Vildagliptin Therapy Research Articles

Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Antidiabetes Agents in Different Baseline HbA1c Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aim: China PDS aimed to investigate the real-world effectiveness and tolerability of vildagliptin plus metformin (VM) in patients with type 2 diabetes mellitus (T2DM), compared with other oral dual agents (OD). Here, we present the results of prespecified baseline HbA1c subgroups. Materials and Methods: In China PDS, T2DM patients with poor glycemic control by monotherapy were assigned to either VM dual therapy or OD therapy according to local physician’s decision. In this subgroup study, patients were divided into three groups according to their baseline HbA1c levels (≤8%, 8-9%, >9%). The primary outcome was the proportion of patients with HbA1c<7% and without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included mean changes in HbA1c from baseline to study endpoint and tolerability. Results: In total, 7(312 in VM vs. 394 in OD) patients in HbA1c≤8% group, 332 (151 in VM vs. 181 in OD) patients in HbA1c 8-9% group, and 236 (141 in VM vs. 95 in OD) patients in HbA1c>9% group were enrolled. Compared with OD, significantly higher proportion of patients reached primary outcome with VM in HbA1c ≤8% group (57.4% vs. 38.3%, P<0.001), in HbA1c 8-9% group (39.7% vs. 26.0%, P=0.008), and in HbA1c>9% group (48.2% vs. 31.6%, P=0.011). The mean HbA1c changes from baseline to study endpoint in VM and OD were -0.61±0.932 and -0.32±0.874 (P<0.001) in HbA1c≤8% group, -1.37±1.072 and -0.97±1.169 (P<0.001) in HbA1c 8-9% group, and -2.71±1.392 and -2.39±1.4(P=0.305) in HbA1c>9% group. Compared with OD, VM resulted in less tolerability findings (HbA1c≤8%: 7.7% vs. 16.8%; HbA1c 8-9%: 2.6% vs. 9.4%; HbA1c>9%: 5.0% vs. 16.8%; P<0.for all). Conclusion: In different baseline HbA1c groups, vildagliptin plus metformin dual therapy was associated with better glycemic control and good tolerability. Disclosure D. Hu: None. Y. Han: None. L. Chen: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.

Effectiveness and Tolerability of Vildagliptin plus Metformin Dual Therapy Compared with Insulin Secretagogue plus Metformin Dual Therapy in Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aim: The China PDS aims to investigate the effectiveness and safety of vildagliptin dual therapy in type 2 diabetes mellitus (T2DM) patients. Here, we compared the vildagliptin plus metformin (VM) and insulin secretagogue plus metformin (ISM). Materials and Methods: China PDS was a prospective, 1-year, real-world study conducted in 52 sites in patients with T2DM and inadequately controlled on monotherapy. Eligible patients were assigned either vildagliptin dual therapy or other dual therapy according to local physician’s decision. The proportions of patients with HbA1c<7%, without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event), and tolerability were compared in VM and ISM in this study. Results: In total, 933 patients received vildagliptin dual therapy with 64.7% for VM, while 670 patients received other dual therapy with 48.7% for ISM (Table 1). Compared with ISM (31.6%), VM (50.8%) had higher proportion of patients reaching the primary outcome (P<0.001; adjusted OR, 2.14; 95% CI, 1.59-2.87). VM (5.8%) had less tolerability events than ISM (16.4%) (RR, 0.386; 95% CI, 0.26-0.58). Conclusion: China PDS demonstrates that in a real-life setting, VM was effective in glycemic control and was well tolerated when compared with ISM. Disclosure L. Chen: None. Y. Han: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.

Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Agents in Different Regional Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aim: China PDS aims to investigate the real-world effectiveness and tolerability of vildagliptin plus metformin (VM) in patients with type 2 diabetes mellitus (T2DM), compared with other oral dual agents (OD). In this study, we present the results of different regional subgroup analysis. Materials and Methods: In China PDS, T2DM patients with inadequate glycemic control on monotherapy were assigned to either VM dual therapy or OD therapy according to local physician’s decision. In this prespecified subgroup study, patients were divided into three groups according to their geographic regions (East China, North China, and South China). The primary outcome was the proportion of patients with HbA1c<7% and without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included the HbA1c change from baseline to study endpoint, and tolerability. Results: In total, 357 (126 in VM vs. 231 in OD) patients in East China, 499 (292 in VM vs. 207 in OD) patients in North China, and 65 (27 in VM vs. 38 in OD) patients in South Chinawere enrolled. Compared with OD, significantly higher proportion of VM treated patients achieved primary outcome in East China (49.2% vs. 28.1%, P <0.001), North China (52.1% vs. 39.1%, P=0.004), and in South China (66.7% vs. 36.8%, P=0.018). Mean HbA1c changes were significantly greater in VM than in OD in East China (-1.24% vs. -0.55%, P<0.001) and North China groups (-1.35% vs. -0.93%, P=0.011), but not in South China group (-2.12% vs. -1.31%, P=0.147). VM resulted in less tolerability findings than OD in East China (6.3% vs. 18.2) and North China (6.5% vs. 15.0%) groups (P<0.for both), but not in South China group (3.7% vs. 26.3%, P>0.05). Conclusion: In all regional subgroups, vildagliptin plus metformin dual therapy was generally associated with good glycemic control and was well tolerated. Disclosure L. Zang: None. Y. Han: None. L. Chen: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. M. Liu: None. J. He: None. Y. Mu: None.

Glucose excursions and hypoglycemia in patients with type 2 diabetes treated with mitiglinide/voglibose versus glimepiride: A randomized cross-over trial.

Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy. This cross-over trial included 20 patients with type 2 diabetes. After initiating vildagliptin 100 mg, patients were randomly assigned to receive mitiglinide 10 mg/voglibose 0.2 mg three times daily for 3 days followed by glimepiride 1 mg once daily for the subsequent 3 days as add-on therapy, or vice versa. Glucose excursions and hypoglycemia frequency were measured using 24-h continuous glucose monitoring. Metabolic profile changes were evaluated using a meal tolerance test. The mean glucose levels in the mitiglinide/voglibose and glimepiride phases were identical (8.01 vs 8.24 mmol/L, respectively). However, during the mitiglinide/voglibose phase compared with the glimepiride phase, the standard deviation of glucose (1.30 vs 2.10 mmol/L; P < 0.001), mean amplitude of glycemic excursions (3.47 vs 5.28 mmol/L; P < 0.001), M-value (24.6 vs 70.0; P < 0.001), continuous overlapping net glycemic action for a 1-h time interval (22.6 vs 31.0; P < 0.001), and area under the curve >10 mmol/L (0.18 vs 0.52 mmol/L per h; P < 0.001) were significantly lower. Hypoglycemia (glucose <3.8 mmol/L) was not observed during the mitiglinide/voglibose phase, but occurred 0.35 times/day in those taking glimepiride. Moreover, the mitiglinide/voglibose phase had higher premeal and lower post-meal glucose levels than the glimepiride phase. Adding mitiglinide/voglibose to vildagliptin therapy results in more efficient postprandial glucose control and less hypoglycemia than adding glimepiride.

PROSPECTS OF NEPHROPROTECTION AGAINST TYPE 2 DIABETES USING THE DPP-4 INHIBITOR VILDAGLIPTIN

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM), which increases morbidity and mortality. Accumulated evidence, mostly experimental ones that DPP-4 inhibitors have non-glycemic tissue effects including renal protection. Clinical data confirming these effects are insufficient. This makes it relevant to study the influence of iDPP-4 on the renal function in patients with Type 2 diabetes.To study the effects of iDPP vildagliptin on glycemic, metabolic and renal parameters in patients with type 2 diabetes with CKD 1–2 receiving insulin therapy 44 patients were randomized to continue therapy with insulin or insulin + vildagliptin at a dose of 50 mg/day, with the evaluation of results in 6 months.In group of vildagliptin therapy a significant decrease of HbA1c, postprandial glycemia, diastolic blood pressure, HOMA-IR, insulin demand and a reduction in the frequency of hypoglycemia occurred. The positive dynamics of indicators of glomerular functions of the kidney were noted in this group - a significant reduction in albuminuria and a significant increase in eGFR by cystatin C and decreased urinary excretion of type IV collagen. The findings suggest the positive effect of vildagliptin on metabolic status and indicators of glycaemia and hemodynamics as earlier confirmed in clinical studies and the ability of vildagliptin independent from glycemic effects to slow the development of glomerular dysfunction in patients with type 2 diabetes and the initial manifestations of DN.

