Wesley Nuffer

GLP-1 receptor agonists: a review of head-to-head clinical studies.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are attractive options for the treatment of type 2 diabetes (T2D) because they effectively lower A1C and weight while having a low risk of hypoglycemia. The GLP-1 RA class has grown in the last decade with several agents available for use in the US and Europe and several more in development. Since the efficacy and tolerability, dosing frequency, administration requirements, and cost may vary between agents within the class, each agent may offer unique advantages and disadvantages. Through a review of phase III clinical programs for exenatide twice daily, exenatide once weekly, liraglutide, albiglutide, lixisenatide, and dulaglutide, eight head-to-head trials have evaluated the safety and efficacy of GLP-1 RA active comparators. The purpose of this review is to provide an analysis of these trials. The GLP-1 RA head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options at reducing A1C. However, differences exist in terms of magnitude of effect on A1C and weight as well as frequency and severity of adverse effects.

GLP-1 receptor agonists for type 2 diabetes mellitus: recent developments and emerging agents.

More than 26 million people in the United States have type 2 diabetes mellitus (T2D). Many treatment options exist, but achieving long‐term glycemic control in patients with T2D remains challenging. The glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) offer a treatment option that improves glycemic control and reduces weight, with a low risk of hypoglycemia. They have emerged as attractive options for the treatment of T2D, and significant advances and developments continue to be published regarding these agents. To identify relevant literature on emerging issues related to GLP‐1 RAs, a search of the MEDLINE database was performed. Studies published in English evaluating the safety and efficacy of GLP‐1 RAs were analyzed. Because of their advantages and unique mechanism of action, GLP‐1 RAs are currently being studied in new clinical areas, including in combination with basal insulin, as adjunctive therapy in type 1 diabetes, and for weight loss. In addition, there are several emerging agents in development. Lixisenatide is a once‐daily GLP‐1 RA that targets postprandial glucose and may be most useful when added to basal insulin as an alternative to rapid‐acting insulin. Albiglutide and dulaglutide are once‐weekly GLP‐1 RAs that may offer more convenient dosing. The most common adverse effects of all GLP‐1 RA agents are gastrointestinal (e.g., nausea, diarrhea, and vomiting), but the rates of occurrence vary among agents. Due to the differences in pharmacokinetics, efficacy, rates of adverse effects, and administration requirements within the GLP‐1 RA class, each agent should be evaluated independently. The future of GLP‐1 RAs offers broader treatment options for T2D as well as potential in other treatment areas.

Albiglutide A New GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of albiglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in type 2 diabetes (T2D). Data Sources: A MEDLINE search (1950-June 2014) was conducted using the keyword albiglutide. References were reviewed to identify additional sources. Study Selection and Data Extraction: Articles evaluating pharmacokinetics, pharmacodynamics, safety, or efficacy of albiglutide were included. Data Synthesis: Albiglutide is a long-acting GLP-1 RA that lowers glycosylated hemoglobin (A1C) and reduces weight by stimulating glucose-dependent insulin secretion, suppressing glucagon secretion, delaying gastric emptying, and promoting satiety. Albiglutide has a long half-life as a result of resistance to degradation by dipeptidyl peptidase-4 and fusion to albumin, thus allowing once-weekly dosing. Albiglutide has been studied as monotherapy and add-on therapy to metformin, sulfonylureas, thiazolidinediones, insulin glargine, and varying combinations of these agents. Clinical studies have shown albiglutide to be superior to placebo, sitagliptin, and glimepiride and noninferior to insulin glargine and insulin lispro at reducing A1C in T2D patients, with A1C changes from baseline ranging from −0.55% to −0.9%. Noninferiority was not achieved when compared to liraglutide and pioglitazone. Weight changes ranged from +0.28 to −1.21 kg. The most common side effects are upper-respiratory-tract infections, diarrhea, nausea, and injection-site reactions. Conclusion: Albiglutide is the fourth GLP-1 RA approved in the United States. Advantages include once-weekly dosing and fewer gastrointestinal side effects compared with liraglutide, but it is less effective at reducing A1C and weight compared to liraglutide. It has not been compared head to head with other GLP-1 RAs.OBJECTIVE To review the pharmacology, pharmacokinetics, safety, and efficacy of albiglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in type 2 diabetes (T2D). DATA SOURCES A MEDLINE search (1950-June 2014) was conducted using the keyword albiglutide. References were reviewed to identify additional sources. STUDY SELECTION AND DATA EXTRACTION Articles evaluating pharmacokinetics, pharmacodynamics, safety, or efficacy of albiglutide were included. DATA SYNTHESIS Albiglutide is a long-acting GLP-1 RA that lowers glycosylated hemoglobin (A1C) and reduces weight by stimulating glucose-dependent insulin secretion, suppressing glucagon secretion, delaying gastric emptying, and promoting satiety. Albiglutide has a long half-life as a result of resistance to degradation by dipeptidyl peptidase-4 and fusion to albumin, thus allowing once-weekly dosing. Albiglutide has been studied as monotherapy and add-on therapy to metformin, sulfonylureas, thiazolidinediones, insulin glargine, and varying combinations of these agents. Clinical studies have shown albiglutide to be superior to placebo, sitagliptin, and glimepiride and noninferior to insulin glargine and insulin lispro at reducing A1C in T2D patients, with A1C changes from baseline ranging from -0.55% to -0.9%. Noninferiority was not achieved when compared to liraglutide and pioglitazone. Weight changes ranged from +0.28 to -1.21 kg. The most common side effects are upper-respiratory-tract infections, diarrhea, nausea, and injection-site reactions. CONCLUSION Albiglutide is the fourth GLP-1 RA approved in the United States. Advantages include once-weekly dosing and fewer gastrointestinal side effects compared with liraglutide, but it is less effective at reducing A1C and weight compared to liraglutide. It has not been compared head to head with other GLP-1 RAs.

