagliptin is mediated, at least in part, by its inhibition of VSMCs apoptosis. Terminated --> Withdrawn
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Journal, HEOR: Implications and Economic Impact of Applying International Guidelines and Recommendations to the Management of High-Risk Group of Type 2 Diabetes Mellitus Patients in India. (Pubmed Central) - Mar 23, 2022
Objectives Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase IV (DPP-IV) inhibitors are recommended as preferred add-on oral antidiabetic drugs (OADs) after metformin among type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD)...Upon calculating the ICERs, additional cost to prevent one all-cause death with dapagliflozin substitution is INR 660,020-25,384,369; INR 2,223,326 with empagliflozin substitution and INR 8,069,818 with canagliflozin substitution...Incremental costs for various outcomes were higher with the addition of SGLT-2 inhibitors and significantly more if substitution with sitagliptin/linagliptin was also done...Dapagliflozin, being available as cheaper generic versions, appears to be most effective for most outcomes. Interpretations are subjective in terms of value assigned for preventing a major event.
- |||||||||| Victoza (liraglutide) / Novo Nordisk
LIRAGLUTIDE FOR INSULIN RESISTANCE AFTER BURN INJURY ([VIRTUAL]) - Mar 23, 2022 - Abstract #SCCM2022SCCM_1895;
Liraglutide may be an option to help liberate burn patients from insulin infusions and transition to lower levels of care. Further investigation is warranted.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Journal: Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Sitagliptin phosphate monohydrate. (Pubmed Central) - Mar 17, 2022
In light of its broad therapeutic index and lack of severe adverse effects, the clinical risks associated with moderately supraoptimal doses were deemed inconsequential, as were the risks associated with moderately suboptimal doses. Taking all evidence into consideration, it was concluded that the BCS-based biowaiver can be implemented for solid IR oral drug products containing sitagliptin phosphate monohydrate, provided (a) the test product is formulated solely with excipients commonly present in solid IR oral drug products approved in ICH or associated countries and used in amounts commonly applied in this type of product, (b) data in support of the BCS-based biowaiver are obtained using the methods recommended by the WHO, FDA, EMA or ICH and (c) the test product and the comparator product (which is the innovator product in this case) meet all in vitro dissolution specifications provided in the WHO, FDA, EMA or ICH guidance.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Preclinical, Journal: Sitagliptin's renoprotective effect in a diabetic nephropathy model in rats: The potential role of PI3K/ Akt pathway. (Pubmed Central) - Mar 16, 2022
Taking all evidence into consideration, it was concluded that the BCS-based biowaiver can be implemented for solid IR oral drug products containing sitagliptin phosphate monohydrate, provided (a) the test product is formulated solely with excipients commonly present in solid IR oral drug products approved in ICH or associated countries and used in amounts commonly applied in this type of product, (b) data in support of the BCS-based biowaiver are obtained using the methods recommended by the WHO, FDA, EMA or ICH and (c) the test product and the comparator product (which is the innovator product in this case) meet all in vitro dissolution specifications provided in the WHO, FDA, EMA or ICH guidance. This work shows that sitagliptin improved renal functions and histopathological changes, impeded inflammation, and oxidative stress and upregulated PI3K/AKT pathway which highlights its reno-protective effects in a rat model of DN.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Journal: Repurposing of existing antibiotics for the treatment of diabetes mellitus. (Pubmed Central) - Mar 12, 2022
MD simulations results showed clindamycin as potent virtual hit and suggested that it binds with DPP-4 in competitive manner, which virtually indicate that besides antibiotic activity clindamycin has anti-diabetic activity. The online version contains supplementary material available at 10.1007/s40203-021-00118-6.
- |||||||||| Nesina (alogliptin) / Takeda, Tenelia (teneligliptin) / Daiichi Sankyo, Mitsubishi Tanabe, Januvia (sitagliptin) / Merck (MSD)
Review, Journal: The role of dipeptidyl peptidase-IV in abdominal aortic aneurysm pathogenesis: A systematic review. (Pubmed Central) - Mar 11, 2022
There is an existing translational gap from preclinical observations to clinical trials in this important and novel mechanism of AAA pathogenesis. This prior literature highlights the need for further research on molecular targets involved in AAA formation.
- |||||||||| Suiny (anagliptin) / Kowa, Medca Japan, Januvia (sitagliptin) / Merck (MSD)
Journal: Effect of Anagliptin versus Sitagliptin on Renal Function: Subanalyzes from the REASON Trial. (Pubmed Central) - Mar 11, 2022
The difference in eGFR was affected by the differences in HbA1c level and BP, and the difference in the UACR was affected by the differences in LDL-C level and BP, which were reduced only in the ANA group. These findings imply that the effects of DPP-4 inhibitors on renal function, especially on UACR, may be different between the types of DPP-4 inhibitors.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Journal: Knockdown of DPP4 promotes the proliferation and the activation of the CREB/aromatase pathway in ovarian granulosa cells. (Pubmed Central) - Mar 9, 2022
Additionally, sitagliptin reversed the inhibitory effects caused by GOA‑BSA treatment on the cell cycle progression and on the activation of the CREB/aromatase pathway in KGN cells, as determined by the increased expression levels of the cell cycle‑associated proteins as well as those of the CREB protein and the CYP19A1 and CYP11A1 enzymes. In conclusion, inhibition of DPP4 expression promoted the proliferation of KGN cells and the activation of the CREB/aromatase pathway.
