Scott R. Drab

Incretin-based therapies for type 2 diabetes mellitus: current status and future prospects.

Incretin‐based therapies encompass two new classes of antidiabetic drugs: glucagon‐like peptide‐1 (GLP‐l) receptor agonists (e.g., liraglutide, exenatide, and exenatide long‐acting release), which are structurally related to GLP‐l, and the dipeptidyl peptidase‐4 (DPP‐4) inhibitors (e.g., sitagliptin and saxagliptin), which limit the breakdown of endogenous GLP‐l. To evaluate the safety and effectiveness of incretin‐based therapies for the treatment of type 2 diabetes mellitus and the role of these therapies in clinical practice, a MEDLINE search (January 1985‐November 2009) was conducted. Relevant references from the publications identified were also reviewed. Of 28 studies identified, 22 were randomized controlled trials. Data show that these therapies affect insulin secretion in a glucose‐dependent manner, achieving clinically meaningful reductions in hemoglobin A1c levels, with very low rates of hypoglycemia. In addition, reductions in body weight have been observed with GLP‐l receptor agonists, which also exert a pronounced effect on systolic blood pressure. Various human and animal studies show that GLP‐l improves β‐cell function and increases β‐cell proliferation in vitro, which may slow disease progression. Thus, incretin‐based therapies represent a promising addition to the available treatments for type 2 diabetes.

Clinical Studies of Liraglutide, a Novel, Once-Daily Human Glucagon-Like Peptide-1 Analog for Improved Management of Type 2 Diabetes Mellitus

Liraglutide, a new glucagon‐like peptide‐1 (GLP‐1)‐receptor agonist with 97% homology to human GLP‐1, can be administered once/day independent of meals in patients with type 2 diabetes mellitus. Clinical trials have demonstrated its efficacy in controlling hyperglycemia, helping patients achieve hemoglobin A1c level goals; in facilitating weight loss, and in improving indexes of β‐cell function when used alone or in combination with metformin, glimepiride, or rosiglitazone. These studies also suggest that liraglutide may be associated with modest improvements in systolic blood pressure. Data from a comparative trial of liraglutide and insulin glargine have suggested that liraglutide provides greater glycemic control with less weight gain, and another study demonstrated that liraglutide provides greater improvements in glycemic control with less hypoglycemia than exenatide and with comparable weight loss. Although liraglutide is well tolerated and is associated with low rates of hypoglycemia, transient and mild nausea can occur when therapy is initiated. However, rates of hypoglycemia appear to be lower and nausea appears to be less persistent with liraglutide than with exenatide. Even though data on the long‐term use of liraglutide are still needed, this drug may provide a useful treatment option in patients poorly controlled with dietary modification and exercise and in those whose diabetes is inadequately controlled by oral antidiabetic agents.

A New Option for Glycemic Control: Insulin Degludec, a New-Generation Basal Insulin with an Ultralong Duration of Action

Basal insulin represents an essential tool in the treatment of diabetes mellitus; it can be prescribed with oral antidiabetic agents for the management of type 2 diabetes (T2D) or used as part of a basal‐bolus regimen in type 1 diabetes (T1D) and more advanced T2D. The basal insulin products currently on the market, although improved, do not optimally mimic endogenous insulin secretion. It is therefore important to investigate how the action of a basal insulin can be improved to match the physiologic profile more precisely and consequently to examine the desired properties of an ideal new‐generation basal insulin. Some of these characteristics would include stable pharmacokinetic (PK) and pharmacodynamic (PD) profiles, true 24‐hour duration of action in all patients, low within‐person variability in absorption and glucose‐lowering action, more flexible dose timing, and low occurrence of hypoglycemia. A new‐generation basal insulin, insulin degludec, currently approved in Japan, Mexico, and Europe, was designed to provide a more stable pharmacotherapeutic option with a lower risk of hypoglycemia than the currently available basal insulins while retaining an efficacious profile. The characteristics of an ideal basal insulin are reviewed, and the pharmacology and clinical attributes of insulin degludec are discussed.

