Efficacy and safety of vildagliptin in clinical practice-results of the PROVIL-study

AIM:To investigate efficacy and safety of vildagliptin compared to other oral antidiabetics in clinical practice in Germany.METHODS:In this prospective,open,observational study,patients with type 2 diabetes mellitus(T2DM) previously on oral monotherapy were selected by their treating physician to receive either vildagliptin addon to metformin(cohort 1),vildagliptin+metformin single-pill combination(SPC)(cohort 2)or another dual combination therapy with oral antidiabetic drugs(OADs)(cohort 3).According to routine clinical practice,interim examinations occurred every 3 mo:at baseline,after approximately 3 mo and after approximately 6 mo.Parameters documented in the study included demographic and diagnostic data,history of T2DM,data on diabetes control,vital signs,relevant prior and concomitant medication and disease history.Efficacy was assessed by changes in HbA1c and fasting plasma glucose(FPG)3 mo and 6 mo after initiation of dual combination therapy.Safety was assessed by adverseevent reporting and measurement of specific laboratory values(serum creatinine,total bilirubin,alanine aminotransferase,aspartate aminotransferase,creatine kinase).RESULTS:Between October 2009 and January 2011,a total of 3881 patients were enrolled in this study.Since 47 patients were withdrawn due to protocol violations,3834 patients were included in the statistical analysis.There were no relevant differences between the three cohorts concerning age,body weight and body mass index.Average diabetes duration was approximately 6 years and mean HbA1c was between 7.6%and 7.9% at baseline.Antidiabetic treatment was recorded in 3648 patients.Patients were treated with vildagliptin add-on to metformin(n=603),vildagliptin+metformin(SPC)(n =2198),and other oral OADs including combinations of metformin with sulfonylurea(n=370),with glitazones(n =123),other dipeptidyl peptidase-4 inhibitors(n=99).After 6 mo of treatment,the absolute decrease in HbA1c(mean±SE)was significantly more pronounced in patients receiving vildagliptin add-on to metformin(-0.9% ±0.04%)and vildagliptin+metformin(SPC)(-0.9%± 0.03%)than in patients receiving other OADs(-0.6% ±0.04%;P<0.0001).In addition,significant cohort differences were observed for the improvement in FPG after 6 mo treatment(vildagliptin add-on to metformin:-291 mg/L±18.3 mg/L;vildagliptin+metformin(SPC):-305 mg/L±9.6 mg/L;other antidiabetic drugs:-209 mg/L±14.0 mg/L for(P<0.0001).Moderate decreases in body weight(absolute difference between last control and baseline:mean±SE)were observed for patients in all cohorts(vildagliptin add-on to metformin:-1.4 kg ±0.17 kg;vildagliptin+metformin(SPC):-1.7 kg± 0.09 kg;other OADs:?0.8 kg±0.13 kg).No significant differences in adverse events(AEs)and other safety measures were observed between the cohorts.When performing an additional analysis by age(patients<65 years vs patients≥65 years),there was no relevant difference in the most common AEs between the two age groups and the AE profile was similar to that of the overall patient population.CONCLUSION:Clinical practice confirms that vildagliptin is an effective and well-tolerated treatment in combination with metformin in T2DM patients.

Effect of vildagliptin as add-on therapy to a low-dose metformin

AIM:To evaluate the efficacy and safety of the addition of vildagliptin to low-dose metformin and compare it to an uptitration of metformin in type 2 diabetes mellitus(T2DM) patients who have inadequate control with metformin monotherapy.METHODS:Eligible patients were randomized to receive vildagliptin 100 mg qd or metformin(500 mg qd for 2 wk and then 500 mg bid) added to open label me tformin 500 mg bid for the 24 wk.The primary endpoi nt was baseline to endpoint hemoglobin A1c(HbA1c) change.RESULTS:The adjusted mean change from baseline in HbA1c at the 24th wk was-0.51% in the vildagliptin/metformin group(mean baseline HbA1c:7.4%) and-0.37% in the metformin monothera py group(mean baseline HbA1c:7.3%).The mean diffe rence was-0.14% with 95% Confidence Interval(-0.24%,-0.05%).As non-inf e riority(margin of 0.4%) was achieved,a test for superiority was performed.This test showed statistically significant superiority of the combination over monotherapy group(P = 0.002).Gastrointestinal(GI) adverse events were signif icantly more frequent in the metformin group than the combin ation group(21.0% vs 15.4%,P = 0.032).CONCLUSION:In patients with T2DM inadequately controlled with metformin up to 1000 mg daily,the addition of vildagliptin 100 mg daily achieved larger HbA1c reduction with fewer GI events than with increa sing the metformin dose.

