Linagliptin

BACKGROUND: Linagliptin is an oral dipeptidyl peptidase DPP-4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy with other hypoglycemic drugs. OBJECTIVES: We aimed to summarize the evidence from randomized controlled trials (RCTs) to assess the safety of linagliptin focusing on cardiovascular risks among subjects with type 2 diabetes mellitus. METHODS: We conducted a systematic search across the following databases: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials...

PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic drugs and are used for type II diabetes. Previous studies showed that DPP-4 expression is observed in several tumor types and DPP-4 inhibitors suppress the tumor progression on murine tumor models. In this study, we evaluated the role of DPP-4 and the antitumor effect of a DPP-4 inhibitor, linagliptin, on glioblastoma (GBM). METHODS: We analyzed DPP-4 expression in glioma patients by the public database...

To optimize the treatment plan for patients with type 2 diabetes mellitus (T2DM) and hyperuricemia, this narrative literature review summarizes the effect of antidiabetic drugs on serum uric acid (SUA) levels using data from observational studies, prospective clinical trials, post-hoc analyses and meta-analyses. SUA is an independent risk factor for T2DM, and evidence has shown that patients with both gout and T2DM exhibit a mutually interdependent effect on higher incidences. We find that insulin and dipeptidyl peptidase 4 inhibitor (DPP-4i) except linagliptin could increase the SUA, and other drugs including metformin, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), linagliptin, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and α-glucosidase inhibitors have a reduction effect on SUA...

The increasing occurrence of childhood overweight and obesity has been followed by a substantial increase in youth-onset type 2 diabetes (T2D). Pharmacological treatment options for youth-onset T2D remain limited, with a clear unmet need for additional oral agents. This summary of research reports on the efficacy and safety of empagliflozin and linagliptin on glycaemic control in children and adolescents aged 10-17 years with T2D in the randomised, double-blind, parallel group, phase 3 DINAMO trial. Empagliflozin provided a clinically relevant, statistically significant, and durable improvement in glycaemic control; however, linagliptin did not...

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid...

Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat-regulating peptides such as GLP-1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia...

A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP-4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug-drug interactions (DDIs) between PPIs (i...

Linagliptin is a dipeptidyl peptidase-4 inhibitor used for the management of type-2 diabetes. US FDA-approved products are available exclusively as oral tablets. The inherent drawbacks of the oral administration route necessitate exploring delivery strategies via other routes. In this study, we investigated the feasibility of transdermal administration of linagliptin through various approaches. We compared chemical penetration enhancers (oleic acid, oleyl alcohol, and isopropyl myristate) and physical enhancement techniques (iontophoresis, sonophoresis, microneedles, laser, and microdermabrasion) to understand their potential to improve transdermal delivery of linagliptin...

Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that indirectly elevates the glucagon-like peptide-1 (GLP-1) level. The aim of the present study was to check whether linagliptin has an influence on neurotransmission in rat brain. Rats were acutely and chronically exposed to linagliptin (10 and 20 mg/kg, intraperitoneally (i.p.)). Twenty-four hours later, the striatum and hippocampus were selected for further studies. In neurochemical experiments, using high-performance liquid chromatography with electrochemical detection (HPLC-ED), the concentrations of three major neurotransmitters-dopamine, serotonin and noradrenaline-and their metabolites were measured...

As part of the development and production of pharmaceuticals, the purity of Active Pharmaceutical Ingredients stands as a fundamental parameter that significantly influences the quality, safety, and efficacy of the final drug product. Impurities in Active Pharmaceutical Ingredients are various unwanted substances that can appear during the whole manufacturing process, from raw materials to the final product. These impurities can stem from multiple sources, including starting materials, intermediates, reagents, solvents, and even degradation products resulting from exposure to environmental factors such as heat, light, or moisture...

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants...

