Combination Of Vildagliptin Research Articles

Patient Profiling and Outcome Assessment of Vildagliptin and Dapagliflozin FDC in Persons with Type 2 Diabetes Mellitus

Introduction: Type 2 Diabetes Mellitus (T2D) is a condition characterized by rapid progression, and in certain instances, managing glucose levels may not be adequately achieved with a single pill. Vildagliptin and dapagliflozin in a Fixed-Dose Combination (FDC) complement each other’s actions, aiding in the control of glycemia. The primary goal of this retrospective investigation was to gain insight into the patient characteristics, safety profile, and efficacy of the FDC in reducing weight and glycated hemoglobin levels. Methods: Retrospective data from T2D patients who were prescribed the FDC and had two follow-up visits between May 1, 2022, and January 31, 2023, were enrolled in the study. Results: The average age of the study sample was 55.8 years, with nearly two-thirds being male (65.5%). At 6 months after FDC medication, glycated hemoglobin (HbA1c) significantly decreased by 1.2% (Baseline: 8.4%, Follow-up: 7.2%, p-value <0.001), indicating improved glycemic control. An average weight decrease of 4.3 kg (Baseline: 76.9Kg, Follow-up: 72.5Kg, p-value <0.001), was noted in patients receiving the FDC. Weight loss was higher in males (4.5 kg) than in females (4.0 kg). Safety analysis was carried out for all randomized patients and no major AEs were noted. No patients were withdrawn from the study due to safety concerns. No episode of hypoglycemia occurred during the study time. There were no statistical differences in the hepatic enzymes at the end of six months in the study groups. Conclusion: The Fixed Dose Combination of Vildagliptin and Dapagliflozin effectively enhances glycemic control by demonstrating a significant reduction in mean HbA1c levels after six months compared to baseline. However, further multicenter studies are necessary to substantiate these findings.

Formulation, characterization and evaluation of vildagliptin and metformin combined tablets

The current study was conducted to formulate and assess combined vildagliptin (VD) and metformin hydrochloride (MET) tablets. The formulations were developed by wet granulation to overwhelm the reduced compressibility of MET powder. Polymers like Kollidon K30 and K90 were used to prepare formulations. Micromeritics characteristics of blends were assessed. Subsequently, the tablets that had been manufactured were assessed for post-compression characteristics. The composition formula F7 was optimal due to having the best hardness, friability and good dissolution.

Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergometformin monotherapy.This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

A novel therapeutic combination of vildagliptin and agomelatine alleviates the nephropathy in streptozocininduced diabetic rats: A structural &amp; biochemical study

A novel therapeutic combination of vildagliptin and agomelatine alleviates the nephropathy in streptozocininduced diabetic rats: A structural &amp; biochemical study

Cost Utility Analysis Vildagliptin dan Glimepiride dalam Mencegah Komplikasi Mikrovaskuler menggunakan Model Markov

Microvascular complications can occur due to type 2 diabetes mellitus (DM). The cost of therapy increases due to the use of various antidiabetic drugs over a long period. This research is a pharmacoeconomic study that uses the Markov Model to compare costs and utilities in type 2 DM patients who receive metformin+glimepiride and metformin+vildagliptin therapy. Primary data was collected through the EQ5D questionnaire at Cirebon Harbor Hospital and secondary data (transition probability) was collected through a literature study. Characteristics of type 2 DM patients show that the majority of people suffering from this condition are aged between 55 and 59 years. Primary data from the hospital shows that the cost of therapy for controlled type 2 DM patients who receive combination therapy of metformin + glimepiride, and metformin + vildagliptin is Rp. 1,699,400, Rp. 5,807,786, and Rp. 10,100,426, respectively. Secondary data from articles treating type 2 DM shows that the 55-59 year age group is the largest. With an ICER of 61,493,943/QALYS, microvascular prevention in T2DM patients receiving the metformin+vildagliptin combination in Indonesia is considered effective and able to reduce the number of microvascular cases. This is based on the ICER value compared to the Indonesian Government's GDP, namely Rp. 71,030,183.3. This study shows that replacing glimepiride with vildagliptin for the prevention of microvascular complications is cost-effective and has better utility and effectiveness in reducing the incidence of microvascular complications. The use of vildagliptin can be recommended to reduce costs and the risk of microvascular complications.