Vildagliptin-insulin combination improves glycemic control in Asians with type 2 diabetes

AIM: To assess the efficacy and safety of vildagliptin 50 mg bid as add-on therapy to insulin in Asian patients with type 2 diabetes mellitus(T2DM).METHODS: This was a post hoc analysis of a subgroup of Asian patients from a multicenter,randomized,double-blind,placebo-controlled,parallel-group study in T2DM patients inadequately controlled by stable insulin therapy,with or without metformin.A total of 173 patients were randomized 1:1 to receive treatment with vildagliptin 50 mg bid(n = 87) or placebo(n = 86) for 24 wk.Changes in HbA1c and fasting plasma glucose(FPG),from baseline to study endpoint,were analyzed using an analysis of covariance model.Change from baseline to endpoint in body weight was summarized by treatment.Safety and tolerability of vildagliptin was also evaluated.RESULTS: After 24 wk,the difference in adjusted mean change in HbA1c between vildagliptin and placebo was 0.82%(8.96 mmol/mol;P < 0.001) in Asian subgroup,0.85%(9.29 mmol/mol;P < 0.001) in patients also receiving metformin,and 0.73%(7.98 mmol/mol;P < 0.001) in patients without metformin,all in favor of vildagliptin.There was no significant difference in the change in FPG between treatments.Weight was stable in both treatment groups(+0.3 kg and-0.2 kg,for vildagliptin and placebo,respectively).Overall,vildagliptin was safe and well tolerated with similarly low incidences of hypoglycemia(8.0% vs 8.1%) and no severe hypoglycemic events were experienced in either group.CONCLUSION: In Asian patients inadequately controlled with insulin(with or without concomitant metformin),insulin-vildagliptin combination treatment significantly reduced HbA1c compared with placebo,without an increase in risk of hypoglycemia or weight gain.

Efficacy and safety of vildagliptin/pioglitazone combination therapy in Korean patients with diabetes

AIM:To assess the efficacy and safety of vildagliptin/pioglitazone combination therapy in Korean patients with type 2 diabetes mellitus(T2DM).METHODS:This was a post hoc analysis in Korean patients,from a 24-wk,randomized,active-controlled,double-blind,parallel-group,multicenter study.Eligible patients were aged between 18 and 80 years,drug naive,and had been diagnosed with T2DM [hemoglobin A1c(HbA1c):7.5-11.0 and fasting plasma glucose(FPG):【 270 mg/dL(【 15 mmol/L)].Patients were randomized(1:1:1:1) to receive the vildagliptin/pioglitazone comb ination at 100/30 mg q.d.(high-dose) or 50/15 mg q.d.(low-dose),vildagliptin 100 mg q.d.,or pioglitazone 30 mg q.d.monotherapies.The primary outcome measure was change in HbA1c from baseline to endpoint.RESULTS:The distribution of baseline demographic and clinical parameters was well balanced between treatment groups.The overall mean age,body mass index,HbA1c,FPG,and duration of disease were 50.8 years,24.6 kg/m2,8.6,10.1 mmol/L,and 2.2 years,respectively.Adjusted mean changes(± standard error) in HbA1c from baseline(~8.7) to week 24 endpoint were-2.03 ± 0.16(high-dose,N = 34),-1.88 ± 0.15(low-dose,N = 34),-1.31 ± 0.21(vildagliptin,N = 36),and-1.52 ± 0.16(pioglitazone,N = 36).The high-dose combination therapy demonstrated greater efficacy than monotherapies [vildagliptin(P = 0.029) and pioglitazone(P = 0.027)].Percentage of patients achieving HbA1c 【 7 and ≤ 6.5 was the highest in the high-dose group(76 and 68) followed by low-dose(58 and 47),vildagliptin(59 and 37),and pioglitazone(53 and 28) groups.The overall incidence of adverse events was comparable.CONCLUSION:In Korean patients,first-line treatment with high-dose combination therapy improved glycemic control compared to pioglitazone and vildagliptin monotherapies,consistent with results published for the overall study population.

