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.

Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Clinical Update of Safety and Efficacy.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the treatment of type 2 diabetes mellitus, but consideration of benefits and potential adverse events is required. This review examines the state of glycemic control, weight loss, blood pressure, and tolerability, as well as the current debate about the safety of GLP-1 RAs, including risk of pancreatitis, pancreatic cancer, and thyroid cancer. METHODS: A MEDLINE search (2010-2015) identified publications that discussed longer-acting GLP-1 RAs. Search terms included GLP-1 receptor agonists, liraglutide, exenatide, lixisenatide, semaglutide, dulaglutide, albiglutide, efficacy, safety, pancreatitis, pancreatic cancer, and thyroid cancer. Abstracts from the American Diabetes Association, European Association for the Study of Diabetes, and American Association of Clinical Endocrinologists from 2010 to 2015 were also searched. Efficacy and safety studies, pooled analyses, and meta-analyses were prioritized. RESULTS: Research has confirmed that GLP-1 RAs provide robust glycemic control, weight loss, and blood pressure re-duction. Current studies do not prove increased risk of pancreatitis, pancreatic cancer, or thyroid cancer but more trials are needed since publications that indicate safety or suggest increased risk have methodological flaws that prevent firm conclusions to be drawn about these rare, long-term events. CONCLUSION: GLP-1 RA therapy in the context of individualized, patient-centered care continues to be supported by current literature. GLP-1 RA therapy provides robust glycemic control, blood pressure reduction, and weight loss, but studies are still needed to address concerns about tolerability and safety, including pancreatitis and cancer.

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.

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-1) receptor agonists (e.g., liraglutide, exenatide, and exenatide long-acting release), which are structurally related to GLP-1, and the dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin and saxagliptin), which limit the breakdown of endogenous GLP-1. 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 A(1c) levels, with very low rates of hypoglycemia. In addition, reductions in body weight have been observed with GLP-1 receptor agonists, which also exert a pronounced effect on systolic blood pressure. Various human and animal studies show that GLP-1 improves beta-cell function and increases beta-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 A(1c) level goals; in facilitating weight loss, and in improving indexes of beta-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.

Instructor satisfaction with a technology-based resource for diabetes education.

OBJECTIVES: To evaluate instructor use patterns and satisfaction with DM Educate, a comprehensive, Web-based diabetes course. METHODS: Instructors completed a post-course survey instrument to assess their use of course materials and components, as well as satisfaction with the course content, design, and technology utilized, and to solicit their suggestions for additional content areas. RESULTS: Thirty-eight percent of respondents utilized DM Educate as a standalone elective and 62% had integrated materials into existing courses. The pharmacotherapy module was the most utilized at 91% and slide sets were the most utilized course components at 63%. All instructors stated that they would use the course again the following year. Suggestions for improvement included incorporation of more active-learning activities and patient cases. CONCLUSION: Instructors' were highly satisfied with the course materials and technology used by DM Educate, a Web-based diabetes education course, and indicated they were able to customize the course materials both to establish new courses and supplement existing courses. All instructors planned to use the course again.

Recognizing the rising impact of diabetes in seniors and implications for its management.

OBJECTIVES: To identify the incidence and symptoms of type 2 diabetes in older adult patients, review appropriate glycemic targets for older adults with type 2 diabetes, and consider the rationale for managing hyperglycemia in this patient population. DATA SOURCES: Live symposium presentation based on clinical practice and research, medical literature, and studies published between January 1993 and November 2008 on managing diabetes in older adults, government statistics, and medical society guidelines. STUDY SELECTION: Thirty-five articles were identified from various data sources and were evaluated. The following search terms were used: Complications, Diabetes, Glucose Tolerance, Goals, Hyperglycemic Hyperosmolar Nonketotic Syndrome (HHNS), Long-term Care, Management, Obesity, Prevalence, Risk Factors, Screening, Senior, and Symptoms. All information deemed relevant to recognizing the rising impact of diabetes in seniors and its implications for management were included. DATA EXTRACTION: Data were extracted independently of the author by the librarians of the University of Pittsburgh. DATA SYNTHESIS: As a result of the aging of the U.S. population, the increasing prevalence of diabetes, and the considerable impact of this disease among older adults, it is only logical to assume that the number of older individuals with diabetes and its impact on older adults will continue to rise. Uncontrolled diabetes has significant risks in the elderly beyond the typical microvascular and macrovascular complications commonly associated with diabetes: cognitive impairment, depression, excessive skin problems, and an increased risk of falls. However, glycemic control reduces the development of these complications and can lead to improvements in dementia, memory, energy, physical activity, mood, and quality of life. CONCLUSION: Because many older adults may benefit from intensive, long-term glycemic control, consultant pharmacists should understand the importance of individualizing glycemic targets, management strategies, and pharmacotherapy in older adults.

A Web-based interprofessional diabetes education course.

OBJECTIVE: To develop a comprehensive diabetes management course for pharmacy students that is available to all colleges and schools of pharmacy via the Internet. DESIGN: DM Educate, a Web-based course consisting of 12 topic modules with video lectures, active-learning exercises, and test questions prepared by nationally recognized experts was developed. The modular design allows use as a standalone, 3-credit course or use of individual module content as a supplement to an existing course. ASSESSMENT: Two pilot studies found the comprehensive, interprofessional nature of the material beneficial for learners. Students showed a significant increase in knowledge of the subject material by correctly answering 26 of 34 questions on the posttest compared to answering only 14 of 34 questions correctly on the pretest (p < 0.001). Student feedback was positive for the flexibility of the Web-based format. CONCLUSION: Pilot studies demonstrated the effectiveness of the course, which became available in the 2006-2007 academic year.