Tolerability Of Vildagliptin Research Articles

Efficacy and Safety of a Fixed-Dose Combination of Vildagliptin and Pioglitazone in Indian Patients With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Comparative, Phase III Study.

Background Type 2 diabetes mellitus (T2DM) arises due to a range of pathological abnormalities, necessitating a combination therapy to achieve optimal glycemic control. Vildagliptin, an effective and selective DPP-4 inhibitor, and pioglitazone, an insulin sensitizer, offerdistinct mechanisms of action. Hence, the integration of these medications represents a logical and justified therapeutic strategy Objective To compare the efficacy, safety, and tolerability of vildagliptin and pioglitazone 50 mg/15 mgfixed-dose combination (FDC) tablets with individual monotherapy vildagliptin 50 mg and pioglitazone 15 mg tablets in Indian T2DM patients who were inadequately controlled on metformin monotherapy. Methods This was a randomized, open-label, comparative, multicenter, phase III study involving 195 T2DM patients with inadequate glycemic control on metformin ≥ 1000 mg/day. Patients were randomly assigned in a 1:1:1 ratio to the test product group (n=65) (vildagliptin 50 mg + pioglitazone 15 mg FDC tablets), reference product group 1 (n=65) (vildagliptin 50 mg tablet), or reference product group 2 (n=65) (pioglitazone 15 mg tablet reference product). The primary endpoint was the mean change in HbA1c levels from baseline to end of the study visit (12 weeks (84 days ±2)). The secondary endpoints were the mean change in fasting plasma glucose (FPG) and 2-hr postprandial plasma glucose (2-hr PPG) levels. Safety parameters were assessed till the end of the study. Results A total of 178 patients completed the study. At 12 weeks, the mean HbA1c level in the test group reduced to 6.85 ± 1.27%, in the reference product 1 group to 7.56 ± 1.72%, and in the reference product 2 groups to 7.37 ± 1.59%. The mean change in Hb1Ac from baseline in the test group was statistically significant compared to the reference groups (p=0.037). Similarly, the mean changes in the FPG and 2hr-PPG with the test product were statistically significant compared to reference products (p=0.041). The adverse events were comparable across all the treatment groups. Conclusion In Indian T2DM patients inadequately controlled on a daily maximum dose of metformin, treatment with vildagliptin and pioglitazone FDC showed better glycemic control than either vildagliptin or pioglitazone along with a good tolerability profile.

SAFETY AND TOLERABILITY OF VILDAGLIPTIN IN CLINICAL PRACTICE: NEWER PROMISING GLIPTIN FOR TYPE 2 DIABETES MELLITUS

The prevalence of type 2 diabetes (T2DM) increases with age. Older patients have an increased likelihood for T2DM-related morbidity and mortality. The dipeptidyl peptidase-4 inhibitor vildagliptin is approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. This article reviews the clinical efficacy and tolerability of vildagliptin in the treatment of type 2 diabetes, as well as summarizing its pharmacological properties. Improvements in glycaemic control were also seen with vildagliptin in elderly patients with type 2 diabetes and in patients with type 2 diabetes and moderate or severe renal impairment. Vildagliptin was generally well tolerated in patients with type 2 diabetes, was weight neutral and was associated with a low risk of hypoglycemia, reflecting its glucose-dependent mechanism of action. The elderly population with T2DM poses unique treatment challenges and have not been particularly well-represented in clinical trials, highlighting the need for additional studies to better define appropriate glucose targets and to ascertain the best strategies for achieving and maintaining appropriate glycaemic levels. In conclusion, vildagliptin is an important option for use in combination with metformin, a sulfonylurea or a thiazolidinedione in patients with type 2 diabetes who require combination therapy.
 Keywords: DPP-4 inhibitors, Elderly, Oral hypoglycemic agents, Type 2 diabetes, Vildagliptin

Effectiveness, safety, and tolerability of vildagliptin or vildagliptin/metformin combination in patients with type 2 diabetes uncontrolled on insulin therapy in a real-world setting in Egypt: The OMEGA study

