Vildagliptin 50mg tablets

BACKGROUND: Ramadan Iftar meal typically causes glucose excursions. Dipeptidyl peptidase-4 inhibitors increase glucagon-like peptide-1 and thus, decrease blood glucose levels with low risk of hypoglycemia. AIM: To investigate the efficacy and safety of vildagliptin as an add-on therapy on glucose excursions of Iftar Ramadan meals among adolescents and young adults with type 1 diabetes mellitus (T1DM) using advanced hybrid closed-loop (AHCL) treatment. METHODS: Fifty T1DM patients on MiniMed™ 780G AHCL were randomly assigned either to receive vildagliptin (50 mg tablet) with iftar meal during Ramadan month or not. All participants received pre-meal insulin bolus based on insulin-to-carbohydrate ratio (ICR) for each meal constitution. RESULTS: Vildagliptin offered blunting of post-meal glucose surges (mean difference - 30.3 mg/dL [- 1.7 mmol/L] versus - 2.9 mg/dL [- 0.2 mmol/L] in control group; p < 0.001) together with concomitant exceptional euglycemia with time in range (TIR) significantly increased at end of Ramadan in intervention group from 77.8 ± 9.6% to 84.7 ± 8.3% (p = 0.016) and time above range (180-250 mg/dL) decreased from 13.6 ± 5.1% to 9.7 ± 3.6% (p = 0.003) without increasing hypoglycemia. A significant reduction was observed in automated daily correction boluses and total bolus dose by 23.9% and 16.3% (p = 0.015 and p < 0.023, respectively) with less aggressive ICR settings within intervention group at end of Ramadan. Coefficient of variation was improved from 37.0 ± 9.4% to 31.8 ± 7.1%; p = 0.035). No severe hypoglycemia or diabetic ketoacidosis were reported. CONCLUSION: Adjunctive vildagliptin treatment mitigated postprandial hyperglycemia compared with pre-meal bolus alone. Vildagliptin significantly increased TIR while reducing glycemic variability without compromising safety. Trial registration This trial was registered under ClinicalTrials.gov Identifier no. NCT06021119.

Abstract licence: CC BY

Background: Understanding which group of patients with type 2 diabetes will have the most glucose lowering response to certain medications (which target different aspects of glucose metabolism) is the first step in precision medicine. Aims: We hypothesized that people with type 2 diabetes who generally have high insulin resistance, such as people of Māori/Pacific ethnicity, and those with obesity and/or hypertriglyceridemia (OHTG), would have greater glucose-lowering by pioglitazone (an insulin sensitizer) versus vildagliptin (an insulin secretagogue). Methods: A randomised, open-label, two-period crossover trial was conducted in New Zealand. Adults with type 2 diabetes, HbA1c>58mmol/mol (>7.5%), received 16 weeks of either pioglitazone (30mg) or vildagliptin (50mg) daily, then switched to the other medication over for another 16 weeks of treatment. Differences in HbA1c were tested for interaction with ethnicity or OHTG, controlling for baseline HbA1c using linear mixed models. Secondary outcomes included weight, blood pressure, side-effects and diabetes treatment satisfaction. Results: 346 participants were randomised (55% Māori/Pacific) between February 2019 to March 2020. HbA1c after pioglitazone was lower than after vildagliptin (mean difference -4.9mmol/mol [0.5%]; 95% CI -6.3, -3.5; p<0.0001). Primary intention-to-treat analysis showed no significant interaction effect by Māori/Pacific vs other ethnicity (1.5mmol/mol [0.1%], 95% CI -0.8, 3.7), and per-protocol analysis (-1.2mmol/mol [0.1%], 95% CI -4.1, 1.7). An interaction effect (-4.7mmol/mol [0.5%], 95% CI -8.1, -1.4) was found by OHTG status. Both treatments generated similar treatment satisfaction scores, although there was greater weight gain and greater improvement in lipids and liver enzymes after pioglitazone than vildagliptin. Conclusions: Comparative glucose-lowering by pioglitazone and vildagliptin is not different between Māori/Pacific people compared with other New Zealand ethnic groups. Presence of OHTG predicts greater glucose lowering by pioglitazone than vildagliptin. Clinical trial registration: www.anzctr.org.au, identifier (ACTRN12618001907235).

Abstract licence: CC BY

Dipeptidyl peptidase-4 inhibitors (DPP4Is) were introduced into the management of type 2 diabetes mellitus (T2DM) as they are insulinotropic and have no inherent risk of hypoglycemia and no effect on body weight. Currently, 11 drugs in this class are available for the management of diabetes. Although they have a similar mechanism of action, they differ from one other in their binding mechanisms, which influences their therapeutic and pharmacological profiles. Vildagliptin's overall safety and tolerability profile was comparable to placebo throughout clinical studies, and real-world data in a large group of T2DM patients corroborated this finding. Therefore, DPP4Is like vildagliptin is a secure alternative for treating patients with T2DM. Vildagliptin treatment given as a once-daily (QD) 100 mg sustained release (SR) formulation fits the criteria of adherence and compliance. This SR formulation, given once daily has the potential to provide glycemic control like the vildagliptin 50 mg twice-daily (BD) formulation. This comprehensive review discusses the journey of vildagliptin as 50 mg BD therapy as well as 100 mg SR QD therapy.