Short-Term Effects of Liraglutide versus Vildagliptin on Insulin Secretion and Sensitivity in Type 2 Diabetes: A Single Blinded Randomized Controlled Trial (LIRAVIS Study)

Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized controlled single blinded clinical trial in 14 uncontrolled type 2 diabetes patients (HbA1c ≥ 53 mmol/mol) with mean duration of diabetes of 8 [1 - 12] years and median age of 57 [49 - 61] years. Baseline treatment consisted of metformin in monotherapy or metformin plus sulfonylureas. Participants were randomly allocated to 2 groups of add-on 1.2 mg/day subcutaneous liraglutide in group 1 or 100 mg/day of oral vildagliptin in group 2 for 2 weeks. In all participants, insulin secretion in response to mixed meal tolerance test, insulin sensitivity by 80 mU/m2/min hyperinsulinemic-euglycemic clamp, body composition, and lipid profile were measured before and after intervention. Results: At the end of intervention, insulin sensitivity remained unchanged both with liraglutide from 6.6 [4.2 - 7.9] to 6.9 [4.3 - 10.8] mg/kg/min;p = 0.61 and vildagliptin from 7.1 [5.3 - 9.0] to 6.5 [5.6 - 9.4] mg/kg/min (p = 0.86). The area under the C-peptide curve varied from 5.5 [1.0 - 10.9] to 14.9 [10.8 - 17.2] nmol/L/120min, p = 0.09 in group 1 and from 1.1 [0.5 - 14.1] to 13.0 [9.6 - 16.9] nmol/L/120min (p = 0.17) in group 2. LDL Cholesterol levels decreased significantly with liraglutide from 0.85 g/L [0.51 - 1.02] to 0.54 g/L [0.50 - 0.73] (p = 0.04) but not with Vildagliptin. Body weight tended to decrease in group 1 (−0.6 kg) versus modest increase in group 2 (+1.1 kg). Conclusion: Short-term metabolic effects of Liraglutide and Vildagliptin add-on therapy are comparable in sub-Saharan type 2 diabetes patients with a more favorable trend for Liraglutide on body weight, lipid profile, and insulin secretion.

Vildagliptin vs sulfonylurea in Indian Muslim diabetes patients fasting during Ramadan

AIM:To compare the use of vildagliptin and sulfonylurea with or without metformin in Indian Muslim patients with type 2 diabetes mellitus,fasting during Ramadan.METHODS:This was a 4-wk,multicenter,non-interventional,open-label,observational study.Incidence of hypoglycemic events(HEs),adverse events,and changes in glycosylated hemoglobin A1c(HbA1c),fasting plasma glucose,postprandial plasma glucose and body weight were measured pre-and post-Ramadan.RESULTS:Totally,97 patients were recruited and all completed the study(vildagliptin group,n=55;sulfonylurea group,n=42).HEs were reported in low frequencies in both the vildagliptin and the sulfonylurea groups[0 vs 2(4.8%)patients,respectively].Interestingly,HbA1c reduced by-0.43%(-4.71 mmol/mol)in the vildagliptin group[8.75%(72.10 mmol/mol)to8.32%(67.38 mmol/mol),P=0.009]while in the sulfonylurea group there was a small increase by 0.01%[0.08 mmol/mol;8.64%(70.92 mmol/mol)to 8.65%(71.00 mmol/mol),P=0.958].Higher percentage of vildagliptin-treated patients achieved HbA1c<7.0%(<53 mmol/mol)compared with sulfonylurea(16.4%vs4.8%).Mean decrease in the body weight was 1.2 kg and 0.03 kg,respectively(P<0.001).Both treatment groups were well tolerated during Ramadan.CONCLUSION:Vildagliptin is an attractive treatment option for Indian patients with type 2 diabetes mellitus who are fasting during Ramadan.

