- |||||||||| 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_1741;
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.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, glimepiride / Generic mfg.
[VIRTUAL] Analyses of First Plus Recurrent Cardiovascular (CV) and Hospitalization Events in the CAROLINA Trial () - May 18, 2020 - Abstract #ADA2020ADA_1041;
Analyses of first-event and first plus recurrent events are presented (Fig).In conclusion, no significant differences were observed between LINA or GLIM for either first or recurrent CV or hospitalization events. These data underscore the significant CV disease burden experienced even in relatively early T2D and reinforce the safety of LINA.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Trial completion date, Trial primary completion date: Effects of DPP4 Inhibition on COVID-19 (clinicaltrials.gov) - May 14, 2020
P4, N=20, Not yet recruiting,
These data underscore the significant CV disease burden experienced even in relatively early T2D and reinforce the safety of LINA. Trial completion date: Sep 2020 --> Dec 2020 | Trial primary completion date: Jun 2020 --> Oct 2020
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Onglyza (saxagliptin) / AstraZeneca, Januvia (sitagliptin) / Merck (MSD)
Preclinical, Journal: Reno-protective effect of linagliptin against gentamycin nephrotoxicity in rats. (Pubmed Central) - Apr 28, 2020
Linagliptin may have a beneficial effect on diabetes-related dementia by inhibiting oxidative stress and microglial activation, independently of glucose-lowering. Linagliptin may serve as a beneficial adjutant to reduce gentamycin-induced renal injury.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Januvia (sitagliptin) / Merck (MSD)
Induction of the Pro-Diabetic Gene DPP4 by Glucocorticoids: New Evidence of Pro-Inflammatory Effects in Macrophages (ENDOExpo, Booth 2114) - Apr 1, 2020 - Abstract #ENDO2020ENDO_4076;
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.
- |||||||||| Review, Journal: Heart failure and type 2 diabetes: From CVOTs, with hope. (Pubmed Central) - Mar 31, 2020
The three trials with sodium glucose co-transporter-2 inhibitors (SGLT-2i) (EMPA-REG OUTCOME with empagliflozin, CANVAS with canagliflozin and DECLARE with dapagliflozin) all revealed a robust and significant reduction in the hazard ratios of hospitalization for HF, from 27% to 35%, which remained consistent, significant and of similar magnitude regardless of the presence of a history of HF or established atherosclerotic cardiovascular disease...At present, the robust, consistent and reproducible reduction of about 30% risk of HF by SGLT-2i may be considered a class effect. The beneficial effect on MACE outcome observed with the use of some GLP-1RAs and SGLT-2i must be interpreted within the frame of the single trial.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
DPP4 inhibitor Linagliptin Accelerates Resolution Of Crescent Formation in a Rat Model of Anti-Gbm Glomerulonephritis (poster area 8) - Mar 22, 2020 - Abstract #DDG2020DDG_509;
Linagliptin showed cardiovascular and renal safety in Asian patients with T2DM and established CVD with albuminuria and/or kidney disease. In a short-term experiment (2weeks) linagliptin treatment was started either on day0 or on day7; in a long-term (8weeks) linagliptin treatment was started either preventive or on week4.In both experiments we included an untreated healthy and anti-GBM nephritic group.Kidney function, morphologic changes, DPP4-expression / -activity and mRNA expression were monitored .
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Journal, IO Biomarker: Repositioning of Hypoglycemic Drug Linagliptin for Cancer Treatment. (Pubmed Central) - Mar 21, 2020
Hypoglycemic drug linagliptin could potentially lead to novel therapeutics for the treatment of tumors, especially for colorectal cancer. Gene regulatory network is a valuable method for predicting and explaining the mechanism of drugs action.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Januvia (sitagliptin) / Merck (MSD)
Journal: Dipeptidyl peptidase-4 inhibitors can inhibit angiotensin converting enzyme. (Pubmed Central) - Mar 8, 2020
It seems that some DPP-4 inhibitors could inhibit ACE and partially explain the cardio-renal effects of these drugs. Further studies are required to determine if such inhibition could take place in the clinical settings.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Byetta (exenatide) / AstraZeneca, Januvia (sitagliptin) / Merck (MSD)
[VIRTUAL] ASSESSING ASYMMETRICAL PRESCRIBING OF ANTIDIABETIC DRUGS RELATIVE TO DIAGNOSIS OF NAFLD () - Mar 8, 2020 - Abstract #ISPOR2020ISPOR_1769;
CONCLUSIONS : The preliminary findings from this study suggest that patients are more likely to initiate these GLP-1RAs, DPP-4is, and TZDs after a NAFLD diagnosis. Further analysis will aim to establish the direct effect of a NAFLD diagnosis on the initiation of these drugs.
