- |||||||||| semaglutide SC once-daily (NN9536) / Novo Nordisk
PK/PD data, Journal: Brain uptake pharmacokinetics of incretin receptor agonists showing promise as Alzheimer's and Parkinson's disease therapeutics. (Pubmed Central) - Jan 1, 2021
Of the non-acylated, non-PEGylated IRAs tested, exendin-4 and DA-JC4 were best able to cross the BBB based on their rate of brain influx, percentage reaching the brain that accumulated in brain parenchyma, and percentage of the systemic dose taken up per gram of brain tissue. Exendin-4 and DA-JC4 thus merit special attention as IRAs well-suited to enter the central nervous system (CNS), thus reaching areas pathologic in AD and PD.
- |||||||||| Lantus (insulin glargine) / Sanofi
Clinical, Journal: Management of the T2D Patient With High A1C. (Pubmed Central) - Dec 20, 2020
The speakers discuss the positive outcomes associated with a shorter interval between diagnosis and intensive insulin treatment, and the benefits of timely treatment intensification. They also provide practical advice for counseling patients to achieve an effective transition to injectable medication.
- |||||||||| semaglutide SC once-daily (NN9536) / Novo Nordisk
Review, Journal: An overview of GLP-1 agonists and recent cardiovascular outcomes trials. (Pubmed Central) - Dec 18, 2020
These findings have transformed our guidelines on pharmacological treatment of T2D. This review article will discuss GLP-1 RA therapy, review the seven CVOTs reported to date and discuss the implications on current guidelines and therapies going forward.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Preclinical, Journal: Low-dose lixisenatide protects against early-onset nephropathy induced in diabetic rats. (Pubmed Central) - Dec 18, 2020
This review article will discuss GLP-1 RA therapy, review the seven CVOTs reported to date and discuss the implications on current guidelines and therapies going forward. Low-dose lixisenatide treatment was able to protect against early diabetic nephropathy, which might represent a promising approach in the management of diabetes and its renal complication however, further clinical studies are warranted.
- |||||||||| Review, Journal: Anti-inflammatory properties of antidiabetic drugs: A "promised land" in the COVID-19 era? (Pubmed Central) - Dec 16, 2020
Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs (i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: Identification of Theaflavin-3,3'-Digallate as a Novel Zika Virus Protease Inhibitor. (Pubmed Central) - Nov 18, 2020
Moreover, ZP10 was showed to directly bind to ZIKVpro, and a docking model further revealed that ZP10 interacted with several critical residues at the proteolytic cavity of the ZIKVpro. This study highlights that ZP10 has anti-ZIKV potency through ZIKVpro inhibition, which indicates its potential application in anti-ZIKV therapy.
- |||||||||| Byetta (exenatide) / AstraZeneca, semaglutide SC once-daily (NN9536) / Novo Nordisk
Retrospective data, Journal: GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: an updated meta-analysis including the REWIND and PIONEER 6 trials. (Pubmed Central) - Sep 30, 2020
GLP-1RA also reduced the risk cardiovascular death by 12%, nonfatal stroke by 16%, hospitalisation for heart failure by 9%, all-cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven by a reduction in macroalbuminuria only (HR = 0.76, 0.68-0.86, P = 0.003). GLP-1RA have moderate benefits on MACE, and also reduce hospitalisation for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease.
- |||||||||| Review, Journal: Type 2 diabetes and the kidney: insights from cardiovascular outcome trials. (Pubmed Central) - Sep 19, 2020
Despite some residual limitations linked to differences in study populations and patient characteristics, the cardiorenal protective actions of SGLT-2 inhibitors, and to a lesser extent by some GLP-1 agonists, make them favorable medications for patients with T2D at increased cardiorenal risk. There is room for optimism that their use may change the paradigm of the ineluctable progression of DKD.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi, doxorubicin hydrochloride / Generic mfg.
Journal: Lixisenatide protects doxorubicin-induced renal fibrosis by activating wNF-κB/TNF-α and TGF-β/Smad pathways. (Pubmed Central) - Sep 9, 2020
These results suggest that iGlarLixi achieves superior glycaemic control compared with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or those inadequately controlled on two OADs. Lixisenatide protects doxorubicin-induced renal fibrosis in rats by inhibiting NF-κB/TNF-α and TGF-β/Smad pathways.
- |||||||||| Byetta (exenatide) / AstraZeneca
Review, Journal: An overview of glucagon-like peptide-1 receptor agonists for the treatment of metabolic syndrome: A drug repositioning. (Pubmed Central) - Aug 4, 2020
Some these effects are related to a reduction in food-seeking behavior, an increase in atrial natriuretic peptide level and hence vascular relaxation and natriuresis, and an increase of pancreas β-cell mass and protection against glucotoxicity. Collectively, this review indicates that there may be some value in GLP-1RAs repositioning to manage MetS risk factors beyond their anti-diabetic effects.
