Pharmacological treatment of hyperglycemia in type 2 diabetes

Abstract

Diabetes mellitus is a major public health problem, affecting about 10% of the population (1). Chronic complications of diabetes cause enormous human suffering, including blindness, kidney failure, amputations, myocardial infarction, and stroke. Inspired by the desire to develop better therapies, many researchers have investigated the pathophysiology of type 2 diabetes (T2D). While type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-secreting β cells of the pancreas, T2D is often associated with obesity and is characterized by both impaired insulin secretion and insulin resistance (2). T2D is a progressive disease. Insulin resistance manifests early in the natural history prior to occurrence of overt hyperglycemia. So long as pancreatic β cells secrete sufficient insulin to compensate for insulin resistance, glucose levels are maintained at relatively normal levels (3). Overt diabetes occurs when β cells no longer secrete sufficient insulin to maintain normoglycemia. Fasting hyperglycemia is driven by increased hepatic glucose production due to relatively low insulin levels combined with hepatic insulin resistance. Severity of metabolic defects increases over time, primarily because of increasingly severe impairment in insulin secretion. This Review will discuss the state of the art in pharmacotherapy of T2D. Treatment aims to prevent or delay occurrence of microvascular and macrovascular complications -the main causes of morbidity and mortality in T2D. We focus specifically on hemoglobin A 1c -lowering (HbA1c-lowering) drugs, although antihypertensives, lipid-lowering drugs, optimal nutrition, and physical exercise also contribute to a holistic approach to treatment.

Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis

“…The hazard ratio for all-cause mortality in DKD patients with macroalbuminuria is reported to be 1.83, compared to 1.46 for patients with normoalbuminuria [ 7 ]. Overall, a complex interplay between metabolic processes, epigenetic and nonepigenetic mechanisms, and transcriptional regulation is involved in the development and progression of DKD, and only in the last few years have potential drugs been identified, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors that can act effectively against hypoglycemia and improve kidney outcomes [ 8 , 9 ]. In addition, endothelin-1 (ET-1) has been associated with vasoconstriction, kidney injury, mesangial hyperplasia, glomerulosclerosis, fibrosis, and inflammation, and thus endothelin receptor antagonists have been proposed as potential treatments for DKD [ 10 ].…”

Aspulvinones Suppress Postprandial Hyperglycemia as Potent α-Glucosidase Inhibitors From Aspergillus terreus ASM-1

“…The high prevalence of diabetes has focalized much efforts for novel therapeutic alternatives (Ghosh et al, 2016). Nowadays, alleviating postprandial hyperglycemia is one of the first-line therapeutical strategies for the treatment of diabetes and its complications (Taylor et al, 2021). α-Glucosidase inhibitors (AGIs), such as acarbose, miglitol, and voglibose, are usually employed for controlling postprandial blood glucose levels by delaying the intestinal digestion of carbohydrates (Hossain et al, 2020).…”

Biomimetics provides lessons from nature for contemporary ways to improve human health

“…It was recently reported that wood frogs adapt to low-temperature stress via activation of Nrf2 and increased antioxidant defences [52]. In several recent large double-blind randomised trials, it has been demonstrated that substantial loss of glucose and sodium due to inhibition of sodium-glucose co-transporter 2 (SGLT2) has a major beneficial impact on the progression of kidney disease, major adverse cardiovascular events and hospitalisation due to heart failure and cardiovascular mortality [53]. Patients on SGLT2 inhibitor therapy adjust to the reduction in energy availability and conserve water.…”