- |||||||||| Enrollment closed, Trial completion date, Trial primary completion date, Bariatric surgery: Roux-en-Y Gastric Bypass for BMI 27-32 Type 2 Diabetes Versus Best Medical Treatment (clinicaltrials.gov) - Mar 3, 2020
P4, N=40, Active, not recruiting,
Further analysis will aim to establish the direct effect of a NAFLD diagnosis on the initiation of these drugs. Recruiting --> Active, not recruiting | Trial completion date: Mar 2020 --> Dec 2020 | Trial primary completion date: Mar 2020 --> Dec 2020
- |||||||||| metformin / Generic mfg., Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, glimepiride / Generic mfg.
Review, Journal: The right place for Sulphonylureas today: Part of review the series: Implications of recent CVOTs in Type 2 Diabetes Mellitus. (Pubmed Central) - Mar 2, 2020
The CAROLINA trial is reassuring in demonstrating cardiovascular safety for the Sulphonylurea Glimepiride when compared directly with the DPP-4 inhibitor Linagliptin, suggesting either of these agents would be relatively safe second line options after Metformin in the majority of patients. This review provides a balanced assessment of available Sulphonylurea treatments in the context of current cardiovascular outcome trial data (CVOT) data and hopefully assists informed decision making about the place of these drugs in contemporary glucose lowering practice.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Rituxan (rituximab) / Roche, Biogen, Zenyaku Kogyo
Journal: Linagliptin-associated bullous pemphigoid treated with rituximab. (Pubmed Central) - Mar 2, 2020
There has been reported in a few case reports of increasing association between DPP-4 inhibitor use and bullous pemphigoid (BP). We report a case of association between linagliptin use and BP and subsequent treatment with rituximab.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Journal, IO Biomarker: Linagliptin protects human chondrogenic ATDC5 cells against advanced glycation end products (AGEs)-induced apoptosis via a mitochondria-dependent pathway. (Pubmed Central) - Feb 23, 2020
Moreover, Linagliptin inhibited the AGEs-induced increased ratio of Bax to Bcl-2, translocation of cytochrome C from mitochondria to the cytoplasm, and release of cleaved caspase-3. Collectively, our data indicate that the anti-diabetes drug Linagliptin has a new role in rescuing chondrocyte from insult by AGEs, and may, therefore, have the potential to treat joint disorders.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, glimepiride / Generic mfg.
Biomarker, Journal: Oxidative stress and endothelial dysfunction are associated with reduced cognition in type 2 diabetes. (Pubmed Central) - Feb 22, 2020
No significant associations were observed between biomarkers of inflammation and cognition. Elevated biomarkers of oxidation and endothelial function are associated and may play a role in reduced psychomotor speed, mental flexibility and attention in type 2 diabetes.
- |||||||||| daunorubicin / Generic mfg., Hikma, Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Neulasta (pegfilgrastim) / Amgen, Kyowa Hakko Kirin, Roche
Journal: Pegfilgrastim and linagliptin potentiate chemoattraction of Ccr2 and Cd44 stem cells accompanied by alterations of cardiac Hgf, Igf-1 and Mcp-1 in daunorubicin cardiomyopathy. (Pubmed Central) - Feb 21, 2020
Elevated biomarkers of oxidation and endothelial function are associated and may play a role in reduced psychomotor speed, mental flexibility and attention in type 2 diabetes. Although PFIL + LINA failed in universal potentiation of stem cells migration and homing, the expression of stem cell markers Ccr2 and Cd44 in the heart potentially increased through the preservation of Hgf, Igf-1 and upregulation of Mcp-1.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Clinical, P4 data, Journal: Preferential prescribing of linagliptin in type 2 diabetes patients in an expanded post-marketing surveillance study in Japan. (Pubmed Central) - Feb 14, 2020
Although such preferential prescribing might be expected, as linagliptin requires no dose adjustment or monitoring in renally or hepatically impaired patients, this innovative post-marketing surveillance approach generated important evidence that could only be shown in such a non-randomized comparative study. These data generated insights important for the design and interpretation of observational studies and spontaneous reports, which are key for public health.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Byetta (exenatide) / AstraZeneca
Journal: DPP-4 inhibition by linagliptin prevents cardiac dysfunction and inflammation by targeting the Nlrp3/ASC inflammasome. (Pubmed Central) - Feb 14, 2020
Lina and EX had similar effects on IS and post-infarction function, but Lina attenuated the activation of the inflammasome and the upregulation of collagen-1 and collagen-3 more than direct GLP-1 receptor activation. This effect depends on p38 activation with downstream upregulation of miR-146b levels that suppresses TLR4 expression.