Real-World Observational Study on Vildagliptin With Insulin (VIL-INS) or Vildagliptin and Metformin With Insulin (VIL-MET-INS) Therapy in Indian Patients With Type 2 Diabetes Mellitus.

The therapeutic use of vildagliptin and insulin (VIL-INS) or vildagliptin and metformin in combination with insulin (VIL-MET-INS) in the Indian scenario has yet to be explored by generating real-world evidence. Therefore, the present study aimed to evaluate the demographic, clinical characteristics, and treatment patterns of patients with type 2 diabetes mellitus (T2DM) in Indian settings in the above context. This observational study conducted at 600 healthcare centers in India retrospectively analyzed data of adult patients with T2DM who had been treated with either vildagliptin with insulin or a combination of vildagliptin and metformin with insulin. Data were collected from medical records and analyzed by appropriate statistical tests. A total of 12,603 patients with T2DM were included with a mean age of 53.4 years of which 63.8% were males. The majority of patients (n=6511; 51.7%) received a combination of vildagliptin and metformin on top of insulin. A significantly high proportion of patients in the age group of 18-40 years received this treatment compared to patients who were initiated on insulin treatment after vildagliptin and metformin combination (11.6% vs. 9.7%; P<0.001). Of all the patients, 70.0% were able to achieve target glycemic control with either VIS-INS or VIL-MET-INS. After treatment with VIL-INS or VIL-MET-INS, the mean glycated hemoglobin (HbA1c) levels significantly decreased with a mean change of 1.46%. Out of all patients, 13.5% experienced weight changes during treatment, with 67.4% of them showing weight loss. A total of 68 patients reported hypoglycemic events and among them, 49 patients had mild hypoglycemic events. Physician global evaluation of efficacy and tolerability showed a majority of patients rated their experience as good to excellent (86.3% and 86.0%, respectively). Both treatment regimens wereeffective in terms of reduced HbA1c to achieve glycemic control. Furthermore, it is well tolerated without an increase in the risk of hypoglycemia or weight gain. Hence, this therapy has favorable outcomes for T2DM management in Indian clinical settings.

Simultaneous Chromatographic Estimation of Vildagliptin and Dapagliflozin Using Hybrid Principles of White Analytical Chemistry and Analytical Quality by Design.

The fixed-dose combination of vildagliptin (VDG) and dapagliflozin (DGZ) is used in the treatment of type 2 diabetes mellitus. According to the literature survey, RP-HPLC and HPTLC methods have been reported for routine analysis of VDG and DGZ. These chromatographic methods have been developed using potentially neurotoxic and teratogenic solvents, which are unsafe for human and aquatic animal life and hazardous to the environment. These types of organic solvents shall be replaced or reduced during chromatographic analysis of drugs for the safety of human and aquatic animal life and the protection of the environment. The novel white analytical chemistry (WAC) approach has been introduced, which emphasizes robust, green, user-friendly, economical, and rapid analysis of drug samples. Hence, the WAC-based RP-HPLC method has been developed for the estimation of VDG and DGZ using lower toxic and economical solvents. The development of the RP-HPLC method includes the implementation of the analytical quality by design approach using principles of design of experiments to reduce organic waste generation and regulatory compliance of analytical method. The central composite design was applied for response surface modeling (RSM) and optimization of the RP-HPLC method. The method validation was carried out according to ICH Q2 (R1) guidelines. The fixed-dose combinations of VDG and DGZ were assayed, and results were found in compliance with their labeled claim. The published and proposed RP-HPLC methods were assessed for chromatographic analysis of VDG and DGZ using the Red-Green-Blue (RGB) model, AGREE calculator, Eco-Scale Assessment tool, GAPI software, and NEMI standards. The proposed method was found to be robust, green, economical, and user-friendly for chromatographic analysis of VDG and DGZ. The proposed method can be an economical and eco-friendly analytical tool in the pharmaceutical industry for quality control and routine analysis of fixed-dose combinations of VDG and DGZ. Hybrid principles of WAC and analytical quality by design to RP-HPLC method for simultaneous estimation of VDG and DGZ in their fixed-dose combinations.

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.