PurposeTo evaluate the effectiveness and safety of vildagliptin or vildagliptin/metformin combination among patients with type 2 diabetes mellitus (T2DM) uncontrolled on insulin in a real-world setting in Egypt. MethodsThis 12-week, prospective, observational study enrolled T2DM patients. Primary endpoint was mean change in glycated hemoglobin (HbA1c) from baseline to Week 12. Secondary endpoints included mean change in body weight, insulin dosage and safety after 12 weeks. ResultsOf the 90 patients enrolled, 88 (93.6%) completed the study. The mean age was 54.7 years; men, 51.1%; body mass index (BMI), 31.6 kg/m2; T2DM duration, 89.8 months; insulin dose, 55.14 IU/day. At 12 weeks, HbA1c decreased significantly with vildagliptin/metformin (−1.3 ± 0.9%, p < 0.0001) and vildagliptin (−1.1 ± 0.9%, p = 0.0001). 27.1% and 11.1% achieved HbA1c <7% in vildagliptin/metformin and vildagliptin groups, respectively. Significant mean (±standard deviation [SD]) reduction in body weight (−2.5 ± 7.3 kg, p = 0.0055) and insulin dose (−24.11 ± 22.3 IU, p < 0.0001) was observed in the vildagliptin/metformin group. Overall, 8 (8.9%) patients reported 11 (12.2%) adverse events (AEs) and no hypoglycemic events. AEs possibly related to the study drug (4.2%, in vildagliptin/metformin) were mild in severity. ConclusionVildagliptin with/without metformin as an add-on to insulin resulted in good glycemic control and was well tolerated without any hypoglycemic events.

Vildagliptin Versus α-Glucosidase Inhibitor as Add-On to Metformin for Type 2 Diabetes: Subgroup Analysis of the China Prospective Diabetes Study.

IntroductionThe effect of dipeptidyl peptidase-4 (DDP-4) inhibitors versus α-glucosidase inhibitors (AGIs) on the treatment of type 2 diabetes mellitus (T2DM) in a real-world setting is unknown. The aim of this real-world study was to compare the glucose-lowering effect and tolerability of vildagliptin as add-on to metformin monotherapy (VM) and AGI as add-on to metformin monotherapy (AM) in Chinese patients with T2DM.MethodsThis was a subgroup analysis of the China Prospective Diabetes Study, a post-marketing, prospective, observational, real-world study conducted at 52 centers in China. T2DM patients with inadequate glycemic control on metformin monotherapy who received VM or AM were included. The composite primary endpoint was glycemic control (hemoglobin A1c [HbA1c] < 7%) after 12 months in the absence of tolerability events (hypoglycemia, weight gain ≥ 3%, or gastrointestinal events leading to treatment discontinuation). Propensity score matching (PSM) was used to balance the two groups.ResultsThe success rates of the composite endpoint were higher in the VM group (n = 604/159 before/after PSM) than in the AM group (n = 159/157 before/after PSM), but the difference was not statistically significant (before PSM: 53.0 vs. 46.5%, P = 0.148; after PSM: 56.7 vs. 45.9%, P = 0.055). The glycemic control rate and HbA1c reduction were similar between groups at 3, 6, and 12 months. Compared with the AM group, the VM group had lower risks of any tolerability event (relative risk [RR] 0.53, 95% confidence interval [CI] 0.33–0.83, P = 0.006), of any adverse event (AE) (RR 0.64, 95% CI 0.41–1.00, P = 0.049), and of any serious AE (RR 0.45, 95% CI 0.25–0.81, P = 0.007).ConclusionThe results of this real-world study suggest that vildagliptin as add-on to metformin monotherapy had a similar glucose-lowering effect to AGI as add-on to metformin monotherapy, but with better safety.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-00742-8) contains supplementary material, which is available to authorized users.

Effectiveness and Tolerability of Vildagliptin and the Single Pill Combination of Vildagliptin and Metformin in "Real-World" Management of Type 2 Diabetes Mellitus: The G-FORCE Study.