Liraglutide: A New Option for the Treatment of Obesity

Obesity continues to pose a major public health risk to the United States and across the world, with an estimated one‐third of adult Americans being defined as obese. Obesity treatment guidelines recommend the use of pharmacologic therapy in adults who have a body mass index (BMI) of 30 kg/m2 or higher or in patients with a BMI of 27 kg/m2 or higher who have at least one weight‐related comorbid condition (e.g., hypertension, dyslipidemia, insulin resistance, type 2 diabetes mellitus). Liraglutide is a glucagon‐like peptide‐1 receptor agonist that has been successfully used in the treatment of type 2 diabetes for several years. Weight loss has been well described as an additional benefit with liraglutide therapy, which prompted the manufacturer to evaluate and develop a higher dose formulation specifically for the treatment of obesity. Liraglutide 3 mg/day was approved by the U.S. Food and Drug Administration for this indication in December 2014. We performed a search of the Medline database to identify relevant literature focused on liraglutides role specifically in treating obesity. Five clinical trials with this primary end point were identified. Data demonstrated that liraglutide can successfully achieve weight‐loss benchmarks of 5% or more and 10% or more loss from baseline. The most common adverse effects were gastrointestinal and mild to moderate in intensity. The cost of therapy is high, averaging over

Characteristics Valued by the Pharmacy Practice Community When Hiring a Recently Graduated Pharmacist

1000/month for out‐of‐pocket expenses if insurance coverage is not available. Liraglutide is also available for delivery only by subcutaneous injection, which may represent a barrier for patients. Liraglutide 3 mg/day represents another pharmacologic option for the treatment of obesity.

A Comparison of New Pharmacological Agents for the Treatment of Obesity

Objective. To determine those characteristics that are most valued by members of the pharmacy practice community when hiring a new pharmacist. Methods. A survey instrument describing 20 characteristics that a pharmacy graduate may possess was created and sent to pharmacists licensed in Colorado. Respondents were asked to select and prioritize the top 5 characteristics considered most important in hiring a new graduate pharmacist. Responses were segregated by practice (retail vs. institutional) and/or by pharmacist role (manager vs. staff). Results. Three hundred eighteen survey instruments were received. Having good/strong communication skills was the characteristic ranked highest by all groups. Professional behavior and being adaptable were also ranked highly. The characteristics of using the literature and punctuality ranked low overall. Differences were identified in how the groups valued some characteristics. Conclusions. Characteristics preferred in a new pharmacist varied depending on practice site and the managerial responsibilities of the potential employer. Some characteristics, such as communication skills and professional behavior, were considered of high value by all pharmacist groups.

An Interprofessional Education Panel on Development, Implementation, and Assessment Strategies