- |||||||||| Implications and Economic Impact of Applying International Guidelines to the Management of High Risk T2DM Patients in India (In-person & Virtual) - Mar 8, 2022 - Abstract #ISPOR2022ISPOR_380;
OBJECTIVES: SGLT-2i’s and DPP-IVi's are recommended as preferred add-on OAD’s after metformin among T2DM patients with ASCVD, HF, CKD...Upon calculating the ICERs, additional cost to prevent one all cause death with dapagliflozin substitution is INR 37,33,220 - 1,43,58,538.5, INR Rs 22,23,326.09 with empagliflozin substitution, and INR 80,69,818.18 with canagliflozin substitution...Incremental costs for various outcomes were further higher with addition of SGLT-2i’s along with substitution with sitagliptin / linagliptin. The incremental costs of prescribing SGLT-2i’s and DPP-IVi's per event reduction are very high for most outcomes considering Indian socioeconomic context; interpretations are subjective in terms of perceived value of an event prevention.
- |||||||||| Victoza (liraglutide) / Novo Nordisk, Januvia (sitagliptin) / Merck (MSD)
Emulating the Grade Trial Using Real-World Data (In-person & Virtual) - Mar 8, 2022 - Abstract #ISPOR2022ISPOR_160;
There were no significant differences among treatment groups for other secondary outcomes. CONCLUSIONS : In this emulation of the GRADE trial, liraglutide was significantly more effective at improving glycemic control than glimepiride or sitagliptin.
- |||||||||| Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim, Januvia (sitagliptin) / Merck (MSD)
Randomized Clinical Trial Replication for Cardiovascular Outcomes of EMPA-Reg Trial: Retrospective Cohort Study (Virtual) - Mar 8, 2022 - Abstract #ISPOR2022ISPOR_140;
P3
We followed-up (median, 2.7 years) 23,126 matched patients with type 2 diabetes mellitus (11,563 empagliflozin users and 11,563 sitagliptin users). Our study results suggest that RWD results can replicate RCT results satisfactorily and have the potential for providing evidence for future regulatory decision-making.
- |||||||||| Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) / Gilead, Januvia (sitagliptin) / Merck (MSD)
Severe Hypomagnesemia in an HIV Patient due to Hepatocyte Nuclear Factor 1B Deletion () - Mar 6, 2022 - Abstract #NKFSCM2022NKF_SCM_674;
Medications included sitagliptin, insulin glargine, metoprolol, atorvastatin, aspirin, clopidogrel and bictegravir-emtricitabine-tenofovir alafenamide...Despite magnesium supplementation and amiloride, he continued to require intermittent intravenous magnesium...Our patient’s long-standing history of hypomagnesemia preceded his diagnosis of diabetes and was his first manifestation of HNF1B-associated kidney disease. This disease is a challenging diagnosis that may not present until adulthood and should be considered in unexplained renal magnesium wasting and features such as diabetes and kidney cysts.
- |||||||||| Daklinza (daclatasvir) / BMS
Preclinical, Journal: Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay. (Pubmed Central) - Mar 5, 2022
Thus, we provide methods for rapid and effective screening and development of inhibitors for blocking virus polyprotein processing as SARS-CoV-2 antivirals. Additionally, we show that the combined inhibition of Mpro and PLpro is more effective in inhibiting SARS-CoV-2 and the delta variant.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Preclinical, Journal: Virtual screening and in vitro assays of novel hits as promising DPP-4 inhibitors. (Pubmed Central) - Mar 3, 2022
Both compounds (ZINC1572309 and the reference drug - sitagliptin) also inhibited DPP-4 activity, suggesting interesting biological effects of the selected compound at non-cytotoxic concentrations. Therefore, from in silico and in vitro studies, a potential hit as DPP-4 inhibitor was discovered and it can be structurally optimized to achieve suitable activity and pharmacokinetic profiles.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Clinical, Journal: Sitagliptin and Narrow-Band Ultraviolet-B for Moderate Psoriasis (DINUP): A Randomised Controlled Clinical Trial. (Pubmed Central) - Feb 26, 2022
Therefore, from in silico and in vitro studies, a potential hit as DPP-4 inhibitor was discovered and it can be structurally optimized to achieve suitable activity and pharmacokinetic profiles. Sitagliptin therapy combined with NB-UVB phototherapy significantly improved psoriasis severity, albeit modestly, compared to NB-UVB phototherapy alone in patients with moderate psoriasis without T2DM.
- |||||||||| Januvia (sitagliptin) / Merck (MSD)
Clinical, Journal: Efficacy and safety profile of Sitagliptin, vildagliptin, and metformin in newly diagnosed type 2 diabetic subjects. (Pubmed Central) - Feb 25, 2022
DPP-4 inhibitors and metformin showed favorable effects on improving metabolic syndrome by decreasing blood pressure, serum triglycerides (TG), low-density lipoprotein (LDL), total cholesterol, and increasing high-density lipoprotein (HDL), plus their positive impacts on weight. As a final conclusion, the three medications are highly comparable.
- |||||||||| Victoza (liraglutide) / Novo Nordisk, Januvia (sitagliptin) / Merck (MSD)
Retrospective data, Journal: Evaluation of the risk of fracture in type 2 diabetes mellitus patients with incretins: an updated meta-analysis. (Pubmed Central) - Feb 23, 2022
Collectively, Sitagliptin ameliorated hypoxia-induced damages in ESCs by suppressing the inflammation. This meta-analysis suggested that the current use of incretins not only is safe for fracture in type 2 diabetes patients from RCT studies, but also, when sitagliptin 100 mg or liraglutide 1.8 mg per day was administered, it may exhibit protective effects on bone metabolism.
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