Gallic acid (GA), a dietary phenolic acid with potent antioxidant activity, is widely distributed in edible plants. GA has been applied in the food industry as an antimicrobial agent, food fresh-keeping agent, oil stabilizer, active food wrap material, and food processing stabilizer. GA is a potential dietary supplement due to its health benefits on various functional disorders associated with oxidative stress, including renal, neurological, hepatic, pulmonary, reproductive, and cardiovascular diseases. GA is rapidly absorbed and metabolized after oral administration, resulting in low bioavailability, which is susceptible to various factors, such as intestinal microbiota, transporters, and metabolism of galloyl derivatives...

OBJECTIVES: Uncertainties remain regarding the effect of elevated glucose levels on lymphatic metastasis of cancer cells. Our study elucidated the mechanisms linking high glucose to lymphangiogenesis and lymphatic barrier-related factors and investigated the protective role of linagliptin against lymphatic barrier dysfunction. MATERIALS AND METHODS: A CAL-27-LEC co-culture system was established. Sodium fluorescein permeability assay observed lymphatic endothelial cell permeability...

Uterine fibroid is the most common non-cancerous tumor with no satisfactory options for long-term pharmacological treatment. Fibroblast activation protein-α (FAP) is one of the critical enzymes that enhances the fibrosis in uterine fibroids. Through STITCH database mining, we found that dipeptidyl peptidase-4 inhibitors (DPP4i) have the potential to inhibit the activity of FAP. Both DPP4 and FAP belong to the dipeptidyl peptidase family and share a similar catalytic domain. Hence, ligands which have a binding affinity with DPP4 could also bind with FAP...

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies...

We describe two patients, in their 70s, each presenting to the emergency department, with 6-week histories of progressively developing pruritic bullae. Both individuals had multiple comorbidities, including type 2 diabetes-for which they took linagliptin, chronic kidney disease, hypertension and prosthetic heart valves. Owing to systemic illness and endocarditis secondary to superadded bacterial infections, they both required intensive treatment and prolonged hospital admissions.Despite the beneficial effect of linagliptin on glycaemic control and its reported cardiovascular and renal safety profiles, we add our cases as evidence of the significant risk of developing bullous pemphigoid while taking this medication...

Between February 2020 and January 2022, the Food and Drug Administration (FDA) recalled 281 metformin extended-release products due to the presence of N-nitrosodimethylamine (NDMA) above the acceptable daily intake (ADI, 96 ng/day). Our previous studies indicated presence of NDMA levels above ADI in both metformin immediate and extended-release products. When metformin products have NDMA impurities, it is indispensable to check for the same impurities in metformin combination products. Therefore, the objective of the present study was to evaluate in-use stability of commercial metformin combination products for NDMA...

BACKGROUND: Linagliptin (LNG) exhibits poor bioavailability and numerous side effects, significantly limiting its use. Transdermal drug delivery systems (TDDS) offer a potential solution to overcome the first-pass effect and gastrointestinal reactions associated with oral formulations. OBJECTIVE: The aim of this study was to develop LNG microparticle gels to enhance drug bioavailability and mitigate side effects. METHODS: Linagliptin hyaluronic acid (LNG-HA) microparticles were prepared by spray drying method and their formulation was optimized via a one-factor method...

Extensive preclinical evidence demonstrates a causative link between insulin signaling dysfunction and the pathogenesis of Alzheimer's disease (AD), and diabetic drugs may represent a promising approach to fighting AD. However, it remains to be determined which antidiabetic drugs are more effective in preventing cognitive impairment. Thus, the present study investigated the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on cognitive impairment in middle-aged mice by comparing it with the effect of metformin...

Metformin is considered as type 2 diabetes first line treatment according to American Diabetes Association and European Association. But, in some cases, di- or tri - therapy should be prescribed for glycemic management, prevention of the maximum dose side effects and induced effectiveness. Co-administration of Linagliptin with metformin has many benefits on diabetic patients such as decrease the possibility of hypoglycemia. For the first time, novel and reliable techniques were developed and verified for the concurrent quantification of metformin hydrochloride and linagliptin, while accounting for the existence of metformin toxic impurity 1-cyanoguanidine in their pure and dosage forms...