Effect of SGLT-2 inhibitor (remogliflozin) plus DPP4 inhibitor (vildagliptin) on diabetic nephropathy in patients with type 2 diabetes mellitus comparison with combination of metformin and sulphonylureas

Background: Diabetes is leading cause of renal failure in entire world. Approximately 20-40 percent of patients with diabetes develop diabetic nephropathy. Newer drugs like SGLT-2 inhibitors and DPP-4 inhibitors are valuable option for Diabetic Nephropathy. Remogliflozin etabonate (RE) is the latest addition to the SGLT2 inhibitor class of drugs that have been recently approved in India for the management of T2DM.This study was conducted to elaborate effect of SGLT2 inhibitor (remogliflozin) plus DPP4 inhibitor (vildagliptin) on diabetic nephropathy in patients of Type 2 DM. Methods: This hospital based, comparative, open label, randomized controlled trial has been carried out in our department during January 2020 to October 2022 on 60 patients. Group 1 was given metformin 500 mg BD and glimepiride 1 mg BD and group 2 was given FDC of remogliflozin 100 mg and vildagliptin 50 mg BD with 32 patients in group 1 and 28 patients in group 2. The study was approved by ethical committee of our institute. Results: Mean (SD) of urine ACR in metformin and glimepiride group at screening, 12 weeks, 24 weeks, and at 36 weeks were 93.64 (53.92), 95.56 (52.76), 89.96 (50.22) and 90.9 (53.56) respectively mean (SD) of urine ACR in remogliflozin and vildagliptin group at screening, 12 weeks, 24 weeks, and at 36 weeks were 108.28 (68.5), 100.73 (55.5), 99.35 (55.71) and 75.1 (38.7) respectively. Mean (SD) of eGFR in metformin and glimepiride group at screening, 12 weeks, 24 weeks, and at 36 weeks were 59.62 (18.57), 61.2 (11.1), 60.06 (14.37) and 60.8 (13.3) respectively. Mean (SD) of eGFR in remogliflozin and vildagliptin group at screening, 12 weeks, 24 weeks, and at 36 weeks were 68.03 (16.35), 65.8 (7.96), 66.28 (15.13) and 68.4 (11.6) respectively. Conclusions: Remogliflozin and vildagliptin combination has significant reduction of proteinuria and eGFR improvement when compared to metformin plus glimepiride.

Synergistic Benefits: Exploring the Anti-Virulence Effects of Metformin/Vildagliptin Antidiabetic Combination against Pseudomonas aeruginosa via Controlling Quorum Sensing Systems.

The repurposing of drugs is one of the most competent strategies for discovering new antimicrobial agents. Vildagliptin is a dipeptidyl peptidase-4 inhibitor (DPI-4) that is used effectively in combination with metformin to control blood glucose levels in diabetic patients. This study was designed to evaluate the anti-virulence activities of this combination against one of the most clinically important pathogens, Pseudomonas aeruginosa. The current findings show a significant ability of the vildagliptin-metformin combination to diminish biofilm formation, bacterial motility, and the production of virulent extracellular enzymes and pyocyanin pigment. Furthermore, this drug combination significantly increased the susceptibility of P. aeruginosa to oxidative stress, indicating immunity enhancement in the eradication of bacterial cells. In compliance with the in vitro findings, the histopathological photomicrographs of mice showed a considerable protective effect of the metformin-vildagliptin combination against P. aeruginosa, revealing relief of inflammation due to P. aeruginosa-induced pathogenesis. P. aeruginosa mainly employs quorum sensing (QS) systems to control the production of its huge arsenal of virulence factors. The anti-virulence activities of the metformin-vildagliptin combination can be interrupted by the anti-QS activities of both metformin and vildagliptin, as both exhibited a considerable affinity to QS receptors. Additionally, the metformin-vildagliptin combination significantly downregulated the expression of the main three QS-encoding genes in P. aeruginosa. These findings show the significant anti-virulence activities of metformin-vildagliptin at very low concentrations (10, 1.25 mg/mL, respectively) compared to the concentrations (850, 50 mg/mL, respectively) used to control diabetes.

