linagliptin / Generic mfg. 
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  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    Trial primary completion date:  Effects of DPP4 Inhibition on COVID-19 (clinicaltrials.gov) -  Sep 7, 2020   
    P4,  N=20, Not yet recruiting, 
    In patients with T2D undergoing non-cardiac surgery presenting with mild to moderate hyperglycaemia (BG <11.1 mmol/L), daily linagliptin is a safe and effective alternative to multi-dose insulin therapy resulting in similar glucose control with lower hypoglycaemia. Trial primary completion date: Dec 2020 --> Mar 2021
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, semaglutide SC once-daily (NN9536) / Novo Nordisk
    Expectations for incretin-related drugs as a new treatment strategy for DKD (Room 2 (North, 3rd floor, G303+G304)) -  Aug 30, 2020 - Abstract #JSN2020JSN_479;    
    Evaluation of diabetic kidney disease (DKD) and renal events in the LEADER study and SUSTAIN-6, which verified the safety of the GLP-1 receptor agonists Liraglutide and Semaglutide against cardiovascular events in patients with type 2 diabetes The LEADER study showed a decrease in combined renal outcomes in the Liraglutide-treated group and suppression of new onset of persistent Macroalbuminuria (NEJM 2017)...In addition, in the CARMELINA study that evaluated the cardiovascular and renal outcomes of the DPP-4 inhibitor Linagliptin in patients with type 2 diabetes mellitus at high cardiovascular and renal risk, inhibition of albuminuria progression in the Linagliptin-administered group was also shown...(3) Administration of DPP-4 inhibitors not only enhances GLP-1 receptor signaling in the kidney but also Amelioration of glomerular hypertension by increasing expression of distant nephrons of chemokine SDF-1, another target of DPP-4, and promoting Na excretion in urine through this (Kidney Int 2016), etc. Has reported new findings. In this symposium, we will outline the above.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    [VIRTUAL] Trajenta®: Simplifying the management of T2D. From CARMELINA to CAROLINA (Room 4) -  Aug 18, 2020 - Abstract #KSN2020KSN_67;    
    DPP-4 inhibitors were found to have a neutral effect on macrovascular and microvascular complications, with the exception of saxagliptin, which may increase the risk for heart failure hospitalizations. Sponsored by Yuhan Corporation
  • ||||||||||  Journal:  Contemporary Trends in Prescription of Dipeptidyl Peptidase-4 Inhibitors in the Context of US Food and Drug Administration Warnings of Heart Failure Risk. (Pubmed Central) -  Aug 13, 2020   
    The vast majority of prescriptions were sitagliptin (85.7%), followed by linagliptin (9.5%), saxagliptin (4.7%), and alogliptin (0.2%)...In conclusion, although DPP-4i remain a dominant oral antihyperglycemic therapy in clinical practice, new prescriptions have declined recently. These data may reflect relatively swift health system response to broad FDA safety communications regarding heart failure risk, which appeared to impact the entire DPP-4i class, including specific drugs that have not demonstrated any increased risk of heart failure.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    Clinical, Journal:  Effects of linagliptin on left ventricular DYsfunction in patients with type 2 DiAbetes and concentric left ventricular geometry: results of the DYDA 2 trial. (Pubmed Central) -  Jul 30, 2020   
    P3
    Together, these findings from the CARMELINA trial reaffirm treatment guidelines for choosing additional therapies for patients with T2DM at elevated CV and/or renal risk, and provide new information on the role of linagliptin in the management of T2DM. In the DYDA 2 patients the addition of linagliptin to stable diabetes therapy was safe and provided a modest non-significant increase in left ventricular systolic function measured as midwall fractional shortening.Trial registration number: ClinicalTrial.gov (ID NCT02851745).
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    Trial completion date:  Effects of DPP4 Inhibition on COVID-19 (clinicaltrials.gov) -  Jul 13, 2020   
    P4,  N=20, Not yet recruiting, 
    In the DYDA 2 patients the addition of linagliptin to stable diabetes therapy was safe and provided a modest non-significant increase in left ventricular systolic function measured as midwall fractional shortening.Trial registration number: ClinicalTrial.gov (ID NCT02851745). Trial completion date: Dec 2020 --> Mar 2021
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    [VIRTUAL] Glucagon-like peptide-2 exerts a strong anti-inflammatory response on isolated human islets (Poster Hall) -  Jul 2, 2020 - Abstract #EASD2020EASD_1250;    
    While the effect of GLP2 is modulated through GLP-2R expressed on beta-cells, the anti-inflammatory response could be rather beta-cell-indirect through infiltrating immune cells. The observed anti-inflammatory effect of GLP-2 needs to be further investigated in order to establish possible GLP-2 directed therapies for diabetes.
