A fast increasing number of innovative products for the treatment of type 2 diabetes have entered clinical practice and offer new therapeutic approaches for the treatment of type 2 diabetes mellitus. Many more compounds are in clinical trials aiming to hit the market in the future. In addition to control blood glucose, new molecules address specific pathways in the underlying pathophysiology of the disease (figure 1).
Figure 1: Pharmacological approaches to address the pathophysiology of type 2 diabetes mellitus
ADA and the EASD publish a new position statement for the treatment of type 2 diabetes
Many new pathways are the topic of clinical research and will further increase the opportunities to interfere in the pathology of diabetes and diabetic complications. There are high expectations that these new drugs do not only improve blood glucose but more specifically address the nature of obesity, inflammation, and type 2 diabetes. The fast increasing number of new drugs enriches the therapeutic armamentarium but leave a challenge to identify the most beneficial drug or drug combination for an individual patient. Therefore, a better stratification of our diabetic patients is deemed necessary to guide to the most beneficial pharmacological intervention. The ADA and the EASD published a new position statement guiding through the treatment of type 2 diabetes which covers all available blood glucose lowering drugs like Metformin, Sulfonylureas, PPAR-gamma agonists, DPP-IV inhibitors, SGLT-2 inhibitors, GLP-1 agonists, and different insulin strategies.
Further clinical markers are needed to guide individualized treatment
Even though these recommendations provide an important clinical guideline it still leaves a broad gap for individual treatment decisions. Increasing numbers of new treatments create a substantial need to identify robust clinical markers which enable to direct to therapeutic decisions with regard to the most beneficial pharmacological intervention. Beside general clinical characteristics like body weight, body constitution, duration of the disease, or co morbidities, additional treatment predictors are warranted to guide to reasonable pharmacological intervention. There is increasing ongoing research trying to identify a panel of laboratory markers that might help to stratify the pathophysiology of the disease on an individual level, thereby offering a better rationale for drug intervention and pharmacological escalation in an individual patient.
Adipose tissue is a major driver in the development and progression of type 2 diabetes mellitus, lipid disorder and atherogenesis. Several adipokines released from the visceral adipose tissue contribute to the development of insulin resistance, hypertension, lipid disorders, and the activation of inflammation in the vessel wall. Adiponectin is a 244- amino acid protein synthesized solely in adipose tissue, which has been proposed to play an important role in the regulation of energy homeostasis and insulin sensitivity. Chronic inflammation is another feature of type 2 diabetes mellitus, which was found in association with an increased visceral body fat mass. Several inflammatory markers like interleukins, high sensitive reactive peptide etc. are key drivers in the development of insulin resistance and atherogenesis and might serve for better characterization of the disease. Another important component in the progression from obesity and insulin resistance to the manifestation of type 2 diabetes mellitus is dysregulation of alpha and beta cell activity in the Langerhans islets of the pancreas. In type 2 diabetes, glucagon secretion from the alpha cell is increased, especially after food intake, while beta cells fail to cover for the increased insulin demand caused by increasing insulin resistance. The precursor molecule of insulin, intact proinsulin, was identified as a potent marker for the prediction of beta cell failure and progression of the disease. Proinsulin binds to the insulin receptor in a much lower affinity than insulin, but otherwise evolves pro-atherogenic effects by interacting with endothelial cells and increasing coagulation pathways. A panel of laboratory markers might add information to better characterize an individual patient, and thereby would help to identify most beneficial pharmacological intervention based on the individual pathophysiology of a single patient. Pharmacological treatment in type 2 diabetes mellitus should not solely address elevated glucose levels, but should rather consider the complexity of this multi-factorial disease. Beside blood glucose control, body weight, lipids, and blood pressure, the identification of valuable laboratory markers might become an important instrument for guiding treatment escalation in an individual with type 2 diabetes mellitus.