Mechanism Based Pharmacokinetic Pharmacodynamic Modeling of Vildagliptin as an Add-on to Metformin for Subjects with Type 2 Diabetes

Various drugs are used to maintain normoglycemia in subjects with type 2 diabetes mellitus.The combination of the drugs from different classes in one single tablet may enhance the effectiveness of the anti-diabetic drugs.To investigate the impact of combining drugs on the glucose regulation of subjects with type 2 diabetes,we propose a pharmacokinetic/pharmacodynamics(PK/PD)mathematical modeling approach for a combination of metformin and vildagliptin drugs.In the proposed modeling approach,two separate PK models representing oral administration of metformin and vildagliptin for diabetic subjects are interconnected to a PD model comprising a detailed compartmental physiological model representing the regulatory effect of insulin,incretins and glucagon hormones on glucose concentration in a human body.The impact of doses of individual drugs and their combination on the blood glucose concentration of a group of type 2 diabetic subjects is investigated.It is indicated that while administration of individual drugs reduces the blood glucose levels,since they have separate mechanisms of action,combining them synergizes lowering the blood glucose levels.

Anti-cancer effects of sitagliptin,vildagliptin,and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

Triple-negative breast cancer(TNBC)cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria.On the other hand,dipeptidyl peptidase-IV(DPP-IV)inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis,but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line.We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase(AMPK),which activates the downstream transcription factors PGC-1α,PGC-1β,or FOXO1 for mitochondrial biogenesis;above-mentioned incretin-based therapies are also known to activate AMPK.This study evaluated the effects of sitagliptin,vildagliptin,and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis,were examined.Treatment with sitagliptin(100μM),vildagliptin(100μM),and exendin-4(10 nM)for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay,cell migration by scratch,and transwell migration assays,accompanied with marginal reduction in cell numbers along with the apoptotic appearance,the rate of apoptosis,and decreased lactate content in conditioned medium.These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio,increased MitoTracker green and red staining,and increased expression of transcription factors PGC-1α,NRF-1,NRF-2,TFAM,and HO-1.Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1μM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay.Thus,sitagliptin,vildagliptin,and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect.Therapeutic response was in the order of:sitagliptin>vildagliptin>exendin-4.

Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide

A linear 7-step synthesis of vildagliptin-β-O-glucuronide (2) starting from commercially available D-glucurono-6, 3-lactone (3) was herein achieved with 11.3% overall yield. Efficient preparation of compound 6 in pure α form was obtained, which was proved critical to achieve high anomeric selectivity in β-O-glycosylation later. The direct β-O-glycosylation of vildagliptin (1) containing both a tertiary alcohol and a secondary amine was studied and achieved in good yield. The deprotection step to afford product was delicately executed to avoid hydrolysis of nitrile group. The target compound 2 was obtained after purification by reversed-phase C18 chromatography.

Validated Chiral Ultra Fast Liquid Chromatographic Method for Quantitative Analysis of Enantiomeric Vildagliptin

