- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Preclinical, Journal: The Dipeptidyl Peptidase-4 Inhibitor Linagliptin Ameliorates High-fat Induced Cognitive Decline in Tauopathy Model Mice. (Pubmed Central) - Nov 23, 2019
Linagliptin treatment significantly restored spatial reference memory and increased cerebral blood flow without affecting phosphorylation levels of tau or endothelial nitric oxide synthase (eNOS) in the brain. Linagliptin may ameliorate HFD-induced cognitive worsening in tauopathy, at least partially, by increasing cerebral perfusion via the eNOS-independent pathway.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Journal: CARMELINA: an important piece of the DPP-4 inhibitor CVOT puzzle. (Pubmed Central) - Nov 14, 2019
With the recent disclosure of data from the CARMELINA cardiovascular outcomes trial (CVOT), which investigated linagliptin, CV and renal outcomes data are now available for four agents in the DPP-4 inhibitor class that are approved in most markets...Given the risk for future development of renal impairment that is associated with T2D even in patients without current overt CKD, we believe that the CARMELINA study provides important new insights that are clinically relevant for a broad range of patients. Finally, we discuss how these insights can be integrated into the approach to the pharmacotherapeutic management of hyperglycaemia that is recommended in newly updated guidelines.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Journal, IO Biomarker: Linagliptin Inhibits Lipopolysaccharide-Induced Inflammation Concentration-Dependently And -Independently. (Pubmed Central) - Nov 7, 2019
Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment in the context of LPS-induced pro-inflammatory responses. Thus, our findings suggested that linagliptin induced two different mechanisms to repress inflammation, i.e., TLR4-dependent and -independent mechanisms.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Clinical, Journal: Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA. (Pubmed Central) - Oct 29, 2019
P4
Thus, our findings suggested that linagliptin induced two different mechanisms to repress inflammation, i.e., TLR4-dependent and -independent mechanisms. In a large, international cardiovascular outcome trial in participants with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease, linagliptin did not affect the risk of hHF or other selected HF-related outcomes, including among participants with and without a history of HF, across the spectrum of kidney disease, and independent of previous left ventricular ejection fraction.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Aimovig (erenumab) / Amgen, Novartis
Improvement in Cervical Radiculopathy by Erenumab During the Preventive Treatment of Migraine in a Patient with CKD () - Oct 23, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_5895;
She was taking pantoprazole, sacubitril/valsartan, metoprolol, clonidine, aspirin, linagliptin, pravastatin, alirocumab, denosumab, gabapentin, pentoxifylline, calcitriol, erythropoietin, sevelamer and pain medications including narcotics...This incidental finding may suggest additional use of CGRP-inhibitor for the treatment of radiculopathy. Therefore, further researches are necessary to prove this hypothesis.
- |||||||||| Journal: Risk of Hypoglycemia After Concomitant Use of Antidiabetic, Antihypertensive, and Antihyperlipidemic Medications: A Database Study. (Pubmed Central) - Oct 12, 2019
The concomitant use of sitagliptin/buformin, exenatide/voglibose, repaglinide/barnidipine, teneligliptin/barnidipine, teneligliptin/urapidil, exenatide/candesartan, voglibose/barnidipine, voglibose/guanabenz, or exenatide/tocopherol was detected in both the JADER and Food and Drug Administration Adverse Event Reporting System databases. Combination therapy with the drugs listed above would show potential interactions that could result in hypoglycemia in patients with diabetes mellitus.