  • ||||||||||  Clinical, Journal:  Dipeptidyl Peptidase-4 inhibitors use in type II diabetic patients in a tertiary hospital. (Pubmed Central) -  Jun 23, 2020   
    Patients with T2DM treated with available DPP-4i; namely Linagliptin, Saxagliptin, Sitagliptin and Vildagliptin, for at least 3 months were identified from the pharmacy record...Majority of the patients (90.4%) were prescribed with Metformin, with 62.8% of patients on fixed-dose combination, and the remaining on add-on Metformin therapy...None of the ADR reported caused any significant harm to the patients. Overall, use of these DPP-4i as an adjunct antidiabetic was associated with reduction in HbA1c.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Januvia (sitagliptin) / Merck (MSD)
    [VIRTUAL] Induction of the Pro-Diabetic Gene DPP4 by Glucocorticoids: New Evidence of Pro-Inflammatory Effects in Macrophages () -  Jun 20, 2020 - Abstract #ENDOI2020ENDO-I_1946;    
    Provocatively, DPP4 has been shown to be involved in the inflammatory macrophage profile associated with type 2 diabetes, obesity and atherosclerosis. Since macrophages require efficient cell movement for all their functions, such as sensing of Pattern Associated Molecular Patterns (PAMPs), phagocytosis and the antigen presentation, the DPP4 induction by glucocorticoids could potentiate the macrophage infiltration and their activation in chronic inflammatory tissues and diabetes.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    Preclinical, Journal:  Renoprotective Effect of a Dipeptidyl Peptidase-4 Inhibitor on Aging Mice. (Pubmed Central) -  Jun 7, 2020   
    C57BL/6 mice were divided into three groups: the two-month-old mice (YM group), the eighteen-month-old mice (AM group) and the eighteen-month-old, linagliptin-treated mice (AM + LIN group)...NADPH oxidase 2 and NADPH oxidase 4 levels decreased in the AM + LIN group (p < 0.001 compared with the AM group for both proteins), whereas the levels of endothelial nitric oxide synthase (eNOS) phosphorylated at serine and superoxide dismutase 1 were increased (p < 0.01 compared with the AM group for both proteins). DPP-4 inhibitors may exert renoprotective effects via prorenin receptor/angiotensin-converting enzyme/angiotensin II/angiotensin 1 receptor axis.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    Preclinical, Journal:  The role of GIP and pancreatic GLP-1 in the glucoregulatory effect of DPP-4 inhibition in mice. (Pubmed Central) -  Jun 4, 2020   
    DPP-4 inhibitors may exert renoprotective effects via prorenin receptor/angiotensin-converting enzyme/angiotensin II/angiotensin 1 receptor axis. Taken together, these data suggest that increases in pancreatic GLP-1 and GIP are necessary for the full effect of DPP-4 inhibitors on glucose tolerance.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Synjardy (empagliflozin/metformin) / Boehringer Ingelheim, Eli Lilly, Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim
    Trial completion date, Trial primary completion date, Real-world evidence, Real-world:  DIA_CENTRAL:T2D Treatment Pattern in Central Europe (clinicaltrials.gov) -  May 28, 2020   
    P=N/A,  N=4000, Active, not recruiting, 
    2019; XX:XXX-XXX) Trial completion date: May 2020 --> Jan 2021 | Trial primary completion date: May 2020 --> Jan 2021
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    Preclinical, Journal:  High dose of linagliptin induces thermogenic beige adipocytes in the subcutaneous white adipose tissue in diet-induced obese C57BL/6 mice. (Pubmed Central) -  May 27, 2020   
    Trial completion date: May 2020 --> Jan 2021 | Trial primary completion date: May 2020 --> Jan 2021 The reduced BM, the enhanced body temperature, and the presence of positive UCP1 beige cells in the sWAT point to the activation of the browning cascade on the sWAT of linagliptin-treated mice, and hence, linagliptin could induce the thermogenic pathway as a pleiotropic effect that can have translational potential.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, glimepiride / Generic mfg.