749-P: Clinically Relevant Predictors of Cardiovascular Events: Exploratory Analysis from the VERIFY Study of Initial Treatment of Type 2 Diabetes Mellitus

The VERIFY study of primary treatment in type 2 diabetes mellitus (T2DM) , showed delayed glycemic failure (HbA1c ≥7.0% at two consecutive scheduled visits post randomization) with early combination of vildagliptin and metformin (EC) versus initial metformin monotherapy in patients with newly diagnosed T2DM (HbA1c 6.5%-7.5%) . Throughout the 5-year study, 57 adjudicated cardiovascular (CV) events were collected but the study was not powered to test the hypothesis that EC was also able to decrease CV events. Here we explore whether simple clinical data at T2DM onset (Framingham risk equation, CV disease history [CVD-Hx]) could identify patients at risk of subsequent CV events. At baseline, Framingham risk score (FRS) was 14.9±9.2% and 220 (12.3%) patients had CVD-Hx. A significant higher risk in patients with CVD-Hx and FRS ≥20% was visually apparent on KM curves and log rank-test (p=0.001; Figure) . Baseline HbA1c, age and gender were not significantly associated with the CV outcome, whereas treatment failure within the first 3 years was significantly associated with a higher risk of CV events (HR [95% CI]: 3.1 [1.7, 5.6]; p=0.0001) . These analyses suggests that both CV risk stratification at onset of T2DM and early loss of glycemic control may identify patients at higher risk of subsequent CV events. Disclosure D.R.Matthews: Advisory Panel; Novo Nordisk A/S, Other Relationship; Novartis AG, Speaker's Bureau; Servier Laboratories. S.Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. P.M.Paldanius: Consultant; Glyconics Ltd, UPM Biomedicals, Speaker's Bureau; Novartis AG, UPM Biomedicals. G.Bader: Employee; Novartis AG. Funding Novartis

Bioequivalence Studies of New Generic Formulations of Vildagliptin and Fixed-Drug Combination of Vildagliptin and Metformin Versus Respective Originator Products in Healthy Volunteers.

IntroductionVildagliptin and metformin are two well-established oral antidiabetics with a complementary mechanism of action. Two new generic products, vildagliptin and its fixed-drug combination (FDC) with metformin, were tested for bioequivalence versus the approved originator reference products (Galvus® and Eucreas®).MethodsThree randomized studies with two-treatment, two-period, two-sequence crossover design were conducted in healthy adults. One study evaluated vildagliptin 50 mg tablets as single dose under fasting conditions. Vildagliptin–metformin FDC tablet strengths of 50/850 mg and 50/1000 mg were evaluated in separate studies as single dose under fed conditions, given 30 min after a standardized high-fat, high-calorie breakfast following 10 h overnight fasting. Blood samples for analysis were collected until 24 h after dosing in each study period. Bioequivalence between test (T) and reference (R) products required 90% confidence interval (CIs) for the geometric least square (LS) mean T/R ratio to be within 80–125% for the pharmacokinetic parameters, maximum plasma concentration (Cmax), and area under the curve (AUC0–t).ResultsThe 90% CIs of geometric LS means of T/R ratio for Cmax and AUC0–t with vildagliptin tablets of 50 mg were 92.22–103.94% and 99.00–102.66%, respectively; corresponding results with FDC tablets for 50/850 mg tablets were 94.81–115.41% and 95.28–106.00% for vildagliptin and 90.87–101.18% and 90.56–100.09% for metformin; for 50/1000 mg tablets Cmax and AUC0–t were 105.56–122.30% and 98.30–107.55%, respectively, for vildagliptin and 92.14–103.73% and 94.60–101.81%, respectively, for metformin. Other parameters such as AUC0–∞, time to maximum concentration (Tmax), and terminal half-life (t1/2) were comparable between test and reference products. Adverse events (AEs), mainly vomiting, were reported without relevant difference between test and reference products in each study. AEs were generally mild and transient. No severe or serious AEs occurred.ConclusionsThe new generic drug products of vildagliptin and the FDCs of vildagliptin and metformin demonstrated bioequivalence to the approved originator products and are therefore expected to provide similar therapeutic effects.