- |||||||||| Onglyza (saxagliptin) / AstraZeneca, Byetta (exenatide) / AstraZeneca
[VIRTUAL] Effects of incretin-based drugs and irisin in pancreatic beta cells treated with pasireotide (Poster Hall) - Jul 2, 2020 - Abstract #EASD2020EASD_206;
Both incretin-based drugs and irisin are able to reduce the proapoptotic effects of pasireotide, acting through partly different mechanisms. These results demonstrate for the first time a functional antagonism between SSTR2/5 activation and incretin-based drugs/irisin in pancreatic beta-cells.
- |||||||||| Byetta (exenatide) / AstraZeneca
Clinical, Retrospective data, Journal, HEOR, Real-World Evidence: Glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: real-world evidence from a Mediterranean area. (Pubmed Central) - Jun 19, 2020
In this real-world, retrospective study, the magnitude of HbA1c and body weight reductions after addition of a GLP-1RA were similar to those observed in randomized controlled trials. Approximately sixty percent of patients attained reductions in both HbA1c and body weight, and there were significant differences among different drugs from this therapeutic group.
- |||||||||| semaglutide SC once-daily (NN9536) / Novo Nordisk
Review, Journal: GLP-1 Receptor Agonists and Cardiovascular Outcome Trials: An Update. (Pubmed Central) - Jun 5, 2020
Thus, it is conceivable that there are different drug-specific properties across the class of GLP-1 RAs. In this review, we discuss the results of the five recently published randomised CV outcome trials with GLP-1 RAs, along with the potential differences and the pleiotropic actions of these agents on the CV system.
- |||||||||| Byetta (exenatide) / AstraZeneca
Clinical, Review, Journal: The use of GLP-1 receptor agonists in hospitalised patients: an untapped potential. (Pubmed Central) - Jun 5, 2020
Pilot studies were reported in the fields of acute stroke, cardiac resuscitation, coronary care and perioperative care that showed advantages for GLP-1 therapy; with normalisation of glucose, lower glucose variability and lower risk of hypoglycaemia. Animal and human studies have reported improvements in myocardial performance when given acutely after vascular insult or surgery, but these have yet to be translated into randomised clinical trials.
- |||||||||| Soliqua 100/33 (lixisenatide + insulin glargine) / Sanofi, Lantus (insulin glargine) / Sanofi, Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Clinical, Journal: Clinical Characteristics and Glycemic Outcomes of Patients with Type 2 Diabetes Requiring Maximum Dose Insulin Glargine/Lixisenatide Fixed-Ratio Combination or Insulin Glargine in the LixiLan-L Trial. (Pubmed Central) - May 29, 2020
P3
Maximum doses of iGlarLixi were required in participants with a more insulin-resistant clinical phenotype (younger, higher BMI, FPG, and insulin doses). Benefits were observed with iGlarLixi vs. iGlar, even at 60 units/day, with more participants achieving glycemic goals, no increase in symptomatic hypoglycemia, and a modest reduction in body weight.
- |||||||||| Byetta (exenatide) / AstraZeneca, semaglutide SC once-daily (NN9536) / Novo Nordisk
Retrospective data, Review, Journal: Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. (Pubmed Central) - May 27, 2020
Benefits were observed with iGlarLixi vs. iGlar, even at 60 units/day, with more participants achieving glycemic goals, no increase in symptomatic hypoglycemia, and a modest reduction in body weight. Treatment with GLP-1 receptor agonists has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes.
- |||||||||| Onglyza (saxagliptin) / AstraZeneca, Byetta (exenatide) / AstraZeneca
[VIRTUAL] The Somatostatin Analog Pasireotide Reduces Pancreatic ß-Cell Function and Survival, and Both Incretin-Based Drugs and Irisin Revert These Effects () - May 18, 2020 - Abstract #ADA2020ADA_2744;
The diabetogenic effects of pasireotide are significantly reduced in vivo by the co-administration of liraglutide or vildagliptin...Pretreatment with both incretin-based drugs (exendin-4, lixisenatide, liraglutide, saxagliptin) and irisin prevented pasireotide-induced apoptosis in INS-1E cells...Both GLP-1 receptor agonists and DPP-4 inhibitors and irisin can reduce the proapoptotic effects of pasireotide, acting through partially different molecular mechanisms. These results demonstrate for the first time a functional antagonism between SSTR2/5 activation and incretin-based drugs or irisin in pancreatic β-cells.