- |||||||||| Nesina (alogliptin) / Takeda, Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Onglyza (saxagliptin) / AstraZeneca
Journal: Application and impact of run-in studies. (Pubmed Central) - Feb 7, 2020
Trials with run-in phases provided similar estimates for medication efficacy and safety compared to trials without run-in phases. Because run-in phases are costly and time-consuming, these results call their utility into question for clinical trials of short duration.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Journal: Linagliptin plus insulin for hyperglycemia immediately after renal transplantation: A comparative study. (Pubmed Central) - Feb 7, 2020
These animal data need to be confirmed in a clinical setting to determine whether linagliptin dosing should be adjusted when given concomitantly with these phytochemicals or gallic acid/ellagic acid-containing dietary supplements. The combination of linagliptin + insulin provided better glycemic control with a lower insulin dose and less severe hypoglycemia in comparison to insulin alone in patients with hyperglycemia immediately after renal transplantation.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Januvia (sitagliptin) / Merck (MSD)
Induction of the Pro-Diabetic Gene DPP4 by Glucocorticoids: New Evidence of Pro-Inflammatory Effects in Macrophages (ENDOExpo) - Feb 7, 2020 - Abstract #ENDO2020ENDO_2551;
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.
- |||||||||| linagliptin / Generic mfg.
Trial completion: Linagliptin's Effect on CD34+ Stem Cells (clinicaltrials.gov) - Feb 5, 2020
P4, N=31, Completed,
We are currently analyzing urinary exosome based data to enquire further into renal function Conclusions : In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in arterial stiffness and LDL parameters within 12 weeks of intervention. Active, not recruiting --> Completed
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Onglyza (saxagliptin) / AstraZeneca, Januvia (sitagliptin) / Merck (MSD)
Preclinical, Journal: Reno-protective effect of linagliptin against gentamycin nephrotoxicity in rats. (Pubmed Central) - Feb 1, 2020
Active, not recruiting --> Completed Linagliptin may serve as a beneficial adjutant to reduce gentamycin-induced renal injury.
- |||||||||| metformin / Generic mfg., Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Clinical, Journal: Review of the cardiovascular safety of dipeptidyl peptidase-4 inhibitors and the clinical relevance of the CAROLINA trial. (Pubmed Central) - Jan 30, 2020
Additional treatment options for those individuals who require therapy intensification, as well as in patients with T2DM and without established CVD include DPP-4 inhibitors and SUs. Since few head-to-head trials have compared the effects of different oral glucose-lowering agents on CV outcomes in T2DM, with most CVOTs using placebo as a comparator, the CAROLINA trial will provide important information on the comparative CV safety of a commonly prescribed SU and a DPP-4 inhibitor.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, tadalafil / Generic mfg.
Clinical, PK/PD data, Journal: Pharmacokinetic interaction between linagliptin and tadalafil in healthy Egyptian males using a novel LC-MS method. (Pubmed Central) - Jan 18, 2020
Co-administration of LNG with TDL resulted in TDL longer time to reach maximum plasma concentration (T), decreased oral clearance (Cl/F) and oral volume of distribution (Vd/F), increased its maximum plasma concentration (C), area under concentration-time curve (AUC), muscle pain and QTc prolongation. LNG and TDL co-administration warrants monitoring and/or TDL dose adjustment.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Enrollment change: Replication of the CARMELINA Diabetes Trial in Healthcare Claims (clinicaltrials.gov) - Jan 2, 2020
P=N/A, N=101830, Active, not recruiting,
This study suggests that linagliptin exerts renoprotection against early features of DN in rats probably by inhibition of high glucose-induced renal tubular and glomerular injury thereby hampering KIM-1 and NGAL as well as vanin-1 associated with renal inflammation, fibrosis and oxidative stress. N=76002 --> 101830
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