Dipeptidyl peptidase-4 inhibitor enhances restoration of salivary glands impaired by obese-insulin resistance

ObjectiveChronic high-fat diet consumption causes not only obese- insulin resistance, but also leads to pathological changes in salivary glands, including increased mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. Dipeptidyl peptidase-4 inhibitor (vildagliptin) is an oral anti-diabetic drug, using for treatment of type 2 diabetes. Vildagliptin has been shown to exert beneficial effects on several organs in cases of obese-insulin resistant condition. However, the effect of vildagliptin on salivary glands impaired by obese-insulin resistance has not been investigated. The hypothesis in this study is that vildagliptin confers beneficial effects on the salivary gland impaired by obese-insulin resistance via decreasing mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. DesignTwenty-four male Wistar rats were divided into two groups. Each group was fed with either a normal (ND; n=8) or a high fat diet (HFD; n=16) for 16 weeks. At week 13, the HFD-fed rats were subdivided into 2 subgroups to receive either a vehicle or vildagliptin (3mg/kg/day) for 28days via gavage feeding. ND-fed rats were treated with the vehicle. At the end of treatment, metabolic parameters were examined, and rats were killed. Submandibular glands were removed to appraise inflammatory markers, apoptosis and mitochondrial function. ResultsVehicle-treated HFD-fed rats developed obese-insulin resistance with an increase in oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction in the salivary glands. Vildagliptin therapy reduced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction in salivary gland of HFD-fed rats. ConclusionVildagliptin prevented salivary gland injury occurring due to obese-insulin resistance.

The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin.MethodsIn this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500–750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed.ResultsNinety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m2; HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (− 0.80 ± 0.38% vs. − 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (− 0.51 [− 1.08–0.06]% vs. − 0.58 [− 1.20–0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66–0.62; p < 0.01), the change did not differ significantly between the two groups (− 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 μg/mL vs. 0.01 μg/mL; p < 0.01).ConclusionsRegardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis.

THEEFFECT OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS ON CARDIOVASCULAR DISEASE RISK IN TYPE 2 DIABETES MELLITUS

&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this study was is to investigate the proposed beneficial cardiovascular effects of a novel class of antidiabetic drugs named; dipeptidyl peptidase 4 inhibitors. In this study, we compared the effect of using add-on therapy of vildagliptin (dipeptidyl peptidase-4 inhibitor; DPP-4i) and gliclazide (sulphonylurea; SU) to that when using gliclazide monotherapy in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS) on different cardiovascular outcomes.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 60 patients diagnosed with T2DM, and ACS were randomly recruited into two treatment groups each of 30 patients to receive either gliclazide monotherapy (SU) or vildagliptin (DPP4i)+gliclazide (SU) add-on therapy, administered in a double-blind fashion. Outpatient visits were scheduled at 3, 6, and 12 mo where patient was reevaluated for cardiovascular (CV) outcomes and followed up for any arising cardiovascular complication.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The vildagliptin (DPP4i) plus gliclazide (SU) add-on therapy group have significantly shown more improved glycemic control, lipid profile and ventricular performance compared to gliclazide (SU) monotherapy group with p values&amp;lt;0.05.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p dir="LTR"&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Vildagliptin as a DPP4i provides favourable cardiovascular effects beyond glucose control. Yet, its long-term safety and efficacy data still needs further investigations.&lt;/p&gt;

INFLUENCE OF VILDAGLIPTIN AND GLIQUIDONE COMBINATION ON P-GLYCOPROTEIN FUNCTIONAL ACTIVITY AND EXPRESSION ON THE BACKGROUND OF NORM AND IN EXPERIMENTAL ALLOXAN-INDUCED DIABETES MELLITUS TYPE 2

In the in vivo study on rabbits investigated the effect of the vildagliptin and gliqui-done combination on the background of norm and experimental alloxan-induced diabetes mellitus (DM) type 2 on the P-glycoprotein (P-gp, ABCB1 protein) functional activity and its expression in the tissues of the jejunum, liver, kidney and the blood-brain barrier. Introduction of combination of vildagliptin at a dose of 5 mg/kg and gliquidone 10 mg/kg body weight on the background of norm for 14 days did not result in P-glycoprotein changes. On the 5-day of the cancellation of this combination observed inhibition of transporter protein functional activity without altering its expression. In the combination therapy of vildagliptin and gliquidone alloxan-induced diabetes type 2 showed complete recovery of P-glycoprotein functional activity and expression reduced on the pathology background. On the 5-day of treatment withdrawal again occurred inhibition of functional activity of the transporter protein and a decrease in its expression.

Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment.

The use of dipeptidyl peptidase (DPP)-4 inhibitors in patients with type 2 diabetes treated with insulin may be beneficial. However, the long-term efficacy and safety of vildagliptin add-on therapy in these patients remains unclear. A total of 73 patients with type 2 diabetes treated with insulin were randomly assigned to receive either add-on therapy of vildagliptin (n=37) or conventional therapy without DPP-4 inhibitors (n=36) for glucose control. Hemoglobin A1c (HbA1c) levels, dose and number of insulin injections, number of hypoglycemia episodes, and liver and renal function were monitored for 2years. The baseline characteristics of subjects, including age, dose of insulin injections, or HbA1c levels, did not differ between the two groups. In the vildagliptin group, HbA1c levels significantly decreased and the significance of HbA1c reduction was maintained for 24months (from 8.0±1.2% to 7.4±1.0%, p<0.05, at the end of observational period). In addition, the dose and number of insulin injections significantly reduced (-5.6units, p<0.01, and -0.9 times, p<0.001). However, these parameters were unchanged in the control group. The number of patients who experienced three or more episodes of hypoglycemia per year was significantly lower in the vildagliptin group (n=4) than in the control group (n=11) (odds ratio, 0.28; 95% confidence interval, 0.08-0.97; p<0.05). Vildagliptin as an add-on to insulin treatment for 24months was well tolerated and led to sustained reductions in HbA1c, the dose and number of insulin injections, and the risk of hypoglycemia.

Long-term efficacy and safety of add-on therapy of vildagliptin in type 2 diabetes mellitus with insulin treatment

Long-term efficacy and safety of add-on therapy of vildagliptin in type 2 diabetes mellitus with insulin treatment

Adverse Effects of Combinatorial Therapy of Vildagliptin and Insulin on Cardiac Tissues in Diabetic Rats

Objectives: This study is aimed to evaluate the cardiovascular adverse effects of fixed dose combination of vildagliptin (10 mg/kg body weight) and insulin (0.27 I.U/kg body weight) on alloxan induced diabetic rats. Methods and Analysis: The cardiac tissues were weighed and homogenized using ice cold phosphate buffer, centrifuged and the supernatant used for further parameters. The different parameters were measured spectrophotometrically and statistical analysis of data was done by ANOVA followed by dunnet's post hoc test. The test samples consist of diabetic animal fed with vildagliptin and insulin as monotherapies and also as combinatorial therapy and the approach used for comparing them is by SPSS data analysis software version 19.0. Findings: The histopathological studies show that in combinatorial therapy of vildagliptin and insulin in alloxan an induced diabetic rat shows pathological lesions, inflammatory infiltration and eosinophylic cytoplasm. With regard to cardiac marker enzymes their levels were significantly elevated in combinatorial therapy showing cardiac damage. With regard to lipid profile the total cholesterol has been significantly reduced in combinatorial therapy showing it was not properly metabolized. These results were analysed by dunnet's post hoc test and the level of significance was set at p<0.05. The drugs are producing severe adverse effects only at the post clinical trial stage. Our studies focus on the adverse effects produced by the drugs at the post clinical trial stage. Monitoring adverse drug reaction is still at a nascent stage owing to lack of awareness and healthcare professionals abstaining from reporting negative effects of pharmaceuticals. So our studies will be really helpful for developing new drugs which are devoid of adverse effects. Applications and Improvement: Our research will be a great resource for the pharmaceutical sector to develop new drugs which are devoid of all these adverse effects.

Development of Transdermal Delivery System of Vildagliptin and Its Comparison with Oral Therapy.

