A review of phenformin, metformin, and imeglimin.

Diabetes mellitus is a serious metabolic disorder affecting millions of people worldwide. Phenformin and metformin are biguanide antidiabetic agents that are conveniently synthesized in a single-step chemical reaction. Phenformin was once used to lower blood glucose levels, but later withdrawn from the market in several countries because it was frequently associated with lactic acidosis. Metformin is still a widely prescribed medication for the treatment of type 2 diabetes despite the introduction of several newer antidiabetic agents. Metformin is administered orally and has desirable pharmacokinetics. Incidence of metformin-induced lactic acidosis is serious but very rare. Imeglimin, a novel molecule being investigated by Poxel and Sumitomo Dainippon Pharma in Japan, is currently in clinical trials for the treatment of type 2 diabetes. Unlike metformin, imeglimin is a cyclic molecule containing a triazine ring. However, like metformin, imeglimin is also a basic small molecule. Imeglimin is synthesized from metformin as a precursor via a single step chemical reaction. Recent mechanism of action studies suggests that imeglimin improves mitochondria function, when given in combination with metformin it helps achieve better glycemic control in patients with type 2 diabetes. We herein describe and compare the current status, synthesis, physicochemical properties, pharmacokinetic parameters, mechanism of action, and preclinical/clinical studies of metformin and imeglimin.

Risky Business: Judging the Use of Non-Vitamin K Antagonist Oral Anticoagulants for Non-Valvular Atrial Fibrillation in Patients with Renal Dysfunction.

Warfarin, for many years, was the only oral anticoagulant availablt on the market for the prevention of stroke in patients with atrial fibrillation. Despite being safe and effective, warfarin's medication and food interactions, along with its requirement for frequent monitoring, make it ltss ideal in some patient populations. More recently, non-vitamin K oral antagonists (NOACs) have emergtd as an appealing option as they have fewer medication interactions, do not have food interactions and do not require frequent monitoring. However, patients with a creatinine cltarance (CrCl) of ltss than 30 mL/min were excluded in original drug trials for these agtnts. ltaving providers without certainty that these agtnts can be used safely and effectively in patients with renal dysfunction. This review article will summarize the current availablt data on the use of NOACs for the prevention of stroke in atrial fibrillation patients with renal dysfunction.