Exploring early combination strategy in Latin American patients with newly diagnosed type 2 diabetes: a sub-analysis of the VERIFY study

BackgroundPatients with type 2 diabetes mellitus (T2DM) from Latin American countries face challenges in access to healthcare, leading to under-diagnosis, under-achievement of glycemic target, and long-term complications. Early diagnosis and treatment initiation are of paramount importance in this population due to the high prevalence of risk factors such as obesity and metabolic syndrome. The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET). Here we present the results from the VERIFY study for participants from eight countries in Latin America.MethodsNewly diagnosed adult patients with T2DM, HbA1c 6.5–7.5% and body-mass index (BMI) of 22–40 kg/m2 were enrolled. The primary endpoint was time to initial treatment failure (TF; HbA1c ≥ 7.0% at two consecutive scheduled visits 13 weeks apart). Time to second TF was evaluated when patients in both groups were receiving and failing on the vildagliptin combination. Safety and tolerability were also assessed for both treatment approaches during the study.ResultsA total of 537 eligible patients (female, 58.8%) were randomly assigned to receive either EC (n = 266) or MET (n = 271). EC significantly reduced the relative risk of time to initial TF by 47% versus MET [HR (95% CI) 0.53 (0.4, 0.7) p < 0.0001]. Overall, 46.4% versus 66.3% of patients achieved the primary endpoint in the EC and MET groups, with a median [interquartile range (IQR)] time to TF of 59.8 (27.5, not evaluable) and 33.4 (12.2, 60.1) months, respectively. The risk for time to second TF was 31% lower with EC (p < 0.0092). A higher proportion of patients receiving EC maintained durable HbA1c < 7.0%, < 6.5%, and < 6.0%. Both treatment approaches were well tolerated, and only 3.2% of participants discontinued the study due to adverse events. All hypoglycemic events (EC: n = 7 and MET: n = 3) were single, mild episodes and did not lead to study discontinuation.ConclusionSimilar to the global population, long-term clinical benefits were achieved more frequently and without tolerability issues with EC versus standard-of-care MET in this Latin American sub-population.This study is registered with ClinicalTrials.gov, NCT01528254.

Abstract #1004069: Effectiveness of Remogliflozin and Vildagliptin Combination in Type 2 Diabetes Mellitus Patients Uncontrolled on Triple Oral Drug Therapy

Abstract #1004069: Effectiveness of Remogliflozin and Vildagliptin Combination in Type 2 Diabetes Mellitus Patients Uncontrolled on Triple Oral Drug Therapy

Data on vildagliptin and vildagliptin plus metformin combination in type-2 diabetes mellitus management

It is of interest to evaluate the clinical effectiveness and safety of vildagliptin as monotherapy and combination therapy of vildagliptin and metformin for the management of type 2 diabetes mellitus (T2DM) patients in Indian settings. The study included patients with T2DM (aged &gt;18 years) receiving vildagliptin monotherapy and vildagliptin in combination with metformin therapy of various strengths. Data related to demographics, risk factors, medical history, glycated hemoglobin (HbA1c) levels, and medical therapies were retrieved from medical records. Out of 9678 patients (median age, 52.0 years), 59.1% were men. A combination of vildagliptin and metformin (50/500 mg) was the most commonly used therapy (54.8%), and the median duration of therapy was 24.0 months. The predominant reason for selecting vildagliptin therapy was to improve HbA1c levels (87.8%). A total of 87.5% of patients required dosage up-titration. Vildagliptin therapy was used in patients with T2DM and associated complications (peripheral neuropathy, CAD, nephropathy, retinopathy, autonomous neuropathy, stroke/TIA, and peripheral artery disease). Among 5175 patients who experienced body weight changes, a majority of patients had lost weight (68.6%). The target glycemic control was achieved in 95.3% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.34%; p&lt;0.001). Adverse events were reported in 0.4% of patients. Physicians rated the majority of patients as good to excellent on the global evaluation of efficacy and tolerability scale (98.9%, each). Vildagliptin with or without metformin was an effective therapy in reducing HbA1c helps in achieving target glycemic control, and was well-tolerated in Indian patients with T2DM continuum.

Data on vildagliptin and vildagliptin plus metformin combination in type-2 diabetes mellitus management.