Purpose: The long term oral therapy of vildagliptin is associated with potential hepatotoxicity and low patient compliance. This study aims at development of a drug in adhesive transdermal patch system of vildagliptin using pressure sensitive acrylic polymers and compare the pharmacokinetics with oral therapy. Methods: The prospective of different chemical enhancers in improving the transport of vildagliptin was assessed ex vivo. In vivo permeation studies in rats were performed using patch system contain sodium lauryl sulfate as enhancer. Results: Drug solubility varied among adhesive bases tested and maximum value (15% w/w) observed with Duro-Tak 87-2510. Incorporation of chemical agents significantly improved the permeation of vildagliptin, but not to the same extent. The highest flux value of vildagliptin was obtained by the addition of sodium lauryl sulfate (22.96 ± 3.58 μg/cm2/h; P<0.0001), which is ~4 folds higher as compared to control. Pharmacokinetic profiles of vildagliptin were different for transdermal and oral delivery with significantly high bioavailability by transdermal delivery. The AUC0-α in transdermal delivery (1018.43 ± 79.56 ng.h/mL) was ~14 folds higher (P<0.0001) as compared to oral administration. Conclusion: The current study concludes that the fabricated drug in adhesive transdermal system could be employed for the effective delivery of vildagliptin.

Long-term efficacy of vildagliptin in patients with type 2 diabetes undergoing hemodialysis.

BackgroundThere are few studies evaluating long-term glycemic control using a dipeptidyl peptidase-4 inhibitor in type 2 diabetes patients with end-stage renal disease (ESRD). The aim of this study was to evaluate the safety and efficacy of vildagliptin therapy over 2 years in type 2 diabetes with ESRD.MethodsPatients with ESRD resulting from type 2 diabetes requiring dialysis who had ≥20 % glycated albumin (GA) were enrolled. Vildagliptin 50 mg once daily was administered for 2 years. Changes in GA and dry weight were evaluated.ResultsIn 32 patients (24 men and 8 women) aged 68.3 ± 1.9 years, vildagliptin 50 mg once daily was administered for 2 years, but the dose was increased to 50 mg twice daily in 15 patients. GA was significantly reduced by 2.6 ± 0.6 %, from 22.4 ± 0.6 % at baseline to 19.8 ± 0.4 % at 2 years. After 2 years of vildagliptin therapy, 15 (46.9 %) of 32 patients achieved a GA level of <20 %. Dry weight changed slightly, with an increase of 1.3 ± 0.8 kg at 2 years. No adverse drug reactions related to treatment with vildagliptin were seen.ConclusionsVildagliptin is a promising therapeutic option for safe, effective glycemic control in type 2 diabetic patients with ESRD.

Effect of Acarbose on Glycemic Variability in Patients with Poorly Controlled Type 2 Diabetes Mellitus Receiving Stable Background Therapy: A Placebo-Controlled Trial.

To evaluate the effect of acarbose on glycemic control and glycemic variability, using a continuous glucose-monitoring system, in patients with type 2 diabetes mellitus who were not well controlled on metformin and vildagliptin therapy. Multicenter, randomized, double-blind, placebo-controlled study. Clinical research units at three hospitals in Italy. Fifty-three patients with type 2 diabetes who were taking stable dosages of metformin 850 mg 3 times/day and vildagliptin 50 mg twice/day for at least 3 months and who were not adequately controlled with these therapies. Patients were randomized to either placebo or acarbose 100 mg 3 times/day to be added to their metformin-vildagliptin regimen. Glycemic excursions were assessed by using a continuous glucose-monitoring system for 1 week. Glycemic control was estimated as the mean blood glucose (MBG) level, the area under the glucose concentration-time curve for a glucose level above 70 mg/dl (AUC above 70) or 180 mg/dl (AUC above 180), and the percentage of time that the glucose level was above 70 mg/dl (T above 70) or 180 mg/dl (T above 180). Intraday glycemic variability was assessed by the standard deviation of the blood glucose level, the mean amplitude of glycemic excursions (MAGE), the M value, and continuous overlapping net glycemic action. Day-to-day glycemic variability was assessed as the mean of daily difference (MODD). The MBG level was ~20 mg/dl lower in the acarbose group than in the placebo group (p<0.05), particularly during the postprandial period. The AUC above 70 did not significantly differ between the two groups, whereas the AUC above 180 was ~40% lower in the acarbose group than in the placebo group during the daytime (p<0.01). The T above 180 was significantly higher in the placebo group than in the acarbose group (31% vs 8%, p<0.01. Moreover, the standard deviation and MAGE values were significantly lower in the acarbose group. The MODD value was not significantly changed in either group, and no significant differences were recorded between groups. All adverse events were mild in both groups, with only a significantly greater frequency of flatulence noted in the acarbose group (5% with acarbose vs 0.5% with placebo, p<0.05). The addition of acarbose to metformin and vildagliptin background therapy in patients with inadequately controlled type 2 diabetes decreased intraday glycemic variability, especially postprandial variability, but it was not associated with a significant change in interday glycemic variability.

