The Current Drug Treatment Landscape for Diabetes and Perspectives for the Future

Abstract

The escalating global epidemic of type 2 diabetes mellitus has focused attention on the devastating consequences of protracted hyperglycemia. Early and effective intervention to control blood glucose is a fundamental principle of treatment guidelines, requiring assiduous use of current therapies. However, many patients do not achieve or maintain glycemic targets, emphasizing the need for further therapies. This narrative review assesses the available medicinal options to address hyperglycemia and the opportunities to develop novel agents.

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

“…During treatment, the gut is exposed to high concentrations of metformin 42 , which interrupt the mitochondrial respiratory chain at complex I, and increase glucose utilization, anaerobic glycolysis and lactate production; some of the lactate can be converted back to glucose in the liver 43 . Lactate-glucose turn over causes energy dissipation, which might contribute to the weight neutrality (lack of weight gain or weight loss) observed in metformin-treated patients 28,42 . In the liver, metformin increases insulin signalling, reduces glucagon action and reduces gluconeogenesis and glyco genolysis 28 .…”

“…Lactate-glucose turn over causes energy dissipation, which might contribute to the weight neutrality (lack of weight gain or weight loss) observed in metformin-treated patients 28,42 . In the liver, metformin increases insulin signalling, reduces glucagon action and reduces gluconeogenesis and glyco genolysis 28 . Metformin can inhibit the mitochondrial redox shuttle enzyme glycerol-3-phosphate dehydrogenase, altering the hepatocellular redox state and resulting in reductions in the ATP:AMP ratio, hepatic gluconeogenesis and the conversion of lactate and glycerol to glucose, and activation of AMP-activated protein kinase (AMPK) 44 .…”

“…Metformin enters cells mainly via solute carrier family 22 member 1 (also known as organic cation transporter 1 (hOCT1)) and exerts multiple insulindependent and insulin-independent actions according to the level of drug exposure and the control of nutrient metabolism within different tissues 28,37,[40][41][42] (FIG. 2).…”

“…The treatment needs of patients with T2DM, and the responses to treatments, are highly variable, reflecting the complexity and variability of the pathogenic process 28,29 , so decisions must be made for each patient regarding the choice of therapy and glycaemic targets. Factors for consideration include patient age, weight, duration of T2DM, risk of hypoglycaemia, cardiovascular risk, concomitant treatments, presence of complications and concomitant life-limiting illness.…”

A New Road for Treating the Vascular Complications of Diabetes: So Let's Step on the Gas

“…In response to the enormity of this medical problem, there have been major initiatives on the part of global health organizations, national diabetes associations, and primary caregivers to educate patients about the benefits of appropriate nutrition and physical activity. For individuals with diabetes who have insufficient appropriate nutrition and physical activity, an increasing number of oral and injectable interventions are available to improve glycemic control (3,4). For many patients, however, the current forms of therapy now used for treating both types of diabetes are inadequate.…”