A rapid, accurate, and precise chiral Ultra fast liquid chromatography (UFLC) method was developed and validated for enantiomeric separation of racemic vildagliptin and S-vildagliptin according to the guidelines of the International Conference on Harmonization (ICH). The chiral chromatographic separation was achieved with a mobile phase consisting of 20 mM borax buffer (pH 9.0 ± 0.05), ACN, and 0.1% Triethylamine (50:50:0.1, v/v/v) at a flow rate of 1 ml/min using a chiralcel OD-RH column, tris(3,5-dimethyl phenyl carbamate) (250 mm × 4.6 mm, 5 μm) column. The UFLC analysis was monitored at 210 nm. The method showed good linearity with a regression coefficient (r2) of 0.999 in the range of 1 - 12 μg/ml for S-vilda. The detection limit (LOD), quantitation limit (LOQ), and the average percentage recovery for S-vilda were found to be 0.024, 0.075 μg/mL, and 99.19% to 100.4%, respectively. The percentages of relative standard deviation (% RSD) for intra- and inter-day precision were found to be 0.346% and 0.364%, respectively. The developed method proved to be reproducible as % RSD was <2% and it had robustness within the acceptable limit. The percentage purity of pharmaceutical preparations of S-vilda was found to be 99.19 w/w. The proposed chiral method can be put in application for the enantiomeric purity determination of S-vilda formulations.

维格列汀原料药有关物质的合成

为更好地控制维格列汀原料药的质量,改进维格列汀杂质对照品合成方法,结合原料药生产工艺,合成了2个维格列汀原料药的工艺杂质。根据维格列汀原料药降解途径,合成了3个降解杂质。杂质合成无需柱层析,只需要通过简单的重结晶即可得到目标化合物。以核磁共振氢谱、碳谱和高分辨质谱对5个杂质进行了结构确证,通过高效液相测定,这5个杂质的纯度均高于95%,符合杂质定位和含量标定的要求,可以作为原料药检验用的杂质对照品。

维格列汀联合二甲双胍治疗肥胖2型糖尿病患者的效果

目的:观察维格列汀联合二甲双胍治疗肥胖2型糖尿病患者的效果。方法:选取2021年1月至2023年1月该院收治的102例肥胖2型糖尿病患者进行前瞻性研究,按随机数字表法将其分为观察组和对照组各51例。对照组采用二甲双胍治疗,观察组在对照组基础上联合维格列汀治疗,比较两组治疗前后糖代谢指标[空腹血糖(FBG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)]水平、脂代谢指标[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)]水平,脂联素和趋化素水平,临床疗效,以及治疗期间不良反应发生率。结果:治疗后,观察组FBG、2hPG、HbA1c、TC、TG、LDL-C水平均低于对照组,HDL-C水平高于对照组,差异有统计学意义(P<0.05);观察组脂联素水平高于对照组,趋化素水平低于对照组,差异均有统计学意义(P<0.05);观察组治疗总有效率为96.08%(49/51),高于对照组的74.51%(38/51),差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:维格列汀联合二甲双胍治疗肥胖2型糖尿病患者可提高治疗总有效率和脂联素水平,改善脂代谢指标水平,降低糖代谢指标和趋化素水平,效果优于单纯二甲双胍治疗。

达格列净联合维格列汀治疗老年糖尿病肾病患者的效果

目的探讨达格列净联合维格列汀治疗老年糖尿病肾病(DN)患者的效果及对尿蛋白与肌酐比值(uPCR)、肾小球滤过率(eGFR)和血清内皮素-1(ET-1)水平的影响。方法选取98例老年DN患者,随机分为对照组和观察组,各49例,对照组接受维格列汀治疗,观察组接受达格列净联合维格列汀治疗,观察两组治疗前及治疗12周的血糖[空腹血糖(FBG)、餐后2 h血糖(2 h PG)及糖化血红蛋白(HbA1c)]、胰岛素抵抗指数(HOMA-IR)、肾功能(uPCR、eGFR)、血清血管内皮功能指标[血管内皮生长因子(VEGF)、血管生成素1(Ang1)、ET-1]及其他血清生化指标[转化生长因子β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)、组织金属蛋白酶抑制剂-1(TIMP-1)]水平变化。结果治疗12周后,两组FBG、2 h PG、HbA1c、HOMA-IR、uPCR水平低于治疗前(P<0.05),eGFR水平高于治疗前(P<0.05),两组血清VEGF、Ang1、ET-l、TGF-β1及TIMP-1水平低于治疗前(P<0.05),血清MMP-9水平高于治疗前(P<0.05),以上指标观察组的变化幅度大于对照组(P<0.05)。结论达格列净联合维格列汀能有效控制老年DN患者的血糖水平,改善胰岛β细胞功能和肾功能,抑制血清ET-1等血管内皮功能指标和TGF-β1、TIMP-1水平,并可上调MMP-9水平。