It is of interest to evaluate the clinical effectiveness and safety of vildagliptin as monotherapy and combination therapy of vildagliptin and metformin for the management of type 2 diabetes mellitus (T2DM) patients in Indian settings. The study included patients with T2DM (aged >18 years) receiving vildagliptin monotherapy and vildagliptin in combination with metformin therapy of various strengths. Data related to demographics, risk factors, medical history, glycated hemoglobin (HbA1c) levels, and medical therapies were retrieved from medical records. Out of 9678 patients (median age, 52.0 years), 59.1% were men. A combination of vildagliptin and metformin (50/500 mg) was the most commonly used therapy (54.8%), and the median duration of therapy was 24.0 months. The predominant reason for selecting vildagliptin therapy was to improve HbA1c levels (87.8%). A total of 87.5% of patients required dosage up-titration. Vildagliptin therapy was used in patients with T2DM and associated complications (peripheral neuropathy, CAD, nephropathy, retinopathy, autonomous neuropathy, stroke/TIA, and peripheral artery disease). Among 5175 patients who experienced body weight changes, a majority of patients showed a loss of weight (68.6%). The target glycemic control was achieved in 95.3% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.34%; p<0.001). Adverse events were reported in 0.4% of patients. Physicians rated the majority of patients as good to excellent on the global evaluation of efficacy and tolerability scale (98.9%, each). Vildagliptin as monotherapy and combination therapy of vildagliptin and metformin was an effective therapy in reducing HbA1c helps in achieving target glycemic control, and was well tolerated in Indian patients with T2DM continuum.

Dynamics of total volume of pancreatic α- and β -cells under the influence sulfonylureas and their combination with dipeptidyl peptidase-4 inhibitors.

ObjectiveSulfonylureas and dipeptidyl peptidase‐4 inhibitors have a multidirectional effect on pancreatic cells. We aimed to evaluate the effects of these drugs on β‐ and α‐cells in rats aged 12 months with type 2 diabetes mellitus when administered in combination with various sulfonylureas.MethodsStreptozotocin‐nicotinamide induced type 2 diabetes mellitus was induced in rats aged 12 months. Animals received the sulfonylureas gliclazide or glibenclamide for 24 weeks alone or in combination with the dipeptidyl peptidase‐4 inhibitor vildagliptin or vildagliptin monotherapy. Blood glucose and animal weights were measured before and during the experiment. The oral glucose tolerance test was conducted before therapy initiation. Immunohistochemical analyses were conducted after the end of the experiment using glucagon and insulin antibodies. The total volumes of α and β cells were estimated in relation to the volume of the pancreatic islets.ResultsThe total volumes of β‐cells did not differ between the sulfonylurea group and the untreated type 2 diabetes mellitus group. The addition of dipeptidyl peptidase‐4 inhibitors to sulfonylureas normalized the total volumes of β cells. The total volumes of α‐cells in the gliclazide group and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor was comparable to that in the control group of intact animals, in contrast with the glibenclamide group.ConclusionThe combination of vildagliptin to both sulfonylureas contributed to the normalisation of β‐cells number. Normalisation of the total volumes of α‐cells was observed with gliclazide therapy and combination of gliclazide with dipeptidyl peptidase‐4 inhibitor.

Early intensification of glucose-lowering therapy: VERIFY lessons and real clinical practice on the example of the Moscow region diabetes register data

The prevalence of T2DM is steadily increasing not only among the elderly, but also at a young age. T2DM is preceded by a long period of significant metabolic changes with the development of insulin resistance and в-cell dysfunction. To reduce the prevalence of complications, treatment is needed which affects several pathophysiological mechanisms underlying the disease. Monotherapy with metformin at the onset of T2DM is often insufficient. The VERIFY study demonstrated the advantage of early administration of a combination of vildagliptin and metformin in relation to the glycemic durability compared to the sequential intensification of metformin with vildagliptin in patients with type 2 diabetes. To assess the current situation in terms of the incidence of T2DM complications and the structure of the prescribing glucose lowering drugs based on the data from the Diabetes Register (DR) of the Moscow Region. To demonstrate the advantages of early combination therapy in patients with newly diagnosed T2DM using clinical cases. The data from the DR of the Moscow region, which is part of the National Diabetes Register of the Russian Federation, were used for the analysis. The data of 6,096 patients with T2DM who died in 2019 were evaluated for building the structure of the causes of death of patients with T2DM. The pattern of glucose-lowering therapy was analyzed based on data of 226,327 patients with T2DM (for 2020), as well as separately of 14,379 patients with newly diagnosed T2DM in 2019. Clinical cases are described based on the data of two patients with T2DM, available in the DR database and outpatient records. In patients with young onset T2DM (&lt;40 years), the prevalence of severe complications is higher than in the general population of patients with T2DM: blindness is in 5.9 times, end-stage chronic renal failure in 2.9 times, lower limb amputations in 6.4 times more. When prescribing glucose lowering drugs, monotherapy is prevalent, mostly metformin. In double combination, metformin is used in 96.22% of cases. In the structure of glucose lowering drugs, with newly diagnosed T2DM, combination therapy is used less frequently than in patients with T2DM in general. Of the drugs of the IDP-4 group, vildagliptin is most often prescribed - 46.25% (including of a fixed combination with metformin - 12.22%). Clinical cases reflect a rapid clinical outcome: a decrease in HbA1c to the target in 6 months, the absence of hypoglycemia or other side effects, and positive weight dynamics. A fairly large propotion of patients with T2DM are on monotherapy with glucouse lowering drugs. Early prescription of the combination of metformin plus vildagliptin provides a longer maintenance of glycemic control without increasing the risk of hypoglycemia and weight gain for patients with newly diagnosed T2DM.