IntroductionRandomized clinical trials showed that vildagliptin is well tolerated and leads to clinically meaningful decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) both in monotherapy and as add-on therapy in inadequately controlled type 2 diabetes mellitus (T2DM) patients. Nevertheless, there is an increased interest for real-life studies to confirm the clinical trial findings in the setting of a daily clinical practice. The aim of this study was to evaluate the effectiveness and tolerability of vildagliptin in a real-life clinical setting and to explore factors determining drug adherence and T2DM management.MethodsG-FORCE was a prospective, observational, open-label, multi-center study in which T2DM patients were prescribed de novo vildagliptin. Clinical effectiveness was determined by changes in HbA1c and FPG and by the proportion of patients reaching glycemic goal. Data were collected at baseline, after 105 ± 15 days and after 180 ± 15 days.ResultsA total of 1230 patients were included in this analysis. Mean age was 63.9 ± 10.8 years, and mean HbA1c and FPG levels were 8.2 ± 1.3% and 171.0 ± 53.3 mg/dL, respectively. At 180 days of treatment, HbA1c and FPG levels decreased to 7.2 ± 1.0% and 141.1 ± 44.0 mg/dL, respectively, while the proportion of patients reaching HbA1c and FPG goals rose from 8.6 to 44.6% and from 14.2 to 42.8%, respectively.ConclusionIn this real-world study, vildagliptin was an effective and safe treatment for T2DM patients already treated with metformin, while the single pill combination of vildagliptin and metformin provides a convenient alternative while ensuring comparable effectiveness and tolerability.FundingNovartis Pharma.

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%, &amp;gt;9%). The primary outcome was the proportion of patients with HbA1c&amp;lt;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&amp;gt;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&amp;lt;0.001), in HbA1c 8-9% group (39.7% vs. 26.0%, P=0.008), and in HbA1c&amp;gt;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&amp;lt;0.001) in HbA1c≤8% group, -1.37±1.072 and -0.97±1.169 (P&amp;lt;0.001) in HbA1c 8-9% group, and -2.71±1.392 and -2.39±1.4(P=0.305) in HbA1c&amp;gt;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&amp;gt;9%: 5.0% vs. 16.8%; P&amp;lt;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 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&amp;lt;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 &amp;lt;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&amp;lt;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&amp;lt;0.for both), but not in South China group (3.7% vs. 26.3%, P&amp;gt;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.

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

Background and Aim: The real-world study of China PDS with 2083 type 2 diabetes mellitus (T2DM) patients showed that vildagliptin plus metformin (VM) therapy could effectively control the HbA1c with good tolerability. Here, we present the results of baseline BMI subgroups. Materials and Methods: In China PDS, T2DM patients with poor glycemic control on monotherapy were assigned to either VM dual therapy or other oral dual agents(OD) therapy according to local physician’s decision. For this analysis, patients were divided into three subgroups according to baseline BMI(&amp;lt;24kg/m2, 24-28kg/m2, &amp;gt;28kg/m2). The primary outcome was the proportion of patients with HbA1c&amp;lt;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, 389(149 in VM vs. 240 in OD) patients in BMI&amp;lt;24kg/m2 group, 625(304 in VM vs. 321 in OD) patients in BMI 24-28kg/m2 group, and 260(151 in VM vs. 109 in OD) patients in BMI&amp;gt;28kg/m2 group were enrolled. Compared with OD, significantly higher proportion patients reached primary outcome in VM in BMI&amp;lt;24kg/m2 group (47.0% vs. 35.0%; P=0.019), in BMI 24-28kg/m2 group (52.6% vs. 33.3%; P&amp;lt;0.001), and in BMI&amp;gt;28kg/m2 group (51.0% vs. 33.9%; P=0.006). Mean HbA1c changes were significantly greater in VM than in OD(BMI&amp;lt;24kg/m2: -1.23% vs. -0.76%; BMI 24-28kg/m2: -1.32% vs. -0.79%; BMI&amp;gt;28kg/m2: -1.29% vs. -0.84%; P&amp;lt;0.for all). VM resulted in less tolerability findings than OD in BMI&amp;lt;24kg/m2 (11.4% vs. 19.2) and BMI 24-28kg/m2 (3.6% vs. 14.6%) groups (P&amp;lt;0.for both), but not in BMI &amp;gt;28kg/m2 group (4.6% vs. 5.5%, P&amp;gt;0.05). Conclusion: In different baseline BMI groups, vildagliptin plus metformin dual therapy was associated with better glycemic control and was well tolerated compared with OD. Disclosure H. Jin: None. Y. Han: None. L. Chen: None. D. Hu: 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&amp;lt;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&amp;lt;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 Antidiabetes Agents in Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aims: This real-world study aimed to assess the effectiveness and safety of vildagliptin plus metformin (VM) vs. other oral dual antidiabetes agents (OD) in type 2 diabetes mellitus (T2DM) patients in China. Materials and Methods: This prospective, 1-year, real-world study was conducted in 52 sites in patients inadequately controlled by monotherapy. Eligible patients were assigned either vildagliptin dual therapy or other OD according to local physician’s decision. The primary outcome was the proportion of patients with HbA1c&amp;lt;7%, without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included subgroup analysis and tolerability. Results: Totally 604 patients received VM and 670 patients received OD. After propensity score-matched, baseline HbA1c and BMI were similar in both groups. After 12-month treatment, 55.4% patients in VM and 36.2% in OD reached primary outcome (P&amp;lt;0.001; OR, 1.88; 95% CI 1.47-2.40). In all subgroups, VM significantly benefited the primary outcome (Figure 1). Numerically, less tolerability events occurred in VM vs. OD (5.8% vs. 14.8%). Conclusion: China PDS demonstrates that in a real-life setting, vildagliptin plus metformin is effective in glycemic control and is well tolerated. Disclosure Y. Han: None. L. Chen: 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.