- |||||||||| Journal: Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent. (Pubmed Central) - Oct 11, 2019
Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition...LC-MS/MS determination of once-weekly anti-diabetic DPP-4 inhibitors; omarigliptin & trelagliptin in plasma and brain tissue was employed after 2 h of oral administration to rats...A novel intranasal formulation was developed using sodium lauryl sulphate surfactant to solubilize the lipophilic omarigliptin with penetration enhancing & antimicrobial properties. Intranasal administration showed enhanced brain/plasma ratio by 3.3 folds compared to the oral group accompanied with 2.6 folds increase in brain glucagon-like peptide-1 concentration compared to the control group.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Journal: Linagliptin-Associated Alopecia and Bullous Pemphigoid. (Pubmed Central) - Oct 5, 2019
To the best of our knowledge, this is the first report of linagliptin-associated alopecia areata and bullous pemphigoid, which may help demonstrate if there are any links between DPP-4 inhibitors and alopecia. This is the first report of linagliptin-associated alopecia areata and bullous pemphigoid (BP), which may help demonstrate a link between DPP-4 inhibitors and alopecia.Since the time of onset of BP after initiation of a DPP-4 inhibitor varies, a high index of suspicion is needed for diagnosis.Early diagnosis is essential as DPP-4 inhibitor withdrawal has a significant effect on disease remission.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Jentadueto (linagliptin+metformin) / Eli Lilly, Boehringer Ingelheim
Clinical, Journal, Combination therapy, Monotherapy: Which is better, high-dose metformin monotherapy or low-dose metformin/ linagliptin combination therapy, in improving glycemic variability in type 2 diabetes patients with insufficient glycemic control despite low-dose metformin monotherapy: A randomized, crossover, CGM-based, pilot study. (Pubmed Central) - Oct 2, 2019
Discontinuation of DPP-4 inhibitor treatment in patients with diabetes should be considered when BP is diagnosed. A comparison of GV with HMET versus LMET + DPP4 suggested that LMET + DPP4 might reduce post-breakfast GV to a greater degree than HMET in type 2 diabetes patients receiving low-dose metformin monotherapy.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Enrollment change, Trial completion date, Trial initiation date, Trial primary completion date: Efficacy and Safety of Lima Association in the Control of Type II Diabetes Mellitus. (clinicaltrials.gov) - Sep 30, 2019
P3, N=660, Not yet recruiting,
A comparison of GV with HMET versus LMET + DPP4 suggested that LMET + DPP4 might reduce post-breakfast GV to a greater degree than HMET in type 2 diabetes patients receiving low-dose metformin monotherapy. N=480 --> 660 | Trial completion date: Oct 2020 --> Nov 2022 | Initiation date: Jun 2019 --> Dec 2020 | Trial primary completion date: Jun 2020 --> Oct 2022
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Clinical, Journal: The MARLINA-T2D trial: putting the results into clinical perspective. (Pubmed Central) - Sep 26, 2019
Although there was no conclusive evidence of renoprotective effects, previous research suggests that clinically apparent renal benefits might develop with longer term treatment. The results of ongoing trials with primary renal endpoints are awaited with interest.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Sugarnon (evogliptin) - Dong / A
Trial completion, Trial completion date, Trial primary completion date, Head-to-Head: DA1229: Effect of Evogliptin on Albuminuria in Patients With Type 2 Diabetes and Renal Insufficiency (clinicaltrials.gov) - Sep 22, 2019
P2, N=209, Completed,
The results of ongoing trials with primary renal endpoints are awaited with interest. Enrolling by invitation --> Completed | Trial completion date: Jan 2019 --> May 2019 | Trial primary completion date: Nov 2018 --> May 2019
- |||||||||| Review, Journal: Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors. (Pubmed Central) - Sep 20, 2019
Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors...However, subsequent CV outcome trials with alogliptin, saxagliptin, and sitagliptin showed noninferiority but failed to demonstrate any superiority compared with placebo in patients with type 2 diabetes mellitus and high CV risk...CVD-REAL studies (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors; with the limitation of an observational approach) suggested that these favorable results may be considered as a class effect shared by all SGLT-2 inhibitors (including dapagliflozin) and be extrapolated to a larger population of patients with type 2 diabetes mellitus in primary prevention. Ongoing CV outcome trials with other DPP-4 (linagliptin) and SGLT-2 (dapagliflozin, ertugliflozin) inhibitors should provide additional information about CV effects of both pharmacological classes.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Synjardy (empagliflozin/metformin) / Boehringer Ingelheim, Eli Lilly, Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim
Enrollment closed, Real-world evidence, Real-world: DIA_CENTRAL:T2D Treatment Pattern in Central Europe (clinicaltrials.gov) - Sep 18, 2019
P=N/A, N=4000, Active, not recruiting,