Abstract licence: CC BY

(1) Background: There is a high burden of poor glycemic control in the Indian population with type 2 diabetes mellitus (T2DM). Currently, the use of metformin sustained-release (SR)–vildagliptin fixed-dose combination (FDC) is very low as compared to metformin immediate-release (IR)–vildagliptin FDC which is associated with higher adverse events (AEs). Here, we present real-world effectiveness of metformin SR–vildagliptin FDC treatment in patients with T2DM; (2) Methods: This retrospective analysis was carried out from the medical records of adult T2DM patients visiting a single study center in India (December 2020–February 2021). A total of 10 patients (aged ≥20 years) were treated with vildagliptin 50 mg and metformin SR 500 mg FDC for 15 days. The treatment response was assessed by the percentage of time spent in the target glucose range (TIR at baseline and 15 days after treatment); (3) Results: The glycated hemoglobin (HbA1c) levels at baseline varied between 6.5% to 12%. The glycemic control improved in 70% of patients (mean increase in TIR: 18.9%). Treatment adherence was 100%. No gastrointestinal symptoms or AEs were reported; (4) Conclusions: Early intervention with metformin SR–vildagliptin FDC in patients with T2DM can ensure therapy compliance in terms of superior efficacy along with safety and tolerability. Key summary points: Early initiation of combination therapy helps in early achievement of glycemic goals; Early initiation of metformin and vildagliptin FDC results in significant glycemic control with good tolerability and compliance; Metformin SR–vildagliptin FDC has lower adverse events, compared to metformin IR–vildagliptin FDC; A case series of ten patients with T2DM treated with metformin SR–vildagliptin FDC is presented to assess the real-world effectiveness of this combination.

Abstract licence: CC BY

Diabetes mellitus (DM) is the most prevalent cause of diabetic retinopathy (DRP). DRP has been recognized for a long time as a microvascular disease. Many drugs were used to treat DRP, including vildagliptin (VLD). In addition to its hypoglycemic effect, VLD minimizes ocular inflammation and improves retinal blood flow for individuals with type 2 diabetes mellitus. Nevertheless, VLD can cause upper respiratory tract infections, diarrhea, nausea, hypoglycemia, and poor tolerability when taken orally regularly due to its high water solubility and permeability. Effective ocular administration of VLD is achieved using solid lipid nanoparticles (SLNPs), which improve corneal absorption, prolonged retention, and extended drug release. Ocuserts (OCUs) are sterile, long-acting ocular dosage forms that diminish the need for frequent dosing while improving residence time and stability. Therefore, this study intends to develop VLD solid lipid nanoparticle OCUs (VLD-SLNPs-OCUs) to circumvent the issues commonly associated with VLD. SLNPs were prepared using the double-emulsion/melt dispersion technique. The optimal formula has been implemented in OCUs. Optimization and development of VLD-SLNPs-OCUs were performed using a Box-Behnken Design (BBD). VLD-SLNPs-OCUs loading efficiency was 95.28 ± 2.87%, and differential scanning calorimetry data (DSC) showed the full transformation of VLD to an amorphous state and the excellent distribution in the prepared OCUs matrices. The in vivo release of VLD from the optimized OCUs after 24 h was 35.12 ± 2.47%, consistent with in vitro drug release data of 36.89 ± 3.11. The optimized OCUs are safe to use in the eye, as shown by the ocular irritation test. VLD-SLNPs-OCUs provide extended VLD release, an advantageous alternative to conventional oral dose forms, resulting in fewer systemic adverse effects and less variation in plasma drug levels. VLD-SLNPs-OCUs might benefit retinal microvascular blood flow beyond blood glucose control and may be considered a promising approach to treating diabetic retinopathy.

Abstract licence: CC BY-NC-ND

Cisplatin (CP) is a broad-spectrum antineoplastic agent used to treat many human cancers. Nonetheless, most patients receiving CP suffer from cognitive deficits, a phenomenon termed "chemo-brain". Recently, vildagliptin (Vilda), a DPP-4 inhibitor, has demonstrated promising neuroprotective properties against various neurological diseases. Therefore, the present study aims to investigate the potential neuroprotective properties of Vilda against CP-induced neurotoxicity and elucidate the underlying molecular mechanisms. Chemo-brain was induced in Sprague-Dawley rats by i.p injection of CP at a dose of 5 mg/kg once weekly for four weeks. Vilda was administered daily at a dose (10 mg/kg; P.O) for four weeks. The results revealed that Vilda restored the cognitive function impaired by CP, as assessed by the Morris water maze, Y-maze, and passive avoidance tests. Moreover, Vilda alleviated the CP-induced neurodegeneration, as shown by toluidine blue staining, besides markedly reduced amyloid plaque deposition, as evidenced by Congo red staining. Notably, Vilda boosted cholinergic neurotransmission through the downregulation of the acetylcholinesterase enzyme. In addition, the neuroprotective mechanisms of Vilda include diminishing oxidative stress by reducing MDA levels while raising GSH levels and SOD activity, repressing neuronal apoptosis as shown by elevated Bcl-2 levels together with diminished Bax and caspase-3 expressions, inhibiting neuroinflammation as shown by decreased GFAP expression, and finally boosting hippocampal neurogenesis and survival by upregulating expressions of BDNF and PCNA. These effects were mainly mediated by activating AMPK/Akt/CREB signaling cascades. In summary, Vilda can be considered a promising candidate for guarding against CP-induced chemo-brain and neurodegeneration, thus improving the quality of life of cancer patients.

Abstract licence: CC BY

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.

Abstract licence: CC BY