Safety and efficacy of vildagliptin: 52-week post-marketing surveillance of Japanese patients with type 2 diabetes in combination with other oral antidiabetics and insulin

ABSTRACT Background: Vildagliptin is a dipeptidyl peptidase-4 inhibitor that reduces glycemia in patients with type 2 diabetes mellitus (T2DM). When approved in 2013, data on vildagliptin combined with >750 mg/day metformin in Japanese patients were limited. There is a need to confirm the safety and efficacy of vildagliptin in combination with oral antidiabetic drugs (OADs). Research design and methods: This 52-week post-marketing surveillance (PMS) observational study in Japanese T2DM patients evaluated the safety and efficacy of vildagliptin in combination with OADs including high-dose metformin or insulin but excluding combination with sulfonylureas alone. Results: During this survey of 3006 Japanese T2DM patients, 13.61% of patients experienced adverse events (AEs) and 2.20% reported a serious AE (SAE). The frequency of AEs/SAEs was similar when in combination with biguanides (12.93%/1.46%), metformin ≥1000 mg/day (12.92%/1.22%), metformin <1000 mg/day (12.62%/1.54%), thiazolidine derivatives (16.71%/2.86%), α-glucosidase inhibitors (13.18%/1.90%), rapid-acting insulin secretagogues (glinides) (20.41%/5.71%), or insulin (15.87%/2.47%). The mean ± SD changes from baseline at endpoint in glycated hemoglobin and fasting blood glucose were −0.76 ± 1.27% and −23.3 ± 57.3 mg/dL, respectively, and these changes were consistent, regardless of concomitant OAD. Conclusions: Long-term vildagliptin combination therapy is safe and effective in Japanese T2DM patients in real-world settings.

Combined dipeptidyl peptidase-4 inhibitor with low-dose testosterone exerts greater efficacy than monotherapy on improving brain function in orchiectomized obese rats.

Both obesity and orchiectomy lead to the development of brain pathologies and cognitive decline. Testosterone replacement therapy (2 mg/kg/day TRT) and dipeptidyl peptidase-4 inhibitor (vildagliptin) improved cognition in orchiectomized rats, and obese rats. However, both had no beneficial effects in brain of orchiectomized-obese rats. TRT (>2 mg/kg/day) is possible to attenuate brain defects in those rats, but high dose of TRT causes adverse effects. Then, combined effect of low-dose TRT (1 mg/kg/day) and vildagliptin on brain and cognitive functions in orchiectomized-obese rats should be investigated. Sixty male rats were fed with either a normal diet (ND) or a high-fat diet (HFD) for 28 weeks. At week 13, both ND and HFD-fed rats had either a sham-operation or an orchiectomy. At week 25, orchiectomized rats were treated with either: a vehicle, 2 mg/kg/day TRT, vildagliptin (3 mg/kg/day) or a combined vildagliptin with 1 mg/kg/day TRT for 4 weeks. Then, metabolic parameters, brain and cognitive functions were determined. Hippocampal oxidative stress, apoptosis, dendritic spine loss, microglial hyperactivity, and cognitive decline were found in orchiectomized ND-fed rats and sham-operated HFD-fed rats. Interestingly, orchiectomy aggravated these brain pathologies and cognitive decline in HFD-fed rats. In orchiectomized ND-fed rats, all treatments restored brain and cognitive functions. In orchiectomized HFD-fed rats, monotherapies ameliorated these brain pathologies, while the combined therapies had the greatest beneficial effect on the brains. These findings suggest the combined therapies may be the best therapeutic approach for restoring brain functions in the orchiectomized-obese condition.