Objective: To review and compare the phase 3 clinical trial evidence on the 4 new pharmacological agents approved for the management of overweight and obesity. Data Sources: Searches were performed (from 1966 through January 2016) in PubMed/MEDLINE, Scientific Citation Index, and product package inserts to identify key phase 3 clinical trials that were used in the approval of each agent. Study Selection and Data Extraction: Phase 3 clinical trials that listed end points of ≥5% and ≥10% weight loss benchmarks from baseline as well as total percentage of weight loss by participants were selected for the review. Data Synthesis: No head-to-head trials have been identified between these agents at this point, which limits comparisons across agents. Phentermine/topiramate ER appeared to have the best overall average weight loss from baseline as well as highest percentages of patients achieving both ≥5% and ≥10% weight loss benchmarks, followed second by naltrexone/bupropion, and then liraglutide, with lorcaserin showing the lowest rates. Phentermine/topiramate ER completion rates were highest for both treatment and placebo groups, followed by liraglutide, with lorcaserin and naltrexone/bupropion showing similar completion rates, below that of the other 2 agents. Common side effects reported differed between agents, although the most common adverse events reported were gastrointestinal in nature, with liraglutide demonstrating the highest reported rates and lorcaserin demonstrating the lowest. Conclusion: These 4 new pharmacological agents represent new options for the clinician to utilize when trying to manage the problem of obesity. No clear first-line agent has emerged, so treatment decisions should be based on patient-specific factors.

Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Nonglycemic Outcomes in Patients with Type 2 Diabetes

This report provides a primer for implementing interprofessional education (IPE) within pharmacy and health sciences curricula. In 2013, a panel of administrators and faculty members, whose institutions offered IPE, funded by the Josiah Macy Jr. Foundation, shared best collaborative practice models at the American Association of Colleges of Pharmacy (AACP) Annual Meeting. These presenters subsequently collaborated to write a primer as guidance for other institutions interested in successfully implementing and continuously enhancing the quality of IPE programs. In this article, these IPE faculty members provide a rationale for creating IPE reforms, discuss successful strategies for innovative IPE programs, and share lessons learned for implementing effective assessment tools. A structure and process for determining outcomes of IPE models are presented and strategies for exploring shared education opportunities across health professions and for integrating top-down and bottom-up methods for IPE programs are given.

Technosphere Insulin (Afrezza) A New, Inhaled Prandial Insulin

The efficacy of the sodium‐glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin in reducing hyperglycemia in patients with type 2 diabetes is well documented. In addition, positive effects have been observed with these agents on nonglycemic variables, such as reductions in body weight and blood pressure, which may confer additional health benefits. SGLT2 inhibitors are also associated with evidence of renal‐protecting benefits. Furthermore, during the landmark Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA‐REG OUTCOME) trial, a substantial reduction in major adverse cardiovascular outcomes was demonstrated with empagliflozin therapy. In view of the complex pathogenesis of cardiovascular disease in patients with diabetes, a pharmacologic intervention for type 2 diabetes that produces a multifaceted reduction in cardiovascular disease risk, separate from glycemic control alone, would be advantageous. Although SGLT2 inhibitors are generally well tolerated, they are associated with an increased risk of genital mycotic infections, as well as the potential risk for serious adverse events such as dehydration, development of diabetic ketoacidosis, serious urinary tract infections, and bone fractures. The findings of ongoing research will help to determine the magnitude and clinical importance of these adverse events and whether the findings of EMPA‐REG OUTCOME represent a class effect for SGLT2 inhibition or are specific to empagliflozin and will further elucidate the future role of SGLT2 inhibitors in the individualized management of patients with type 2 diabetes. In this article, we discuss the nonglycemic outcomes associated with SGLT2 inhibitor therapy in patients with type 2 diabetes as well as the clinical implications of these agents.

A Three-Year Reflective Writing Program as Part of Introductory Pharmacy Practice Experiences

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of Technosphere insulin (TI), a new inhaled insulin product. Data Sources: Searches were conducted in PubMed/MEDLINE, Scientific Citation Index, and abstracts from both the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) meetings from 2005 to August 2014, utilizing the search terms Afrezza, Technosphere, Afresa, and inhaled insulin. References were reviewed to identify additional sources. Study Selection and Data Extraction: Studies with adequate sample sizes, evaluating clinically relevant end points were included. Data Synthesis: TI is approved by the Food and Drug Administration as a bolus insulin to treat patients with type 1 and type 2 diabetes. Its glucose-lowering properties are less than that of rapid-acting insulins, but it does demonstrate less hypoglycemia. TI’s kinetics make it the fastest absorbed of any insulin available, although its overall onset of action appears similar to insulin lispro. It represents an alternative to bolus injections but would likely be used concomitantly with injected basal insulin. Major adverse effects are respiratory in nature, with cough being the most prominent. There is a small decrease in the forced expiratory volume in 1 s (FEV1) with TI; this appears to be consistent, nonprogressive, and reversible. Patients using TI must receive pulmonary function tests periodically throughout therapy. TI is contraindicated in patients with chronic lung disease and should be used with caution in patients who smoke. Conclusion: TI is a novel inhaled insulin that provides prandial coverage to patients with diabetes, representing an alternative to bolus insulin injections.