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance.

Vildagliptin is one of the most extensively studied dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of its clinical utility. Over the last decade, a vast panorama of evidence on the benefit–risk profile of vildagliptin has been generated in patients with type 2 diabetes mellitus (T2DM). In this article, we review the cumulative evidence on the safety of vildagliptin from the clinical development programme, as well as reports of rare adverse drug reactions detected during the post-marketing surveillance of the drug. Across clinical studies, the overall safety and tolerability profile of vildagliptin was similar to placebo, and it was supported by real-world data in a broad population of patients with T2DM, making DPP-4 inhibitors, like vildagliptin, a safe option for managing patients with T2DM.

Effectiveness, Safety and Tolerability of Vildagliptin with or without Metformin in Bangladeshi Patients with Type 2 Diabetes Mellitus: Results from Real-Life Observational Study

Background: Type 2 diabetes mellitus (T2DM) is a progressive disease which needs prolonged management with anti-diabetic drugs. The purpose of the present study was to assess effectiveness, safety and tolerability of treatment by vildagliptin alone or with the combination of vildagliptin and metformin in T2DM patients in a real-world setting.Methods: This non-interventional, prospective, multi-center study was conducted in several hospitals in Bangladesh from 15th September 2010 to 12th June 2012. Both male and female patients, aged ?18 years with an established diagnosis of T2DM, who had been prescribed vildagliptin or vildagliptin added to metformin free-dose or single-pill combination according to local prescribing information and who consented to data collection, were eligible for inclusion in the study. During the observational period of 24±6 weeks, data from three routine clinic visits were recorded; i.e. the baseline visit (Day 1), visit 2 (week 12±4 weeks) and a final visit (visit 3) at the end of the study (week 24±6 weeks).Result: A total number of 510 patients were enrolled in this study of which 468 patients were analyzed for the study and the remaining 42 patients were lost to follow up. Patients in vildagliptin group were treated with vildagliptin as monotherapy which was received by 101 patients; however, patients in vildagliptin/metformin group received the combination of vildagliptin and metformin which was in 367 cases. In vildagliptin group, the mean HbA1c was reduced from baseline (8.50±1.02 %) to 24 week (7.19±0.74%) (p&lt;0.0001). Similarly, in vildagliptin group the mean HbA1c at week 12 (7.76±0.96 %) was lower vs. baseline (8.50±1.02 %) (p&lt;0.0001). In vildagliptin and metformin combination group, the mean HbA1c at week 24 (7.02±0.66%) was lower vs. baseline (8.55±0.75%) (p&lt;0.0001). There were no deaths and no serious adverse effects. None of the patients reported any hypoglycemic event.Conclusion: In conclusion vildagliptin treating T2DM patients with or without metformin is associated with a significant and clinically relevant improvement in glycaemic control. Furthermore, vildagliptin treatment is generally well toleratedBirdem Med J 2016; 6(1): 12-17