Translating clinical guidelines into clinical practice: Role of the pharmacist in type 2 diabetes management

OBJECTIVES To examine the American Diabetes Association (ADA) and American College of Endocrinology (ACE)/American Association of Clinical Endocrinologists (AACE) diabetes guidelines and identify key areas for increased pharmacist involvement to allow more effective implementation of target glycemic goals. DATA SOURCES Guidelines issued by ADA and ACE/AACE; PubMed searches were performed to identify additional data. STUDY SELECTION Free text searches were performed to identify recent (2000-2008) therapy reviews in the management of type 2 diabetes, as well as articles on specific issues such as telemedicine, self-measurement of blood glucose, and overcoming barriers to treatment. To explore the role of insulin in managing type 2 diabetes, clinical trials involving insulins and insulin analogs in type 2 diabetes were identified using a PubMed search with the Mesh terms insulin or analogs and derivatives plus diabetes mellitus, type 2 and restricted to those published after 2000. The pharmacists role in the treatment of type 2 diabetes was explored in PubMed using the Mesh terms pharmacists[Majr] and diabetes mellitus, type 2/therapy, and free text searches were also performed using the terms patient education, pharmacist, and type 2 diabetes. DATA EXTRACTION By the author. DATA SYNTHESIS The increasing burden of type 2 diabetes highlights the need for tight glycemic control in line with current guidelines and the timely introduction of insulin. Pharmacists have a crucial role in achieving these goals, as they are ideally placed to educate patients about the acceptability of treatment, the importance of self-management, the availability of new technologies and delivery devices, and the need for treatment intensification to achieve glycosylated hemoglobin (A1C) targets. CONCLUSION Pharmacists play a crucial role in helping patients with type 2 diabetes achieve the A1C targets recommended by ADA and ACE/AACE and thereby improve their long-term health.

GLP1-RA Add-on Therapy in Patients with Type 2 Diabetes Currently on a Bolus Containing Insulin Regimen.

Adding glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) to basal insulin regimens has become a guideline‐recommended treatment option for uncontrolled type 2 diabetes. However, limited data exist to support the use of GLP‐1 RAs with insulin regimens, including bolus insulin in patients with type 2 diabetes. The primary objectives of this review were to identify if the combination of a GLP‐1 RA and an insulin regimen containing bolus insulin resulted in improvements in HbA1c, weight loss, reduction in insulin doses, and to evaluate the side effect profile of this combination in terms of nausea and hypoglycemia risk. Eight studies using exenatide twice/day, liraglutide, and dulaglutide were reviewed ranging in average duration of follow‐up from 3 to 15 months. Seven studies showed that addition of a GLP‐1 RA was associated with significant HbA1c reductions ranging from 0.4% to 1.64% from baseline to follow‐up. Patients in all eight studies had significant weight loss in the GLP‐1 RA arm from baseline to follow‐up ranging from 0.87 to 10.2 kg. In all the studies, total daily bolus insulin doses decreased 25–67% from baseline to follow‐up. In some studies, a portion of patients were able to discontinue bolus insulin all together after initiation of a GLP‐1 RA. In addition, in two randomized trials included in the review, the GLP‐1 RA arm showed significant improvement in HbA1c and weight compared with the control group who received basal/bolus regimens. Nausea was identified in 7–42% of participants using GLP‐1 RAs with insulin. Data support the use of GLP‐1 RAs added to insulin regimens already containing bolus insulin for glycemic control, weight loss, and reduction or discontinuation of bolus insulin.

The Evolving Role of the Diabetes Educator

Abstract:The roles of the diabetes educator (DE) have expanded significantly from the basic instruction on self-care on which the profession was established and now encompass a range of key responsibilities within diabetes care. A major focus of recent literature has been evaluation of the effectiveness of diabetes self-management education for such factors as reducing the incidence of diabetes, improving clinical parameters and improving medication adherence. This review describes how DEs and diabetes educational services have impacted patient health, how the role of the DE has changed in the past decade and what roles these professionals may serve in the evolving paradigm of primary care for patients with diabetes. Looking forward, the integration of DEs into coordinated care teams will likely increase to meet the challenges associated with providing quality care to a rapidly expanding population with type 2 diabetes.