Type 2 diabetes is a syndrome characterized by relative insulin deficiency, insulin resistance and increased hepatic glucose output. Medications used to treat the disease are designed to correct one or more of these metabolic abnormalities. Current recommendations of the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) include diet and exercise as first-line therapy plus hypoglycemic drugs. Actually there are seven distinct classes of anti-hyperglicemic agents, each of them displaying unique pharmacologic properties. The aim of this review is to describe the pathophysiological basis of their mechanism of action, a necessary step to individualize treatment of diabetic people, taking into proper consideration potential benefits and secondary effects of drugs. Full article

A variety of treatment modalities exist for individuals with type 2 diabetes mellitus (T2D). In addition to dietary and physical activity interventions, T2D is also treated pharmacologically with nine major classes of approved drugs. These medications include insulin and its analogues, sulfonylureas, biguanides, thiazolidinediones (TZDs), meglitinides, α-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipeptidyl peptidase 4 (DPP4) inhibitors. Pharmacological treatment strategies for T2D are typically based on efficacy, yet favorable responses to such therapeutics are oftentimes variable and difficult to predict. Characterization of drug response is expected to substantially enhance our ability to provide patients with the most effective treatment strategy given their individual backgrounds, yet pharmacogenetic study of diabetes medications is still in its infancy. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs. Here, we provide a comprehensive review of pharmacogenetics investigations of these specific anti-diabetes medications. We focus not only on the results of these studies, but also on how experimental design, study sample issues, and definition of ‘response’ can significantly impact our interpretation of findings. Understanding the pharmacogenetics of anti-diabetes medications will provide critical baseline information for the development and implementation of genetic screening into therapeutic decision making, and lay the foundation for “individualized medicine” for patients with T2D. Full article

Exenatide is a GLP-1 (glucagon-like peptide-1) agonist that has been approved in the UK for use in the management of Type 2 Diabetes Mellitus (T2DM) since 2006. It acts by increasing glucose-induced insulin release and by reducing glucagon secretion postprandially. It therefore increases insulin secretion and reduces glucose levels, especially postprandially. It also reduces gastric emptying and acts centrally to promote satiety. In clinical practice it reduces HbA1c (range; -0.4% to -1.3%), fasting and postprandial blood glucose levels and is the only antidiabetic agent (together with liraglutide; a human GLP-1 analogue) to promote weight loss (range; -1.5 kg to -5.5 kg). It can be used as monotherapy or in combination with metformin and/or sulphonylureas (SU) and/or thiazolinediones (TZD). When compared with insulin it causes similar reductions in HbA1c and glucose levels, but unlike insulin it has the advantage of inducing weight loss. Its main side effect is gastrointestinal (GI) disturbances; nausea is the commonest GI adverse effect, albeit usually mild and transient. Hypoglycaemia is uncommon, especially when used as monotherapy or in combination with metformin. In this review article we scrutinize the currently available evidence for use of exenatide in the management of T2DM. Full article

Although advances have been achieved in the management of type 2 diabetes, current treatment options for patients with this disease still fail to address disease progression, glycaemic control remains suboptimal and therapies are often associated with weight gain and hypoglycaemia. Thus, new antidiabetes therapies are being sought. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones that have been the recent focus of research. The physiological action of GLP-1, in particular, has demonstrated its potential in addressing the therapeutic needs of patients with type 2 diabetes. To exploit this action, liraglutide, a human GLP-1 analogue that shares 97% of its amino acid sequence identity with native GLP-1, has been developed. In a recent phase 3 trial programme (LEAD, Liraglutide Effect and Action in Diabetes), treatment with liraglutide was associated with substantial improvements in glycaemic control and low risk of hypoglycaemia. In addition, reductions in weight and systolic blood pressure were reported. There is also an indication that liraglutide is capable of improving β-cell function and increasing β-cell mass. Thus, liraglutide may overcome the limitations with current therapies and help to address the unmet clinical needs of patients with type 2 diabetes. Full article