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Objective:To investigate the effect of alogliptin on bone loss in ovariectomized(OVX)mice.Methods:For animal experiments, thirty 8-week-old C57BL/6J female mice were divided into Sham group, OVX group, and OVX+ alogliptin group. OVX+ alogliptin group were administered with alogliptin in a dosage of 20 mg·kg -1·d -1 by gavage, Sham and OVX groups with equivalent saline. After 12 weeks intervention, serum bone anabolism indicators were detected, and Micro CT and HE staining were used to observe and analyze the bone trabecular structure of femur and tibia in mice. For in vitro experiments, bone marrow mesenchymal stem cells(BMSCs)were incubated with 100 μmol/L alogliptin for osteoblast differentiation. Alkaline phosphatase(ALP)and alizarin red S staining were used to determine the ALP activity and mineralization after osteogenic induction and culture. Real-time fluorescence quantitative PCR and Western blot were used to detect mRNA and protein expressions of osteoblast related genes. Results:Alogliptin intervention improved the biochemical indexes of bone anabolism and protected against bone microstructure deterioration to alleviate bone loss in OVX mice. Alogliptin stimulated osteoblast differentiation and elevated expression levels of Runt-related transcription factor 2(Runx2), ALP, osteocalcin, and osterix in in vitro experiments. Conclusion:Alogliptin can alleviate bone loss in OVX mice.
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@#By silica gel column chromatography, solvent extraction and preparative high performance liquid chromatography (HPLC), four new related substance were isolated and purified from the mass production and preparation process of alogliptin benzoate. Then it was analyzed and confirmed by various spectrum identification methods such as nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HR-MS) and Fourier-transform infrared spectroscopy (FTIR) according to its physical and chemical properties. The chemical structures of the four related substances produced in each step of the synthesis process of alogliptin benzoate were determined, and they were named as impurities L, M, T, and V. These four related substances were new impurities which were found for the first time. The isolation and identification of these impurities are of great importance to the quality control of alogliptin benzoate, and the optimization of manufacturing process.
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The objective of the work is to develop and validate a new reverse phased ultra-performance chromatography method and its stability studies for the simultaneous estimation of alogliptin and pioglitazone in bulk and tablet dosage form. The column of the method was BEH C18 (2.1× 50 mm, 1.7 µ) used as a stationary phase and the mobile phase was 45:55 v/v of phosphate buffer (pH 3) and methanol, respectively. The injection volume was 2 µl and flow rate was maintained at 0.3 ml/minute. The wavelength was 280 nm and the runtime was 3 minutes. The retention time of alogliptin was 0.4 minutes and pioglitazone was 0.529 minutes. The Linearity of the alogliptin was 6.25–37.5 µg/ml and pioglitazone was 15–90 µg/ml. The newly developed method could be used for the routine analysis of pure drug and its formulations in accordance with the ICH Q2 (R1) guidelines.
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A liquid chromatography-tandem mass spectrophotometric (LC-MS/MS) method was developed for quantification ofAlogliptin in rabbit plasma employing Liquid-Liquid extraction technique. The developed method was validated forspecificity, precision, accuracy, recovery, and stability characteristics. Chromatographic separation was achieved onInertsil ODS 5 µm C18, 50 × 4.60 mm with 30:70 v/v of 0.1% formic acids: Organic Mixture (acetonitrile: methanol,80:20% v/v) as an isocratic mobile phase with a flow rate of 1.0 ml/min. the developed LC-MS method was appliedto assess pharmacokinetics parameters of alogliptin tablet in healthy rabbits. Alogliptin showed Tmax of 2.6 ± 0.37 hand mean Cmax, AUC 0-t and AUC0 for test formulation is 90.6 ± 4.41, 1675.41 ± 164 and 3726.47 ± 796 respectively