Beneficial Effects of Vildagliptin on Metabolic Parameters in Patients with Type 2 Diabetes.

Blood pressure and lipid profile are important determinants of cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). To identify the pleiotropic effects of vildagliptin other than blood glucose lowering effect, a retrospective study was conducted in 128 patients with T2DM treated with vildagliptin 50 mg twice daily. The patients were separated into two groups: patients who were initiated with vildagliptin as monotherapy or add-on therapy (add-on group, n = 66) and patients who were switched from sitagliptin 100 mg once daily to vildagliptin (switching group, n = 62). Hemoglobin A1c (HbA1c), body mass index (BMI), systolic/diastolic blood pressure, lipid profiles, and uric acid (UA) at 3, 6, and 12 months of vildagliptin therapy were compared with those at baseline in each group. At baseline, there were no significant differences in HbA1c, BMI, blood pressures, lipid profiles, and UA levels between the two groups. After vildagliptin initiation, HbA1c decreased significantly but BMI and blood pressure did not change in both groups. Only in the add-on group, total cholesterol and low density lipoprotein cholesterol decreased significantly from baseline to 3, 6, and 12 months. On the other hand, triglyceride and high-density lipoprotein cholesterol did not change in both groups. Serum UA levels decreased only in the switching group from baseline to 3, 6, and 12 months. These results indicate that vildagliptin add-on treatment may have beneficial effects on lipid profiles, and switching from sitagliptin to vildagliptin reduces UA in patients with T2DM; these are important findings linked to the beneficial effects of vildagliptin on lipid and UA metabolisms in the treatment of T2DM.

Changes in body weight after 24 weeks of vildagliptin therapy as a function of fasting glucose levels in patients with type 2 diabetes.

BackgroundIn order to test the hypothesis that the degree of weight change with the dipeptidyl peptidase-4 inhibitor vildagliptin is dependent on the level of glycemic control at baseline, the weight changes from pooled monotherapy studies after 24 weeks of therapy with vildagliptin were assessed versus the fasting plasma glucose (FPG) levels at baseline.MethodsData were pooled from eight clinical monotherapy trials including 2,340 previously drug-naïve patients with type 2 diabetes mellitus who received vildagliptin monotherapy (50 mg once daily [n=359] or 50 mg twice daily [n=1,981]). The trials were all randomized, double-blind, controlled clinical trials with a prespecified week 24 study visit.ResultsLinear regression analysis of weight change after 24 weeks relative to baseline FPG showed an intercept of −2.259 kg (95% confidence interval −2.86, −1.66; P<0.0001) and a positive slope of 0.1552 kg (95% confidence interval 0.10–0.21; P<0.0001). Neutral caloric balance (no weight change) was observed at a FPG of 14.6 mmol/L (263 mg/dL). Baseline FPG values below and above this threshold were associated with weight loss and weight gain, respectively. For instance, from this analysis, a baseline FPG of 8 mmol/L (144 mg/dL) predicts a weight loss of 1 kg.ConclusionThe present analysis showed that treatment with vildagliptin results in a negative caloric balance when glucose levels are below the renal threshold at baseline.

Efficacy Of Add - On Vildagliptin Therapy To Metformin For Type Ii Diabetes Mellitus Patients In South Indian Resource Limited Settings - Pilot Study.