Ongoing CV outcome trials with other DPP-4 (linagliptin) and SGLT-2 (dapagliflozin, ertugliflozin) inhibitors should provide additional information about CV effects of both pharmacological classes. Not yet recruiting --> Active, not recruiting
- |||||||||| Review, Journal: Cardiovascular effects of sitagliptin --an anti-diabetes medicine. (Pubmed Central) - Sep 18, 2019
These effects are mainly conducted through DPP-4 inhibitions. In addition, sitagliptin exerts anti-inflammation, anti-oxidative stress, anti-apoptosis, mediation on lipid accumulation and so on, which also contributing to its cardiovascular effects.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly, Onglyza (saxagliptin) / AstraZeneca, Januvia (sitagliptin) / Merck (MSD)
Clinical, Journal: Concordance with prescribing information dosage recommendations for dipeptidyl-peptidase-4 inhibitors among type 2 diabetes mellitus patients with moderate to severe chronic kidney disease. (Pubmed Central) - Sep 12, 2019
In addition, sitagliptin exerts anti-inflammation, anti-oxidative stress, anti-apoptosis, mediation on lipid accumulation and so on, which also contributing to its cardiovascular effects. More than a third of DPP4-i patients with CKD stage 3b or higher were prescribed doses not concordant with DPP4-i label dosage recommendations.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Trial completion: VCG4: Contrast Nephropathy in Type 2 Diabetes (clinicaltrials.gov) - Sep 9, 2019
P=N/A, N=40, Completed,
Linagliptin is superior to glimepiride in regard to the preservation of endothelium-dependent relaxation in the presence of hyperglycemia and the improvement in endothelial function in response to linagliptin treatment is associated with greater antioxidant activity compared to glimepiride. Recruiting --> Completed
- |||||||||| Clinical, Review, Journal: Management of diabetes mellitus in patients undergoing liver transplantation. (Pubmed Central) - Aug 25, 2019
Special issues in the management of post-transplant diabetes include the diabetogenic potential of immunosuppressant drugs and the increased cardiovascular risk characterizing solid organ transplant survivors. Overall, the pharmacological management of cirrhotic patients undergoing liver transplantation is complicated by the lack of specific guidelines reflecting the paucity of data on the impact of glycaemic control and the safety and efficacy of anti-hyperglycaemic agents in these individuals.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Cardiac Dysfunction Induced by Incretin-Related Drugs Due to Energetic Starvation in Non-Diabetic Failing Heart (Zone 1, Science and Technology Hall) - Aug 21, 2019 - Abstract #AHA2019AHA_6390;
Extra higher glucose-demand arose and cardiac function was exacerbated by treatment with incretin-related drug in failing heart, which was caused as the result that energy, especially glucose, could not meet the augmented carbohydrate demand by incretin-related drugs. Incretin-related treatment with an appropriate glycemic balance as energy regulation should be required when applying GLP-1 analogue to the patients with heart failure.
- |||||||||| Review, Journal: Cardiovascular protection in type 2 diabetes: insights from recent outcome trials. (Pubmed Central) - Aug 21, 2019
...Some studies on glucagon-like peptide-1 receptor agonists (liraglutide: LEADER trial; semaglutide: SUSTAIN-6 trial) found significant benefits for MACE, while treatment with sodium-glucose co-transporter-2 inhibitors (empagliflozin: EMPA-REG OUTCOME trial; canagliflozin: CANVAS trial) also significantly reduced MACE and reduced hospitalization for heart failure...This contrasts with the overall type 2 diabetes population receiving glucose-lowering therapies, where the majority of patients will not have had a MACE and will be regarded as primary prevention. Overall, the trials provide reassuring evidence that new glucose-lowering medications do not adversely affect CV events and some of these agents may offer CV protection.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
Journal: Effect of Linagliptin on Incretin-axis and Glycaemic Variability in T1DM. (Pubmed Central) - Aug 16, 2019
The increase in AUC GLP1 (Area under curve for GLP1) and decrease in AUC glucagon (Area under curve for glucagon) during the MMT in linagliptin group were also statistically insignificant. Linagliptin is not effective in reducing HbA1C and glycaemic variability in relatively well controlled T1DM patients.
- |||||||||| Tradjenta (linagliptin) / Boehringer Ingelheim, Eli Lilly
CARMELINA (Auditorium) - Aug 15, 2019 - Abstract #IDF2019IDF_143;
The CARMELINA study was a large multi-centre placebo-controlled trial to explore the cardiac and renal effects as well as mortality of the DPP-4 inhibitor, linagliptin in almost 7000 type 2 diabetic subjects at high risk of cardiovascular and renal events...There was also a modest reduction in albuminuria with DPP-4 therapy. In summary, the CARMELINA study demonstrated safety in a type 2 diabetic population at high risk of cardiovascular and renal disease.
- |||||||||| linagliptin / Generic mfg.
Enrollment closed: Linagliptin's Effect on CD34+ Stem Cells (clinicaltrials.gov) - Jul 30, 2019
P4, N=31, Active, not recruiting,
Trial primary completion date: Jul 2019 --> Jul 2020 Recruiting --> Active, not recruiting
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