Effects of vildagliptin versus saxagliptin on daily acute glucose fluctuations in Chinese patients with T2DM inadequately controlled with a combination of metformin and sulfonylurea

Objective The present study aimed to compare the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and saxagliptin on 24 hour acute glucose fluctuations in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with a combination of metformin and sulfonylurea.Research design and methods This was a 24 week, prospective, randomized, open-label, active-controlled study. Patients (N = 73) with T2DM who had inadequate glycemic control (HbA1c 7.0%–10.0%) with a stable dosage of metformin plus gliclazide for more than 3 months were randomized to receive either vildagliptin 50 mg twice daily (BID, n = 37) or saxagliptin 5 mg once daily (QD, n = 36). Change in mean amplitude of glycemic excursions (MAGE) was assessed at the end of 24 weeks.Results At baseline, the mean (±SD) age was 62.9 ± 6.55 years, disease duration was 7.0 ± 2.33 years, and HbA1c was 8.4 ± 0.68%. After 24 weeks of treatment, the MAGE decreased from 5.81 ± 1.16 mmol/L to 4.06 ± 0.86 mmol/L (p<0.001) in the vildagliptin group and from 5.66 ± 1.14 mmol/L to 4.79 ± 1.25 mmol/L (p = 0.003) in the saxagliptin group. The mean change in MAGE in the vildagliptin group was significantly greater than that in the saxagliptin group (1.74 ± 0.48 mmol/L vs. 0.87 ± 0.40 mmol/L, p<0.001). The mean change in HbA1c, from baseline to the study endpoint, in the vildagliptin and saxagliptin groups, was 1.22 ± 0.40% and 1.07 ± 0.36%, respectively, with no significant difference between the groups (p = 0.091). The overall safety and tolerability of vildagliptin and saxagliptin were similar. The limitations of the study were a small number of patients and open-label administration of the study drug.Conclusion Vildagliptin produced a significantly greater reduction in acute glucose fluctuations compared with saxagliptin when added to a dual combination of metformin and sulfonylurea in Chinese patients with T2DM.Chinese clinical trial registration number ChiCTR-TRC-13003858.

Efficacy and tolerability of vildagliptin as first line treatment in patients with diabetes type 2 in an outpatient setting.

BackgroundInhibitors of dipeptidyl-peptidase IV are recommended as second-line therapy in type 2 diabetes (DT2), but data, as a first-line treatment in everyday clinical practice are scarce. To address this issue we conducted a 12-month, clinical study in an outpatient setting, using vildagliptin as the first-line treatment.MethodsNinety-one drug naïve patients with DT2 started with vildagliptin monotherapy (100 mg daily) for 4 months and were scheduled to regular 4-monthly visits for 1 year. Patients received add-on treatment with metformin or metformin and glimepiride according to their glycosylated hemoglobin (HbA1c) at each study-visit.ResultsHbA1c was significantly decreased with vildagliptin monotherapy from 8.16 % ± 1.60 to 7.52 % ± 1.60, p < 0.001. Only 39 % of the patients achieved the target of HbA1c ≤ 7.0 % at the end of the 4th month. Mean change in HbA1c was significantly correlated with baseline HbA1c values (r = −0.51, p < 0.001). At the end of the study only 35 % of the patients remained on vildagliptin monotherapy while the rest required add-on treatment with metformin or metformin and sulfonylurea.ConclusionsVildagliptin is well tolerated either as monotherapy or in combination but the majority of patients require add-on therapy shortly after the beginning of treatment.

Clinical effectiveness and safety of vildagliptin in >19 000 patients with type 2 diabetes: the GUARD study.

The present GUARD study was a prospective, non-interventional study evaluating the clinical effectiveness, safety and tolerability of vildagliptin with or without metformin in adult patients with type 2 diabetes mellitus (T2DM) studied in routine clinical practice. Patients were enrolled from countries across four geographical regions. The primary endpoint was change in glycated haemoglobin (HbA1c) concentration from baseline after 24 weeks of treatment with vildagliptin with or without metformin. Of 19 331 patients analysed, 3511 received vildagliptin and 15 820 received vildagliptin plus metformin. At week 24, the mean HbA1c was reduced significantly from baseline by -1.27% (vildagliptin: -1.17%; vildagliptin plus metformin: -1.29%; p < 0.0001). Significant reductions in HbA1c from baseline were consistently reported regardless of patient age, body mass index (BMI) or baseline HbA1c. Weight and BMI were also significantly reduced from baseline. Vildagliptin treatment with or without metformin was generally well tolerated. It provided clinically relevant glycaemic and weight control, and was well tolerated in a large multi-ethnic population of patients with T2DM studied in routine clinical practice.