维格列汀联合达格列净治疗初诊2型糖尿病患者的效果

目的:观察维格列汀联合达格列净治疗初诊2型糖尿病(T2DM)患者的效果。方法:选取2020年3月至2023年4月该院收治的62例初诊T2DM患者进行前瞻性研究,按照随机数字表法将其分为研究组和对照组各31例。两组均予以饮食和运动指导,在此基础上,对照组口服达格列净治疗,研究组在对照组基础上联合维格列汀治疗,两组均治疗2个月。比较两组临床疗效,治疗前后糖脂代谢指标[空腹血糖(FBG)、餐后2 h血糖(2hPG)、总胆固醇(TC)]水平、胰岛功能指标[空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)]水平、血清学指标[脂联素(APN)、胰高血糖素样肽-1(GLP-1)]水平,以及不良反应发生率。结果:研究组治疗总有效率为93.55%(29/31),高于对照组的74.19%(23/31),差异有统计学意义(P<0.05);治疗后,研究组FBG、2hPG、TC、FINS、HOMA-IR水平均低于对照组,差异有统计学意义(P<0.05);治疗后,研究组GLP-1、APN水平均高于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:维格列汀联合达格列净治疗初诊T2DM患者可提高治疗总有效率和血清学指标水平,降低糖脂代谢指标和胰岛功能指标水平,效果优于单纯达格列净治疗。

维格列汀与二甲双胍治疗新诊断2型糖尿病的临床观察

目的探讨维格列汀联合二甲双胍治疗新诊断2型糖尿病的疗效。方法将79例新诊断2型糖尿病患者随机分为3组,维格列汀组、二甲双胍组,二甲双胍+维格列汀组。治疗12 w后,比较3组治疗前后空腹血糖(FBG)、餐后2 h血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)等指标的变化。结果治疗12 w后,3组FBG、2hPG、HbA1c、HOMA-IR显著下降(P<0.05),FINS显著升高(P<0.05),二甲双胍+维格列汀组比其他两组FBG、2hPG、HbA1c下降更为明显(P<0.05),FINS明显增加(P<0.05)。结论对于新诊断2型糖尿病,维格列汀联合二甲双胍控制血糖效果更为明显。

维格列汀联合门冬胰岛素治疗老年2型糖尿病患者的疗效及安全性

目的观察维格列汀联合门冬胰岛素治疗老年2型糖尿病患者的疗效及安全性。方法对66例使用门冬胰岛素血糖控制不佳的老年2型糖尿病患者随机分两组:观察组36例,加用维格列汀50 mg,2次/d口服;对照组30例,加用阿卡波糖50 mg,3次/d餐中嚼碎服。使用12周后观察两组空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)、空腹C肽、餐后2 hC肽(2 hC肽)、体质量指数(BMI)、肾小球滤过率(GFR)的变化。结果观察组治疗后FBG、2 hPG、HbA1c均较治疗前下降(P<0.05),空腹及2 hC肽较治疗前升高(P<0.05),BMI、GFR与治疗前无明显变化(P>0.05);对照组治疗后2 hPG、HbA1c较治疗前下降(P<0.05),FBG、空腹C肽、2 hC肽、BMI、GFR与治疗前比无明显变化(P>0.05);观察组与对照组相比,FBG显著降低(P<0.05),空腹C肽、2 hC肽显著升高(P<0.05),2 hPG、HbA1c、BMI、GFR无明显差异(P>0.05)。低血糖:两组均无一次发生。结论维格列汀联合门冬胰岛素与阿卡波糖联合门冬胰岛素对降低2 hPG、HbA1c疗效相当,且无体重增加及GFR下降,无低血糖发生。而且维格列汀联合胰岛素较对照组在降低FBG、改善胰岛β细胞功能上作用更明显。