    [VIRTUAL] Interrelationship between Hypoglycemia (HYPO) and Cardiovascular (CV) and Mortality Outcomes in the CAROLINA Trial () -  May 18, 2020 - Abstract #ADA2020ADA_3428;    
    Of note, even when multivariably adjusted, occurrence of HYPO was associated only with higher risk for all-cause mortality (HR 1.49 [1.16, 1.92]), and non-CV mortality (HR 2.16 [1.57, 2.97]) (Fig A). The relative effect of LINA vs. GLIM on any CV or mortality outcome (Fig B) was not influenced by antecedent HYPO.In conclusion, preceding HYPO was associated with higher risk for all-cause and non-CV mortality, but not with any other outcomes in a relatively early T2D population at elevated CV risk.
  • ||||||||||  metformin / Generic mfg., Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
    [VIRTUAL] Linagliptin Improves CD34+ Progenitor Cells and Urine Exosomes () -  May 18, 2020 - Abstract #ADA2020ADA_2991;    
    Cellular mechanisms of DPP-4 inhibitors such as Linagliptin (LG) on CVD risk in patients with type 2 diabetes with established CKD has not been established.Hypothesis: Linagliptin, a DPP-4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD) 31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, glimepiride / Generic mfg.
    [VIRTUAL] Cardiovascular (CV) and Hypoglycemia Outcomes across Age Groups in People with Type 2 Diabetes (T2D) in the CAROLINA Trial () -  May 18, 2020 - Abstract #ADA2020ADA_2863;    
    Over time, following some initial dynamics, changes in HbA1c levels were comparable between treatment-groups and across age, but hypoglycemia risk (Fig) and weight were significantly lower with LINA vs. GLIM overall and consistently across age groups. These data demonstrate that results for CV and mortality outcomes were consistent across age subgroups, but LINA has a modest benefit in weight and a significantly lower hypoglycemia burden than GLIM, which are important safety considerations when selecting therapy for the elderly.
  • ||||||||||  [VIRTUAL] Linagliptin Directly Enhances Cardiac Contractile Recovery through Nitric Oxide Mediated Endothelial–Cardiomyocyte Communication () -  May 18, 2020 - Abstract #ADA2020ADA_2283;    
    Thus, at concentrations achieved with standard dosing in humans, linagliptin has direct effects on the recovery of mouse cardiac contractility after ischemia-reperfusion, most likely through NO-mediated endothelial-cardiomyocyte communication. The complex cardiac actions of NO (that depend on comorbidity, concurrent medications and disease setting, for instance) may contribute to both the discordance in DPP-4 inhibitor outcomes between preclinical and clinical observations and the heterogeneous outcomes observed in clinical trials to date.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, glimepiride / Generic mfg.
    [VIRTUAL] Validation of a New Diabetes Staging System (DSS) for Type 2 Diabetes (T2D) Using Data from Three Cardiovascular Outcomes Trials (CVOTs) () -  May 18, 2020 - Abstract #ADA2020ADA_1995;    
    By use of investigator reported baseline conditions, we categorized patients into DSS stages and calculated incidence rates (IR) for all-cause death.We observed a pattern of increasing IR for death with more advanced DSS stage, although with overlapping confidence intervals, with some variations between trials (Figure). A pattern of eGFR<60 ml/min/1.73m2 impacting in more advanced stages were observed across trials, whereas the pattern for HbA1c was less clear.Higher DSS stage appeared to be associated with increased mortality across all three CVOT trials but needs validation in the general T2D populations.
  • ||||||||||  Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, glimepiride / Generic mfg.
    [VIRTUAL] Incident and Recurrent Hypoglycemia with Linagliptin and Glimepiride in the CAROLINA Trial () -  May 18, 2020 - Abstract #ADA2020ADA_1767;    
    HbA1c over time did not differ between groups, but a significantly lower frequency of HYPO events was observed with LINA (Fig), regardless of definition, a difference further accentuated when including recurrent HYPO.In conclusion, these data demonstrate that LINA, compared with GLIM, has a significantly lower HYPO burden. Given the potentially harmful clinical impact of HYPO, these data may help inform therapy selection.