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Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption
J Clin Pharmacol. 2024 Feb 16. doi: 10.1002/jcph.2413. Online ahead of print.ABSTRACTThe aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding...
Source: The Journal of Clinical Pharmacology - February 16, 2024 Category: Drugs & Pharmacology Authors: Xian Ping Guopeng Wang Dongmei Gao Source Type: research

Sodium –glucose cotransporter-2 inhibitors in heart failure patients across the range of body mass index: a systematic review and meta-analysis of randomized controlled trials
AbstractSodium –glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with heart failure, with or without diabetes. We sought to assess whether there is an interaction of these effects with body mass index (BMI). A systematic review of the MEDLINE and Scopus databases (last search: November 15t h, 2022) was performed according to the PRISMA statement. Studies eligible for this review were randomized control trials (RCTs) with patients with chronic heart failure with either preserved or reduced ejection fraction randomly assigned to SGLT2 inhibitors or placebo. Data were extracted independe ntly by two r...
Source: Internal and Emergency Medicine - February 14, 2024 Category: Emergency Medicine Source Type: research

Photoinduced selective perfluoroalkylation of terminal alkynes < em > via < /em > electron donor-acceptor complexes
Chem Commun (Camb). 2024 Feb 8. doi: 10.1039/d4cc00105b. Online ahead of print.ABSTRACTHerein, we report a photoinduced selective perfluoroalkylation of terminal alkynes driven by the noncovalent interaction between a thymol anion and fluoroalkyl iodides. By precisely tuning the reaction solvent, a wide range of 37 structurally diverse perfluoroalkylated alkynes and alkenes, including ibuprofen, empagliflozin, galactose, isoxepac and indomethacin, were obtained in up to 92% yields. Mechanistic studies reveal the formation of EDA complexes between the thymol anion and fluoroalkyl iodides. This strategy may provide an import...
Source: Chemical Communications - February 8, 2024 Category: Chemistry Authors: Xiaolin Shi Bo Yu Xin Zhou Yong Yang Source Type: research

Cardiorenal effectiveness of empagliflozin vs. glucagon-like peptide-1 receptor agonists: final-year results from the EMPRISE study
No randomized clinical trials have directly compared the cardiorenal effectiveness of empagliflozin and GLP-1RA agents with demonstrated cardioprotective effects in patients with a broad spectrum of cardiovasc... (Source: Cardiovascular Diabetology)
Source: Cardiovascular Diabetology - February 8, 2024 Category: Cardiology Authors: Phyo T. Htoo, Helen Tesfaye, Sebastian Schneeweiss, Deborah J. Wexler, Brendan M. Everett, Robert J. Glynn, Niklas Schmedt, Lisette Koeneman, Anouk D éruaz-Luyet, Julie M. Paik and Elisabetta Patorno Tags: Research Source Type: research

Rates of diabetic ketoacidosis with empagliflozin use during hospitalization for acute heart failure
Visual abstract AbstractThere is concern that sodium-glucose cotransporter-2 inhibitors during hospitalization for acute heart failure (aHF) may precipitate diabetic ketoacidosis (DKA). A retrospective study of all hospitalization encounters for aHF defined by a primary HF International Classification of Diseases (ICD)-10 code in 15 Kaiser Permanente Southern California medical cente rs hospitalized between January 1, 2021 and August 31, 2023 was performed to describe rates of DKA with empagliflozin use. DKA was defined by the presence of either a DKA ICD-10 code or ketoacidosis lab criteria (bicarbonate<18 mmol/L ...
Source: Journal of Hospital Medicine - February 2, 2024 Category: Hospital Management Authors: Cheng ‐Wei Huang, Janet S. Lee, Ming‐Sum Lee Tags: BRIEF REPORT Source Type: research

Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota
This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between ...
Source: Clinical and Experimental Pharmacology and Physiology - February 1, 2024 Category: Drugs & Pharmacology Authors: Chuxin Huang Jiali Qian Ying Liu Li Zhang Yehong Yang Source Type: research

Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis
ConclusionBased on the existing studies, we concluded that SGLT2i could increase hematocrit and hemoglobin levels in patients with T2DM, and canagliflozin 100mg had the best effect on the improvement of hematocrit, while canagliflozin 200mg had the best effect on the improvement of hemoglobin.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/#loginpage, identifier PROSPERO (CRD42023477103). (Source: Frontiers in Endocrinology)
Source: Frontiers in Endocrinology - February 1, 2024 Category: Endocrinology Source Type: research

Two-Year Therapeutic Efficacy and Safety of Initial Triple Combination of Metformin, Sitagliptin, and Empagliflozin in Drug-Na ïve Type 2 Diabetes Mellitus Patients
CONCLUSION: Initial triple combination therapy with metformin, sitagliptin, and empagliflozin led to achievement of the glycemic target goal, which was maintained for 24 months without severe hypoglycemia but with improved metabolic function and albuminuria. This combination therapy may be a good strategy for drug-naïve patients with type 2 diabetes mellitus.PMID:38273791 | DOI:10.4093/dmj.2023.0128 (Source: Diabetes and Metabolism Journal)
Source: Diabetes and Metabolism Journal - January 26, 2024 Category: Endocrinology Authors: Young-Hwan Park Minji Sohn So Yeon Lee Soo Lim Source Type: research

Patient Focus: Sodium-Glucose Cotransporter-2 Inhibitor Rates for Patients with Heart Failure in the Veterans Affairs Health System. We Need to Move the Needle! An explanation of “Uptake of Sodium-Glucose Cotransporter-2 Inhibitors in Hospitalized Patients with Heart Failure: Insights from the Veterans Affairs Healthcare System”
In this issue of the Journal of Cardiac Failure, Dr. Anubodh Varshney and colleagues explore what influences the likelihood of prescription for Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) for United States ’ military veterans hospitalized with heart failure at Veteran's Affairs hospitals. SGLT2i are a relatively new class of medications that have been proven to reduce the chances of dying or being hospitalized due to heart failure.1,2 SGLT2i include medicines like dapagliflozin, empagliflozin, canag liflozin, and ertugliflozin. (Source: Journal of Cardiac Failure)
Source: Journal of Cardiac Failure - January 26, 2024 Category: Cardiology Authors: Nicholas S. Hendren, Jennifer T. Thibodeau Source Type: research

Empagliflozin-A Sodium Glucose Co-transporter-2 Inhibitor: Overview of Its Chemistry, Pharmacology, and Toxicology
CONCLUSION: Empagliflozin is a promising SGLT2 inhibitor that offers an innovative approach to the treatment of type 2 diabetes mellitus. Its unique action mechanism and favorable pharmacokinetic profile contribute to its efficacy in improving glycemic control and reducing cardiovascular risks. While the drug's safety profile is generally favorable, clinicians should be aware of potential adverse effects and monitor patients closely. More study is required to determine the longterm safety and explore potential benefits in other patient populations. Overall, empagliflozin represents a valuable addition to the armamentarium ...
Source: Current Diabetes Reviews - January 24, 2024 Category: Endocrinology Authors: Jyoti Yadav Farogh Ahsan Prabhudatta Panda Tarique Mahmood Vaseem Ahamad Ansari Arshiya Shamim Source Type: research

Early changes in estimated glomerular filtration rate post ‐initiation of empagliflozin in EMPEROR‐Preserved
ConclusionAn initial relatively small eGFR decrease may be expected after empagliflozin initiation. Such small eGFR decrease was not associated with adverse cardiovascular outcomes with empagliflozin. In contrast, eGFR decrease was associated with poor cardiovascular outcomes with placebo. (Source: European Journal of Heart Failure)
Source: European Journal of Heart Failure - January 22, 2024 Category: Cardiology Authors: Tripti Rastogi, Jo ão Pedro Ferreira, Javed Butler, Bettina Johanna Kraus, Michaela Mattheus, Martina Brueckmann, Gerasimos Filippatos, Christoph Wanner, Stuart J. Pocock, Milton Packer, Stefan D. Anker, Faiez Zannad Tags: Research Article Source Type: research