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Antihyperglycemic therapies may increase the risk of cardiovascular events. There is a paucity of data evaluating the cardiovascular safety of antihyperglycemic therapies in the high-risk period following an acute coronary syndrome ( ACS ) . This article is the Chinese translation of "Early and chronic dipeptidyl-peptidase-Ⅳinhibition and cardiovascular events in patients with Type 2 diabetes mellitus after an acute coronary syndrome: a Landmark analysis of the EXAMINE" published on Journal of the American Heart Association in May 2018 [ Sharma A, Cannon CP, White WB, et al. J Am Heart Assoc, 2018,7(11). Pii:e007649] with open access. The EXAMINE trial randomized 5380 patients who were 15 to 90 days after ACS to the DPP-Ⅳinhibitor alogliptin versus placebo;mean follow-up was 18 months. The landmark analysis were used to assess the burden of cardiovascular events from randomization to 6 months ( early period ) and from 6 months to the end of follow-up ( late period ) and the risk of cardiovascular events associated with early ( up to 6 months) and chronic ( 6 months to end of follow-up) DPP-Ⅳinhibition with alogliptin. Patients with early versus late events had similar baseline demographic profiles. Overall, 42.1％of the composite of cardiovascular death/myocardial infarction/stroke and 47. 5％ of hospitalization for heart failure occurred in the early period. Early DPP-Ⅳ inhibition with alogliptin did not increase the risk of early cardiovascular death/myocardial infarction/stroke (HR 0.96, 95％CI 0.76-1.21) or hospitalization for heart failure ( HR 1.23, 95％CI 0.84-1.82) . Similarly, chronic DPP-Ⅳinhibition with alogliptin did not increase the risk of late cardiovascular death/myocardial infarction/stroke (HR 1.03, 95％CI 0.89-1.26) or hospitalization for heart failure (hazard ratio 1.02, 95％ CI, 0.85-1.22). Early after an ACS, patients with type 2 diabetes mellitus experience a significant burden of heart failure events and recurrent ACS. DPP-Ⅳinhibition with alogliptin appears to be safe even in the high-risk period following an ACS.
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OBJECTIVE:To evaluate the economical efficiency of alogliptin for type 2 diabetes and provide clinical evi-dence for related researches. METHODS:Retrieved from Cochrane Library,Pubmed,EMBase,CNKI,VIP,Wanfang,CBM database up from the start of the database to Mar.,2014,RCTs about alogliptin combined with traditional antidiabetic agents regimen vs. traditional antidiabetic agents regimen in the treatment of type 2 diabetes mellitus were included. Based on the sec-ondary analysis method of literatures,Effectiveness indexes and treatment course were extracted from the literatures,from the perspective of patients,and daily treatment cost was used to calculate the cost;cost-effectiveness analysis was adopted to evalu-ate the economical efficiency of alogliptin combined with traditional antidiabetic agents regimen vs. traditional antidiabetic agents regimen. RESULTS and CONCLUSIONS:6 literatures which met inclusion criteria were included. When alogliptin com-bined with metformin treatment lasted for 12 weeks,the decrease value of HbA1c as effect index showed poor cost-effective-ness;when treatment course increased to 26 weeks,the rate of qualified HbA1c as effect index showed poor cost-effectiveness. When the price of alogliptin decreased by 10% or the effects of trial group was the upper limit of 95%CI,the cost-effective-ness was superior to metformin regimen group. 12 weeks of alogliptin combined with pioglitazone treatment showed better cost-effectiveness than pioglitazone alone using the decrease value of HbA1c as effect;when treatment course increased to 26 weeks,the treatment showed poor cost-effectiveness;when treatment conrse increased to 26 weeks,using the rate of qualified HbA1c as effect indes,the results of sensitirity analysis showed that cost-effectiveness of trial group was better than that of pio-glitazone alone group as the apper limit of 95% CI. When alogliptin combined voglibose treatment lasted for 12 weeks,the de-crease value of HbA1c as effect index showed superior cost-effectiveness to voglibose regimen group. It is suggested to develop alogliptin pharmacoeconomics research based on RCTs and pharmacoeconomics research about improving diabetes patients’ long-term living quality.
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Alogliptin is a novel dipeptide peptidase-4 inhibitor approved for the treatment of type 2 diabetic mellitus.Numerous clinical studies showed that alogliptin alone or in combination with other oral antidiabetic drugs or insulin can substantially control the level of plasma glucose and glycated hemoglobin (HbA1c) in type 2 diabetic patients.12.5 to 25 mg alogliptin alone once daily reduced HbA1c by 0.56％ to 0.59％ ; while combination with other antidiabetic agents resulted additional HbA1c lowering of 0.4％ to 0.8％.Alogliptin was well tolerated,with low incidence of hypoglycemia and no weight gain.Furthermore,alogliptin displayed no extra cardiovascular risk in patients with cardiovascular diseases.