review of literature on clinical pancreatology - The Pancreapedia

Diabetic overviewTo provide an overview <strong>of</strong> the disease burden and current strategies in the treatment <strong>of</strong>patients with type 2 diabetes a Medline search <strong>of</strong> all relevant clinical and <strong>review</strong> articles wasdone. The prevalence <strong>of</strong> diabetes in the United States has reached epidemic proportionswith the total diagnosed and undiagnosed cases among people aged 20 years or olderestimated at 13 percent, and it continues to rise at an alarming rate. This upsurge has beenparalleled by an increase in rates <strong>of</strong> obesity. Type 2 diabetes accounts for up to 95 percent<strong>of</strong> diabetes cases and is <strong>of</strong>ten comorbid with hypertension and dyslipidemia. It wasconcluded that tight glycemic control is necessary for the management <strong>of</strong> type 2 diabetes,but progressive deterioration <strong>of</strong> beta-cell function can lead to a loss <strong>of</strong> glycemic control. Oralantidiabetes drugs and insulin are effective but do not always correct the associatedmetabolic and glucoregulatory dysfunctions, and hypoglycemia and weight gain are commonadverse effects <strong>of</strong> these agents. A clear need exists for aggressive therapeutic optionsparticularlyincretin-based agents-that can be combined with existing agents to preservebeta-cell function and halt the progression <strong>of</strong> type 2 diabetes [136].Incretin mimeticsAs a consequence <strong>of</strong> excess abdominal adiposity and genetic predisposition, type 2 diabetesis a progressive disease, <strong>of</strong>ten diagnosed after metabolic dysfunction has taken hold <strong>of</strong>multiple organ systems. Insulin deficiency, insulin resistance and impaired glucosehomeostasis resulting from beta-cell dysfunction characterize the disease. Current treatmentgoals are <strong>of</strong>ten unmet due to insufficient treatment modalities. Even when combined, thesetreatment modalities are frequently limited by safety, tolerability, weight gain, edema andgastrointestinal intolerance. Recently, new therapeutic classes have become available fortreatment. A <strong>review</strong> will examine the new therapeutic classes <strong>of</strong> incretin mimetics andenhancers in the treatment <strong>of</strong> type 2 diabetes [137].A PubMed search was conducted for the years 2000-2009, using as keywords the names <strong>of</strong>glucagon-like peptide-1 (GLP-1) receptor agonists (exenatide and liraglutide) and dipeptidylpeptidase-4 (DPP-4) inhibitors (sitagliptin, alogliptin, and saxagliptin). The author includedrandomized controlled trials <strong>of</strong> incretin therapies that were published in English and enrolled+100 participants. A total <strong>of</strong> 27 randomized controlled studies <strong>of</strong> incretin therapy wereidentified and included in the <strong>review</strong>. GLP-1 receptor agonists and DPP-4 inhibitors wereevaluated at different points in the diabetes treatment spectrum, i.e. added to diet andexercise alone (monotherapy) or added to oral antihyperglycemic regimens (combinationtherapy). In addition to decreasing glycemia in type 2 diabetes, incretin therapies mayimprove other important parameters, including beta-cell function, blood pressure, and lipidlevels, with a low risk for hypoglycemia. A comparison <strong>of</strong> the study data differentiates theclinical pr<strong>of</strong>iles <strong>of</strong> the GLP-1 receptor agonists, which are associated with weight loss, andDPP-4 inhibitors, which are weight neutral, as well as the individual agents within each class[138].Type 2 diabetes mellitus has become an enormous and worldwide healthcare problem that isalmost certain to worsen. Current therapies, which address glycemia and insulin resistance,have not adequately addressed the complications and treatment failures associated with thisdisease. New treatments based on the incretin hormones provide a novel approach toaddress some components <strong>of</strong> the complex pathophysiology <strong>of</strong> type 2 diabetes. The purpose<strong>of</strong> one <strong>review</strong> was to elucidate the science <strong>of</strong> the incretin hormones and describe the incretineffect and its regulatory role in beta-cell function, insulin secretion, and glucose metabolism.The key endogenous hormones <strong>of</strong> incretin system are glucose-dependent insulinotropicpolypeptide (GIP) and glucagon-like peptide-1 (GLP-1); a key enzymatic regulator <strong>of</strong> thesehormones is dipeptidyl peptidase-4, which rapidly inactivates/degrades the incretin