Use of Vildagliptin in Management of Type 2 Diabetes: Effectiveness, Treatment Persistence and Safety from the 2-Year Real-Life VILDA Study.

IntroductionThere is an increasing interest for real-life data on drug use in many countries. Reimbursement authorities more and more request observational studies to assess the conditions of use of the products but also to improve knowledge about efficacy and safety in the real world and on a longer term than in clinical trials.AimTo evaluate the effectiveness, treatment persistence and tolerability of vildagliptin in clinical practice.MethodsThis observational, 2-year prospective cohort study was conducted in France on request of the Health Authorities [Haute Autorite de Sante (HAS)]. Type 2 diabetic mellitus (T2DM) patients initiating vildagliptin (including the fixed combination vildagliptin-metformin) or treated for <6 months were recruited through a national representative sample of general practitioners (GPs) (n = 482) and diabetologists (n = 84) between March 2010 and December 2011. At inclusion and each follow-up visit at ~ 6, 12, 18 and 24 months, a questionnaire was completed by the physician collecting information on socio-demographic, clinical and biological data, treatments and adverse events.Results1,700 patients were included: 60% were males, aged 63 ± 11 years, with diabetes duration 7 ± 6 years and body mass index (BMI) 30 ± 6 kg/m2. 45% were obese, 70% treated for hypertension and 66% for dyslipidemia. 64% of the patients received vildagliptin in dual therapy with metformin. 82% of patients completed the 2-year follow-up. Glycosylated hemoglobin (HbA1c) decreased from a mean baseline of 7.8 ± 1.2% when vildagliptin was started, to 7.0 ± 1.1% at 6 months and remained stable thereafter over 2 years. Mean weight, glomerular filtration rate, liver enzymes, and lipid parameters were unchanged over the study period. Eight patients (0.5%), all concomitantly treated with insulin and/or sulphonylureas, reported one severe hypoglycemia and 47 (2.9%) patients reported 64 non-severe symptomatic hypoglycemia (59% occurred when patients were treated with insulin and/or sulphonylureas). At 6 months, 44.9% of vildagliptin-treated patients reached an HbA1c <7% without hypoglycemia and no weight gain, and this percentage increased to 49.7% at 24 months. Vildagliptin treatment maintenance at 2 years was 88.8% [95% CI (87.2%; 90.4%)], with 4% of patients discontinuing for adverse events.ConclusionsIn everyday conditions of care, vildagliptin efficacy was in line with existing data from randomized clinical trials, sustained over 2 years, with low discontinuation rate and low hypoglycemia risk.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0064-0) contains supplementary material, which is available to authorized users.

Effectiveness and tolerability of second-line therapy with vildagliptin versus other oral agents in type 2 diabetes (EDGE): post-hoc subanalysis of the Belgian data

