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.

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.

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。

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。

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。

LC-MS/MS法测定人血浆中维格列汀浓度及其在药动学研究中的应用

目的建立测定人血浆中维格列汀质量浓度的液相色谱-串联质谱(liquid chromatography tandem mass spectrometry,LC-MS/MS)联用方法,考察空腹条件下维格列汀片的人体药动学特征。方法血浆样品经蛋白沉淀法处理,采用稳定同位素标记^(13)C_(5)-^(15)N-维格列汀作为内标,采用Hypurity C_(18)(150 mm×2.1 mm,5μm)色谱柱分离,进行梯度洗脱,流动相为5 mmol·L^(-1)甲酸铵水溶液(A)-乙腈(B),流速为0.5 mL·min^(-1)。在正离子条件下选择多反应离子监测模式进行定量分析。将8名健康受试者采用随机双周期双交叉方式进行空腹试验,并通过WinNonlin 8.1软件计算药动学参数。结果人血浆中维格列汀在质量浓度1.11~534.00μg·L^(-1)内线性关系良好。批内和批间准确度偏差均在±15%以内,精密度相对标准偏差均小于15%。各基质内标归一化的基质因子相对标准偏差均小于5%,选择性、提取回收率、残留效应、稀释可靠性和稳定性均符合要求。结论所建立的方法符合生物样本分析要求,可用于人血浆中维格列汀质量浓度检测及其药动学研究。

二甲双胍/维格列汀和利拉鲁肽对肥胖合并2型糖尿病患者的临床疗效比较

目的评价基于二甲双胍/维格列汀和利拉鲁肽的两种治疗方案对肥胖合并2型糖尿病患者(BMI>25 kg/m^(2))的临床疗效。方法回顾性分析2019~2022年皖南地区107例肥胖合并2型糖尿病患者,根据所选患者初发肥胖合并2型糖尿病,将患者分为二甲双胍/维格列汀治疗组(n=53)和利拉鲁肽治疗组(n=54),持续治疗3个月。比较两组患者治疗前后的BMI、腹围、空腹血糖、餐后2 h血糖、糖化血红蛋白、空腹C肽、餐后2 hC肽、空腹胰岛素及餐后2 h胰岛素,观察治疗前后各项指标的变化。结果107例皖南地区肥胖合并2型糖尿病患者中,二甲双胍/维格列汀组和利拉鲁肽组患者治疗前后的BMI(P<0.05)、腹围(P<0.05)、空腹血糖(P<0.05)、餐后2 h血糖(P<0.05)以及糖化血红蛋白(P<0.05)均较前下降,空腹C肽及餐后2 hC肽较前恢复(P<0.05)。对比两组治疗结果,血糖下降水平疗效相当,但利拉鲁肽组的腹围减少疗效更优(P<0.01),两组治疗方案对患者的胰岛素水平影响并不显著(P>0.05)。结论二甲双胍/维格列汀和利拉鲁肽作为新型降糖药物,对于肥胖合并2型糖尿病具有很好疗效,可以控制血糖、减轻体质量,但利拉鲁肽对患者体质量的控制效果相对更佳。

二甲双胍维格列汀片治疗2型糖尿病合并非酒精性脂肪肝的临床效果研究

目的 分析二甲双胍维格列汀片治疗2型糖尿病合并非酒精性脂肪肝的临床效果。方法 70例2型糖尿病合并非酒精性脂肪肝患者,根据治疗方法的不同分为对照组及复合制剂组,每组35例。对照组患者采取二甲双胍治疗,复合制剂组采取二甲双胍维格列汀片治疗。比较两组治疗前后血脂、血糖、肝功能指标水平及治疗效果、不良反应发生情况。结果 治疗后,复合制剂组总胆固醇(4.04±0.14)mmol/L、低密度脂蛋白胆固醇(2.74±0.53)mmol/L、甘油三酯(1.32±0.51)mmol/L、空腹血糖(FBG)(7.21±1.81)mmol/L、餐后2 h血糖(2 h PBG)(9.01±2.71)mmol/L低于对照组的(5.07±0.15)、(3.82±0.61)、(1.81±0.41)、(9.21±2.41)、(11.12±5.29)mmol/L,高密度脂蛋白胆固醇(2.16±0.42)mmol/L高于对照组的(1.33±0.37)mmol/L,差异具有统计学意义(P<0.05)。治疗后,复合制剂组凝血酶原活动度(PTA)(45.13±12.16)%高于对照组的(38.15±10.20)%,天门冬氨酸氨基转移酶(AST)(40.13±2.13)U/L、总胆红素(TBIL)(181.67±3.52)μmol/L、谷丙转氨酶(ALT)(31.05±2.21)U/L低于对照组的(78.01±2.13)U/L、(251.21±7.45)μmol/L、(140.35±8.74)U/L,差异具有统计学意义(P<0.05)。复合制剂组治疗总有效率94.29%高于对照组的74.29%,差异具有统计学意义(P<0.05)。两组均未出现不良反应。结论 二甲双胍维格列汀片治疗2型糖尿病合并非酒精性脂肪肝的临床效果确切,可有效调节患者的血脂水平,促进患者血糖改善,并改善患者的肝功能,提高治疗的效果。

