Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights

Aparajita Sarkar,1 Kareem Imad Fanous,1 Isra Marei,2 Hong Ding,2 Moncef Ladjimi,3 Ross MacDonald,4 Morley D Hollenberg,5 Todd J Anderson,6 Michael A Hill,7 Chris R Triggle2 1Department of Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar; 2Department of Pharmacology & Medical Education, Weill Cornell Medicine- Qatar, Doha, Qatar; 3Department of Biochemistry & Medical Education, Weill Cornell Medicine-Qatar, Doha, Qatar; 4Health Sciences Library, Weill Cornell Medicine-Qatar, Doha, Qatar; 5Department of Physiology & Pharmacology, and Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 6Department of Cardiac Sciences and Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 7Dalton Cardiovascular Research Center & Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USACorrespondence: Aparajita Sarkar; Chris R Triggle, Email [email protected]; [email protected]: Metformin is an orally effective anti-hyperglycemic drug that despite being introduced over 60 years ago is still utilized by an estimated 120 to 150 million people worldwide for the treatment of type 2 diabetes (T2D). Metformin is used off-label for the treatment of polycystic ovary syndrome (PCOS) and for pre-diabetes and weight loss. Metformin is a safe, inexpensive drug with side effects mostly limited to gastrointestinal issues. Prospective clinical data from the United Kingdom Prospective Diabetes Study (UKPDS), completed in 1998, demonstrated that metformin not only has excellent therapeutic efficacy as an anti-diabetes drug but also that good glycemic control reduced the risk of micro- and macro-vascular complications, especially in obese patients and thereby reduced the risk of diabetes-associated cardiovascular disease (CVD). Based on a long history of clinical use and an excellent safety record metformin has been investigated to be repurposed for numerous other diseases including as an anti-aging agent, Alzheimer’s disease and other dementias, cancer, COVID-19 and also atrial fibrillation (AF). AF is the most frequently diagnosed cardiac arrythmia and its prevalence is increasing globally as the population ages. The argument for repurposing metformin for AF is based on a combination of retrospective clinical data and in vivo and in vitro pre-clinical laboratory studies. In this review, we critically evaluate the evidence that metformin has cardioprotective actions and assess whether the clinical and pre-clinical evidence support the use of metformin to reduce the risk and treat AF. Keywords: metformin, atrial fibrillation, AMPK, hyperglycemia, hypoglycemia, cardiac metabolism, cardiovascular protection, atrial remodelin

Ab initio calculations of electronic structure of the BaCs molecule: adiabatic potential energy curves, spectroscopic constants, spin–orbit effect and permanent and transition electric dipole moments

International audienc

Comparative mechanisms of zearalenone and ochratoxin A toxicities on cultured HepG2 cells: Is oxidative stress a common process?

International audienc

Antidiarrheal and antioxidant activities of Ajuga iva (L.) leave extract

We studied the effect of Ajuga iva leaves extract (AIE) on the intestinal absorption, motricity and its antioxidant capacity against diarrhea. Wistar rats were divided and received either: castor oil (CO), CO and loperamide or CO and different doses of AIE. AIE prevented dose-dependently CO-induced diarrhea. AIE at 800 mg/kg showed inhibition efficiency on defecation and diarrhea. The pro-oxidant effect of the CO in the small intestine was inhibited significantly in presence of AIE: increasing glutathione peroxidase (GPx) activity and lowering oxygen free radicals (OH°, O2°-), carbonyl protein and malondialdehyde (MDA) levels. However, co-administration of AIE in castor oil-exposed groups significantly increased the intestinal contents of calcium and magnesium. AIE exhibits significant anti-diarrheal activity, related in part to its antioxidant properties. Our investigation also provides experimental evidence for the traditional use of this medicinal plant in the treatment of diarrhea