Aim:To assess the efficacy and safety of vildagliptin versus other oral glucose-lowering drugs added to antidiabetic monotherapy in Belgian patients with type 2 diabetes mellitus, in comparison to the global EDGE study results.Methods:This is a pre-specified post-hoc subanalysis of the Belgian patient cohort from a worldwide 1-year observational study that compared the effectiveness and tolerability of vildagliptin to other oral antidiabetic agents in type 2 diabetes patients failing monotherapy with oral glucose-lowering agents (EDGE). A total of 1793 Belgian patients were enrolled. Physicians could add any oral antidiabetic drug and patients entered either into the vildagliptin or the comparator cohort. The primary effectiveness and tolerability endpoint was defined as the proportion of patients having a treatment response (HbA1c reduction from baseline to month 12 endpoint >0·3%) without hypoglycemia, weight gain, peripheral oedema, or gastrointestinal side-effects.Results:In the Belgian population, 37·8% of patients in the vildagliptin group and 32·8% in the comparator group had a decrease in HbA1c of >0·3% without the predefined tolerability issues of hypoglycemia, weight gain, oedema or, gastrointestinal complaints (primary endpoint), resulting in an unadjusted odds ratio of 1·24 (95% CI: 0·96–1·61). Mean HbA1c change from baseline was −0·81% in the vildagliptin cohort and −0·75% in the comparator cohort. Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (14·9% versus 14·5% in the compactor group) and serious adverse events (2·7% versus 2·5% in the comparator group).Conclusion:In this EDGE subgroup of Belgian patients with type 2 diabetes who do not achieve the glycemic targets with monotherapy, a similar trend as in the global EDGE study was observed. Adding vildagliptin as a second oral glucose-lowering agent resulted in lowering HbA1c to <7% without weight gain, hypoglycemia or peripheral oedema in a higher proportion of patients than comparator oral antidiabetic drugs, with no differences in the reported number of adverse events.

Real-Life Effectiveness and Tolerability of Vildagliptin and Other Oral Glucose-Lowering Therapies in Patients with Type 2 Diabetes in Germany

IntroductionMetformin is an established first-line treatment for patients with type 2 diabetes mellitus (T2DM), but treatment intensification with other oral antidiabetes drugs (OADs) is usually required over time. Effectiveness of diabetes control with vildagliptin and vildagliptin/metformin was a 1-year, large observational study of 45,868 patients with T2DM across 27 countries which assessed effectiveness and safety of vildagliptin as add-on therapy to other OADs versus other comparator OAD combinations. Here, we present the data from Germany.MethodsPatients inadequately controlled with monotherapy were eligible only after the add-on treatment was finalized. Patients were assigned to either vildagliptin or comparator OADs [sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors or metformin, excluding dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon-like peptide-1 mimetic/analogues]. The primary efficacy endpoint was the proportion of patients achieving a glycosylated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event or weight gain ≥5%. One secondary efficacy endpoint was the proportion of patients achieving HbA1c <7% without hypoglycemia and weight gain. Change in HbA1c from baseline to study endpoint and safety were assessed.ResultsOf 8,887 patients enrolled in Germany, 6,679 received vildagliptin and 1,695 received other OADs. The mean ± SD baseline age, HbA1c, and T2DM duration were 62.8 ± 11.0 years, 7.7 ± 1.2%, and 5.8 ± 4.9 years, respectively. The proportion of patients achieving the primary (34.5% vs. 30.5%, p < 0.01) and secondary (25.4% vs. 21.7%, p = 0.01) endpoints was higher with vildagliptin than comparator OADs. Vildagliptin showed a numerically greater reduction in HbA1c (0.7%) from baseline vs. comparator OADs (0.6%). The overall incidence of adverse events was similar.ConclusionIn real life, treatment with vildagliptin is associated with a higher proportion of patients reaching target HbA1c without hypoglycemia and weight gain compared with other OADs in Germany.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-014-0060-4) contains supplementary material, which is available to authorized users.

Vildagliptin: A Review of Its Use in Type 2 Diabetes Mellitus

The dipeptidyl peptidase-4 inhibitor vildagliptin (Galvus®) is approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. A fixed-dose combination of vildagliptin/metformin (Eucreas®) is also available. This article reviews the clinical efficacy and tolerability of vildagliptin in the treatment of type 2 diabetes, as well as summarizing its pharmacological properties. Results of randomized controlled trials demonstrated that oral vildagliptin improved glycaemic control when administered as monotherapy, as dual therapy in combination with metformin, a sulfonylurea or a thiazolidinedione, as triple therapy in combination with metformin plus a sulfonylurea, and in combination with insulin with or without metformin. Improvements in glycaemic control were also seen with vildagliptin in elderly patients with type 2 diabetes and in patients with type 2 diabetes and moderate or severe renal impairment. Vildagliptin was generally well tolerated in patients with type 2 diabetes, was weight neutral and was associated with a low risk of hypoglycaemia, reflecting its glucose-dependent mechanism of action. Thus, oral vildagliptin is a useful option as monotherapy or as add-on therapy for patients with type 2 diabetes.

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

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). 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. 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. 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.