达格列净和维格列汀对老年糖尿病并冠心病患者VEGF、ET-1、NO的影响

目的评估达格列净、维格列汀应用在老年糖尿病(diabetes mellitus,DM)并冠心病(coronary heart dis‐ease,CHD)患者中的效果及对血管内皮生长因子(vascular endothelial growth factor,VEGF)、内皮素-1(endo‐thelin-1,ET-1)、一氧化氮(nitric oxide,NO)的影响。方法纳入2021年1月—2022年6月平原县中医院收治的102例老年DM并CHD患者,参照随机数表法划分A组(51例,行达格列净治疗)、B组(51例,行维格列汀治疗),评价组间治疗有效率、VEGF、ET-1、NO、左心室射血分数(left ventricular ejection fraction,LVEF)、餐后2 h血糖(2-h postprandial glucose,2 hPG)、空腹血糖(fasting glucose,FPG)、药物不良反应(adverse drug reac‐tions,ADR)等临床指标。结果A组治疗有效率及ADR与B组比较,差异无统计学意义(χ^(2)=0.793、0.000,P>0.05);治疗3个月后,A组VEGF、ET-1、2 hPG、FPG更低,NO、LVEF更高,差异有统计学意义(P<0.05)。结论达格列净、维格列汀在治疗老年DM并CHD患者时疗效、不良反应基本相当,但是前者在改善心功能及血管内皮功能、降低血糖方面更具优势。

维格列汀的空间构型与稳定性的关系

探讨维格列汀的空间结构及其稳定性的关联性。研究采用溶剂挥发法培养得到维格列汀的单晶,运用X射线单晶衍射技术对其立体结构进行解析。该化合物晶态下分子间存在氢键作用,相邻分子间凭借一对氢键形成类二聚体结构,以范德华力和氢键维系其在空间的稳定排列。质量标准中维格列汀的pH为9.7~10.7,因而在碱性和一定湿度下,在辅料微晶纤维素的作用下,破坏分子结构中的氢键,金刚烷上氨基碱性增强,易于进攻吡咯烷上氰基进而环合,这可能是长期放样或加入微晶纤维素,易产生杂质维格列汀环脒的原因。

UPLC-MS/MS法测定维格列汀中4-二甲氨基吡啶

目的建立超高效液相色谱串联质谱法(UPLC-MS/MS)测定维格列汀中基因毒性杂质4-二甲氨基吡啶。方法采用Waters ACQUITY BEH HILIC(50 mm×2.1 mm,1.7μm)色谱柱;流动相为乙酸盐缓冲溶液(10 mmol/L乙酸铵溶液,乙酸调至pH 4.0)-乙腈(体积比10∶90);流速0.3 ml/min,柱温30℃;采用电喷雾离子源(ESI)正离子扫描,以监测模式为多反应监测模式(MRM),定量离子对为123.2→107.1(m/z)进行检测。结果4-二甲氨基吡啶浓度在0.55~10.98 ng/ml范围内与峰面积呈良好线性关系(r=0.9993);定量限为0.02 ng/ml;检出限为0.005 ng/ml;平均加样回收率为91.06%,RSD为1.25%(n=9)。结论本方法专属性强、灵敏度高、准确度好,可用于维格列汀原料药中4-二甲氨基吡啶的测定。