Dorzagliatin (HMS5552), a novel dual-acting glucokinase activator, improves glycaemic control and pancreatic β-cell function in patients with type 2 diabetes: A 28-day treatment study using biomarker-guided patient selection

Type 2 diabetes (T2DM) is one of the most serious global health problems and is mainly a result of the drastic increase in East Asia, which includes over a fourth of the global diabetes population. Lifestyle factors and ethnicity are two determinants in the etiology of T2DM, and lifestyle changes such as higher fat intake and less physical activity link readily to T2DM in East Asians. It is widely recognized that T2DM in East Asians is characterized primarily by β cell dysfunction, which is evident immediately after ingestion of glucose or meal, and less adiposity compared to the disease in Caucasians. These pathophysiological differences have an important impact on therapeutic approaches. Here, we revisit the pathogenesis of T2DM in light of β cell dysfunction versus insulin resistance in East Asians and discuss ethnic differences in the contributions of insulin secretion and insulin resistance, together with incretin secretin and action, to glucose intolerance.

Glucokinase, a unique isoform of the hexokinase enzymes, which are known to phosphorylate D-glucose and other hexoses, was identified during the past three to four decades as a new, promising drug target for type 2 diabetes. Glucokinase serves as a glucose sensor of the insulin-producing pancreatic islet beta-cells, controls the conversion of glucose to glycogen in the liver and regulates hepatic glucose production. Guided by this fundamental knowledge, several glucokinase activators are now being developed, and have so far been shown to lower blood glucose in several animal models of type 2 diabetes and in initial trials in humans with the disease. Here, the scientific basis and current status of this new approach to diabetes therapy are discussed.

Type 2 diabetes (T2DM) is a leading cause of morbidity and mortality worldwide and a major economic burden. The prevalence of T2DM is rising, suggesting more effective prevention and treatment strategies are necessary. The aim of this narrative review is to summarize the pharmacologic treatment options available for patients with T2DM. Each therapeutic class is presented in detail, outlining medication effects, side effects, glycemic control, effect on weight, indications and contraindications, and use in selected populations (heart failure, renal insufficiency, obesity and the elderly). We also present representative cost for each antidiabetic category. Then, we provide an individualized guide for initiation and intensification of treatment and discuss the considerations and rationale for an individualized glycemic goal.