- |||||||||| Steglatro (ertugliflozin) / Pfizer, Merck (MSD), Jardiance (empagliflozin) / Eli Lilly, Boehringer Ingelheim, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
[VIRTUAL] Coverage, Formulary Restrictions, and Average Retail Prices of SGLT2 Inhibitors and GLP-1 Receptor Agonists across Medicare Part D Plans in 2019 () - May 18, 2020 - Abstract #ADA2020ADA_1936;
The mean retail price [IQR] for a 30-day supply of a SGLT2i or a GLP-1RA ranged from $295 [$285-$303] (ertugliflozin) to $512 [$501-$527] (canagliflozin) and $641.38 [$629-$657] (lixisenatide) to $946.17 [$930-$968] (liraglutide), respectively...Most beneficiaries enrolled in plans that covered at least one SGLT2i and one GLP-1RA without restrictions. Cost sharing (i.e., high out-of-pocket payments) may be more problematic for patients than either prior authorization or step therapy.
- |||||||||| IDegLira (insulin degludec/liraglutide) / Novo Nordisk, Soliqua 100/33 (lixisenatide + insulin glargine) / Sanofi, Lantus (insulin glargine) / Sanofi
[VIRTUAL] Indirect Treatment Comparison (ITC) of IGlarLixi vs. IDegLira in Adults Inadequately Controlled by GLP-1 Receptor Agonists (GLP-1RAs) () - May 18, 2020 - Abstract #ADA2020ADA_1773;
Hypoglycemia comparisons suffered from varying definitions, sulfonylurea (SU) use and eligibility, and few events in the GLP-1 RA arms (incidence: 32% [confirmed ≤3.1 mmol/L, 28% without SU] with IDegLira and 9% or 28% [symptomatic <3.0 or ≤3.9 mmol/L] with iGlarLixi). This ITC shows similar FRC HbA1c glycemic target achievement but suggests divergent differences in other glycemia results and hypoglycemia, likely due to different study design and titration application.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
[VIRTUAL] The Impact of Blood Pressure on Risk of Death Is Influenced by Prior Cardiovascular Disease in Patients with Type 2 Diabetes and a Recent Coronary Event () - May 18, 2020 - Abstract #ADA2020ADA_1315;
We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline systolic blood pressure (SBP) and mortality in 5852 patients with T2DM who, as required for entry to the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial, had a recent acute coronary syndrome (ACS)...Overall there was no significant association between SBP and risk of death (P=0.20), but in 2325 patients with additional CVD (index ACS + at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure) there was a significant association between lower SBP and higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13; 95% CI 1.05 to 1.23) whereas in 3527 patients with only the index ACS no association was observed (hazard ratio per 10 mmHg lower SBP 0.95; 95% CI 0.86 to 1.04, P for interaction <0.001). In ELIXA participants, an association between lower SBP and higher risk of death was seen only in patients with additional CVD.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
[VIRTUAL] The Impact of Blood Pressure on Risk of Death Is Influenced by Prior Cardiovascular Disease in Patients with Type 2 Diabetes and a Recent Coronary Event () - May 18, 2020 - Abstract #ADA2020ADA_1144;
We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline systolic blood pressure (SBP) and mortality in 5852 patients with T2DM who, as required for entry to the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial, had a recent acute coronary syndrome (ACS)...Overall there was no significant association between SBP and risk of death (P=0.20), but in 2325 patients with additional CVD (index ACS + at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure) there was a significant association between lower SBP and higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13; 95% CI 1.05 to 1.23) whereas in 3527 patients with only the index ACS no association was observed (hazard ratio per 10 mmHg lower SBP 0.95; 95% CI 0.86 to 1.04, P for interaction <0.001). In ELIXA participants, an association between lower SBP and higher risk of death was seen only in patients with additional CVD.
- |||||||||| Byetta (exenatide) / AstraZeneca
Review, Journal: The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes in Asia. (Pubmed Central) - May 2, 2020
A short-acting GLP-1RA plus basal insulin is an alternative to premixed insulin, resulting in better efficacy and a lower risk of hypoglycemia and weight gain. In conclusion, GLP-1RAs, especially short-acting GLP-1RAs, are a practical treatment option for East Asian patients with T2D inadequately controlled by OADs or basal insulin.Funding: Sanofi.
- |||||||||| Lyxumia (lixisenatide) / Zealand Pharma, Sanofi
Journal: Effect of Incorporating Zirconia Powder into a Primer on the Resin Bond Strength to Zirconia Ceramic. (Pubmed Central) - Apr 28, 2020
A commercial zirconia primer was modified through the addition of 0 (control), 5, 10, 25, and 50 wt% of a zirconia powder (codes: ZP0, ZP5, ZP10, ZP25, and ZP50, respectively)...The lowest SBS value was obtained for the ZP50 group. The results suggest that the incorporation of a zirconia powder into a primer represents a promising modification method for improving the resin bond strength to zirconia ceramic.
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