Prevalence of diabetes mellitus is increasing globally in most developed and developing countries and Dipeptidyl peptidase-4 inhibitors (Gliptins) are recently introduced class of drugs for type 2 diabetes mellitus which shows good glycemic control. It is a prospective interventional pilot study aimed to determine the efficacy of add-on vildagliptin therapy to metformin in type 2 diabetes mellitus patients for a period of 6 months in south Indian resource limited settings A total of 185 patients were enrolled into the study. The study subjects were assigned into three groups based on their existing treatment (initiated within one month) i.e., group I (vildagliptin and metformin), group II (vildagliptin alone) and group III (metformin alone). They were also assessed for baseline demographic characteristics. Medication adherence was measured to ensure that patients are complies with the treatment. The clinical endpoint was estimated by using various variables like quality of life and other clinical endpoints such as RBS, PPBS after three months of specific treatment through direct interview and by referring the medical case records. The results show that there is no significant difference in individual groups in terms of demographic characteristics. (P >0.01). And all the present study subjects are found to have more than 90 % of medication adherence. We observed high level of significant improvement in group I (93.18±3.76) subjects whereas low level of improvement in group III subjects (90.4±4.13) after the relevant treatment (P = 0.003). Group I subjects are also found to have good glycaemic control (RBS, FBS and PPBS) than any other treatment groups P<0.01). Add on vildagliptin therapy to metformin might improve the quality of life of type 2 diabetes mellitus patients and might be useful to bring the glycemic levels under control in type 2 diabetic patients in South Indian resource limited settings.

Multifactorial effects of vildagliptin added to ongoing metformin therapy in patients with type 2 diabetes mellitus

BackgroundTo assess the efficacy of a vildagliptin and metformin combination therapy to a metformin monotherapy in type 2 diabetes mellitus patients. MethodsSixty-one patients with diabetes inadequately controlled by a metformin monotherapy were randomized to treatment with a combination therapy of vildagliptin 100mg and a metformin versus metformin monotherapy. This was a 12-week randomized parallel group study. During the study we assessed parameters of glycemic and lipid metabolism as well as the treatment effects on the release of proinflammatory and antiinflammatory cytokines. ResultsCompared with baseline values we observed a significant improvement of glycaemic parameters such as HbA1c, FPG, PPG, FPI, HOMA-IR and HOMA-β index as well as decrease of TCh, TG and LDL and an increase of HDL with the greatest extent of vildagliptin plus a low-dose metformin therapy group. A metformin combination therapy significantly decreased such inflamation parameters as hs-CRP, ox-LDL, TNF-α and IL-1β levels relative to monotherapies. All treatments were well tolerated and there was no incidence of hypoglycaemia. ConclusionsVildagliptin added to an ongoing metformin therapy allows to achieve better metabolic control parameters in comparison with a metformin monotherapy and the combination treatment is well tolerated and has a low risk of serious adverse effects.

Randomized controlled clinical trial of a combination therapy of vildagliptin plus an α-glucosidase inhibitor for patients with type II diabetes mellitus.

The aim of this study was to assess the efficacy of a combination therapy of vildagliptin plus an α-glucosidase inhibitor for patients with type II diabetes mellitus. Type II diabetic patients exhibiting poor glycemic control following α-glucosidase inhibitor treatment for at least two months were selected and randomly distributed into vildagliptin and placebo groups. The body weight, fasting blood glucose (FBG), postprandial glucose (PPG), glycated hemoglobin (HBA1c) and blood lipid levels and hepatorenal functions of the patients were determined before and 12 weeks after the trial. Following the trial, the FBG, PPG, HbA1c, cholesterol (CHOL) and triglyceride (TG) levels in the vildagliptin group were significantly decreased compared with the pretreatment levels (P<0.05), whereas only the PPG level in the placebo group decreased (P<0.05). The FBG, PPG and HbA1c levels in the vildagliptin group were markedly lower than those in the placebo group 12 weeks after the trial. A comparison of the body weights and hepatorenal functions before and after the trial or between groups did not show statistically significant differences. The combination therapy of vildagliptin plus an α-glucosidase inhibitor effectively reduced the FBG, PPG and HbA1c levels in patients without inducing weight gain or hepatorenal dysfunction. However, the therapy may have caused a reduction in the blood lipid levels.