COMBINATION OF EMPAGLIFLOZIN AND LINAGLIPTIN: NOVEL AGENTS FOR MANAGING DIABETIC KIDNEY

Abstract

The number of patients with type 2 diabetes is rapidly increasing, and type 2 diabetes is one of the most common chronic diseases. Diabetic kidney disease (DKD) is among the most important complications of diabetes and often leads to the need for renal replacement therapy, including dialysis and renal replacement¹. Thus, patients with diabetes represent a significant global health burden. The increasing incidence and prevalence of DKD places significant health burdens on patients and costs on our already stressed healthcare system². The Diabetes Control and Complications Trial (DCCT), performed in patients with type 1 diabetes, and the United Kingdom Prospective Diabetes Study (UKPDS), in patients with type 2 diabetes, revealed that intensive glycemic control might inhibit the progression of DKD. Thus, hyperglycemia could be a major factor in the progression of DKD. However, DKD develops despite good glycemic control. Thus, novel therapeutic agents beyond those for glycemic control in patients with DKD are needed¹. There are about 200 million people in the world with DKD in different stages, and hypertension, arteriosclerosis and diabetes mellitus are responsible for over 50% of end-stage renal disease. About 40% of patients with (diagnosed or not) diabetes mellitus has an advanced stage of kidney disease, often because of serious deficiencies in the management of the disease itself. In patients with diabetes mellitus, kidney disease occurs and often develops insidiously; the main renal dysfunctions are due to the thickening of the glomerular basement membranes, the formation of microaneurysms and the development of mesangial nodules³. The onset of a clinically documented diabetic nephropathy is generally preceded by the appearance of proteinuria greater than 500 mg/day⁴. Conventional therapies used in patients with type 2 diabetes mellitus include medications such as metformin, sulphonylureas, thiazolidinediones, meglitinides, and insulin. Except for pioglitazone, which is a thiazolidinedione, all other drugs require dose adjustments and an immediate suspension in patients with a reduction in the glomerular filtration rate (eGFR). In these cases, in fact, there is the risk of development of lactic acidosis (metformin) or hypoglycaemic episodes (sulfonylureas, meglitinides, and insulin)³.