抗糖尿病药物维达列汀

维达列汀是一种口服有效的特异性二肽基肽酶Ⅳ(DPP-Ⅳ)抑制剂,能增强胰高血糖样肽I(GLP-1)活性和降低2型糖尿病患者的高血糖症状。研究表明,维达列汀无论是单用还是与其他抗糖尿病药物合用,均能明显降低具有临床意义的糖基化血红蛋白(HbA1c)水平,具有良好的耐受性,且无体重增加和浮肿等不良反应,低血糖和胃肠道等不良反应发生率也较低。现对其药理作用、药动学、临床研究和不良反应等进行综述。

维格列汀对新诊断2型糖尿病的疗效及对血糖波动的影响研究

目的探讨维格列汀治疗新诊断2型糖尿病的疗效及对血糖波动的影响。方法选择2012年3月—2013年8月在北京军区总医院住院的新诊断2型糖尿病患者68例,采用随机数字表法将患者分为两组:二甲双胍组35例,维格列汀组33例。所有患者均给予常规的饮食及运动治疗,在此基础上,二甲双胍组给予二甲双胍0.5 g,3次/d;维格列汀组给予维格列汀50 mg,2次/d,共治疗12周。比较两组治疗前后的空腹血糖(FPG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)水平,治疗后的血糖标准差(SDBG)、日内平均血糖波动幅度(MAGE)、血糖波动最大幅度(LAGE)、平均餐后血糖波动幅度(MPPGE),并比较不良反应发生率。结果两组治疗前FPG、2 hPG、HbA1c各项指标间差异均无统计学意义(P>0.05);治疗后以上各项指标间差异亦均无统计学意义(P>0.05);治疗后,两组FPG、2 hPG、HbA1c与本组治疗前比较,差异均有统计学意义(P<0.05)。两组治疗后MAGE、LAGE、SDBG、MPPGE各项指标间差异均无统计学意义(P>0.05)。二甲双胍组不良反应发生率为25.7%(9/35),维格列汀组不良反应发生率为6.1%(2/33),两组比较差异有统计学意义(P=0.018)。结论对于新诊断2型糖尿病,维格列汀与二甲双胍控制血糖效果相当,但应用维格列汀患者不良反应更少。

抗糖尿病新药维格列汀

维格列汀(vildagliptin)是继西他列汀(sitagliptin)后的又一个二肽基肽酶-IV(DPP-IV)抑制剂,用于治疗2-型糖尿病。临床研究表明,维格列汀是一个口服有效、市场前景良好的药物,单用或与二甲双胍、胰岛素合用都有明显的降血糖作用,且服用安全,耐受性好,不良反应少。现对其作用机制、药效学、药动学、临床疗效进行综述。

维格列汀联合二甲双胍对2型糖尿病血清氧化物质水平的影响

目的观察维格列汀联合二甲双胍对2型糖尿病患者体内氧化相关物质水平的影响。方法选取2013年3月至2014年3月于辽宁省沈阳市第四人民医院内分泌科住院的二甲双胍单药控制不佳的2型糖尿病患者100例,分为对照组(50例)和观察组(50例)。对照组使用二甲双胍治疗,观察组为二甲双胍与维格列汀联合治疗,连续治疗24周后,比较两组患者治疗前后血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、活性氧类物质(ROS)及空腹血糖(FBG)水平,并比较两组不良反应发生情况。结果治疗24周后,对照组患者外周血清GSH-PX、SOD水平低于观察组,差异有统计学意义(P<0.05);对照组患者外周血清ROS、MDA、FBG水平高于观察组,差异有统计学意义(P<0.05);两组不良反应率比较,差异无统计学意义(P>0.05)。结论在二甲双胍基础上给予维格列汀能通过升高外周血GSH-PX、SOD水平与降低ROS、MDA水平来减轻2型糖尿病患者氧化应激损伤,且不良反应较少。